FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Huang, Z Szostak, JW AF Huang, Z Szostak, JW TI Evolution of aptamers with secondary structures from a new specificity and new an ATP aptamer SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE aptamer; specificity; fold; selection; RNA evolution ID RNA APTAMER; MOLECULAR RECOGNITION; GENE-THERAPY; RIBOZYMES; DNA; DISCRIMINATION; SEQUENCES; COMPLEX; SHAPES; MOTIF AB Small changes in target specificity can sometimes be achieved, without changing aptamer structure, through mutation of a few bases. Larger changes in target geometry or chemistry may require more radical changes in an aptamer. In the latter case, it is unknown whether structural and functional solutions can still be found in the region of sequence space close to the original aptamer. To investigate these questions, we designed an in vitro selection experiment aimed at evolving specificity of an ATP aptamer. The ATP aptamer makes contacts with both the nucleobase and the sugar. We used an affinity matrix in which GTP was immobilized through the sugar, thus requiring extensive changes in or loss of sugar contact, as well as changes in recognition of the nucleobase. After just five rounds of selection, the pool was dominated by new aptamers failing into three major classes, each with secondary structures distinct from that of the ATP aptamer. The average sequence identity between the original aptamer and new aptamers is 76%. Most of the mutations appear to play roles either in disrupting the original secondary structure or in forming the new secondary structure or the new recognition loops. Our results show that there are novel structures that recognize a significantly different ligand in the region of sequence space close to the ATP aptamer. These examples of the emergence of novel functions and structures from an RNA molecule with a defined specificity and fold provide a new perspective on the evolutionary flexibility and adaptability of RNA. C1 CUNY Brooklyn Coll, Dept Chem, Grad Sch, PhD Program Chem, Brooklyn, NY 11210 USA. CUNY Brooklyn Coll, Dept Chem, Grad Sch, PhD Program Biochem, Brooklyn, NY 11210 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. RP Huang, Z (reprint author), CUNY Brooklyn Coll, Dept Chem, Grad Sch, PhD Program Chem, Brooklyn, NY 11210 USA. FU NIGMS NIH HHS [GM 53936, R01 GM053936] NR 29 TC 45 Z9 47 U1 3 U2 30 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD DEC PY 2003 VL 9 IS 12 BP 1456 EP 1463 DI 10.1261/rna.5990203 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 745XQ UT WOS:000186716900007 PM 14624002 ER PT J AU Lee, JT AF Lee, JT TI X-chromosome inactivation: a multi-disciplinary approach SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD DEC PY 2003 VL 14 IS 6 BP 311 EP 312 DI 10.1016/j.semcdb.2003.09.025 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 754YE UT WOS:000187360400001 PM 15015737 ER PT J AU Choi, NC AF Choi, NC TI Radioprotective effect of amifostine in radiation pneumonitis SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Cytoprotection Investigators Congress CY MAY 15-18, 2003 CL NEVIS, W IND ASSOC ST ID CELL LUNG-CANCER; RANDOMIZED PHASE-III; THORACIC IRRADIATION; PULMONARY FIBROSIS; NECK-CANCER; STAGE-II; WR-2721; TRIAL; RADIOTHERAPY; MICE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cambridge, MA 02138 USA. RP Choi, NC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 35 TC 8 Z9 8 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2003 VL 30 IS 6 SU 18 BP 10 EP 17 DI 10.1053/j.seminoncol.2003.11.038 PG 8 WC Oncology SC Oncology GA 767DK UT WOS:000188424800003 PM 14727236 ER PT J AU Haddad, R Wirth, L Costello, R Weeks, L Posner, M AF Haddad, R Wirth, L Costello, R Weeks, L Posner, M TI Phase II randomized study of concomitant chemoradiation using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with newly diagnosed locally advanced squamous cell carcinoma of the head and neck SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Cytoprotection Investigators Congress CY MAY 15-18, 2003 CL NEVIS, W IND ASSOC ST ID INDUCTION CHEMOTHERAPY; RADIATION-THERAPY; CANCER; RADIOTHERAPY; TRIAL; DOCETAXEL; CISPLATIN; LARYNGEAL; LIFE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol Head, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Div, Boston, MA 02115 USA. RP Haddad, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol Head, SW430G,44 Binney St, Boston, MA 02115 USA. NR 22 TC 14 Z9 14 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2003 VL 30 IS 6 SU 18 BP 84 EP 88 DI 10.1053/j.seminoncol.2003.11.011 PG 5 WC Oncology SC Oncology GA 767DK UT WOS:000188424800013 PM 14727246 ER PT J AU Winer, EP Shapiro, CL AF Winer, EP Shapiro, CL TI Introduction: Late effects of treatment and surviorship issues in early-stage breast carcinoma SO SEMINARS IN ONCOLOGY LA English DT Editorial Material C1 Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shapiro, CL (reprint author), Ohio State Univ, Med Ctr, 10 N Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2003 VL 30 IS 6 BP 729 EP 729 DI 10.1053/S0093-7754(03)00546-3 PG 1 WC Oncology SC Oncology GA 756KR UT WOS:000187464700001 ER PT J AU Kornblith, AB Ligibel, J AF Kornblith, AB Ligibel, J TI Psychosocial and sexual functioning of survivors of breast cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; POSTTRAUMATIC-STRESS-DISORDER; STANDARD-DOSE CHEMOTHERAPY; PSYCHOLOGICAL DISTRESS; BODY-IMAGE; FOLLOW-UP; SOCIAL SUPPORT; ADJUVANT CHEMOTHERAPY; CONSERVING TREATMENT C1 Dana Farber Canc Inst, Womens Canc Program, Boston, MA 02115 USA. RP Kornblith, AB (reprint author), Dana Farber Canc Inst, Womens Canc Program, Room D1210,44 Binney St, Boston, MA 02115 USA. NR 124 TC 75 Z9 78 U1 1 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2003 VL 30 IS 6 BP 799 EP 813 DI 10.1053/S0093-7754(03)00475-5 PG 15 WC Oncology SC Oncology GA 756KR UT WOS:000187464700008 PM 14663780 ER PT J AU Partridge, AH Winer, EP Burstein, HJ AF Partridge, AH Winer, EP Burstein, HJ TI Follow-up care of breast cancer survivors SO SEMINARS IN ONCOLOGY LA English DT Review ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM COMPLICATIONS; TAMOXIFEN THERAPY; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; CARCINOMA SURVIVORS; RADIATION-THERAPY; UTERINE SARCOMA; ARM MORBIDITY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, 44 Binney St, Boston, MA 02115 USA. NR 88 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2003 VL 30 IS 6 BP 817 EP 825 DI 10.1053/S0093-7754(03)00476-7 PG 9 WC Oncology SC Oncology GA 756KR UT WOS:000187464700010 PM 14663782 ER PT J AU Rifkin, R Mukherjee, S Tamayo, P Ramaswamy, S Yeang, CH Angelo, M Reich, M Poggio, T Lander, ES Golub, TR Mesirov, JP AF Rifkin, R Mukherjee, S Tamayo, P Ramaswamy, S Yeang, CH Angelo, M Reich, M Poggio, T Lander, ES Golub, TR Mesirov, JP TI An analytical method for multiclass molecular cancer classification SO SIAM REVIEW LA English DT Article DE multiclass classification; support vector machine; tumor; molecular classification; pattern recognition; cancer; computational biology ID SUPPORT VECTOR MACHINES; EXPRESSION DATA; SELECTION; MARGIN AB Modern cancer treatment relies upon microscopic tissue examination to classify tumors according to anatomical site of origin. This approach is effective but subjective and variable even among experienced clinicians and pathologists. Recently, DNA microarray-generated gene expression data has been used to build molecular cancer classifiers. Previous work from our group and others demonstrated methods for solving pairwise classification problems using such global gene expression patterns. However, classification across multiple primary tumor classes poses new methodological and computational challenges. In this paper we describe a computational methodology for multiclass prediction that combines class-specific (one vs. all) binary support vector machines. We apply this methodology to the diagnosis of multiple common adult malignancies using DNA microarray data from a collection of 198 tumor samples, spanning 14 of the most common tumor types. Overall classification accuracy is 78%, far exceeding the expected accuracy for random classification. In a large subset of the samples (80%), the algorithm attains 90% accuracy. The methodology described in this paper both demonstrates that accurate gene expression-based multiclass cancer diagnosis is possible and highlights some of the analytic challenges inherent in applying such strategies to biomedical research. C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, McGovern Inst, Ctr Biol & Computat Learning, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. X Mine, Brisbane, CA 94005 USA. RP Rifkin, R (reprint author), MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. OI Mukherjee, Sayan/0000-0002-6715-3920 NR 33 TC 44 Z9 46 U1 0 U2 7 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1445 J9 SIAM REV JI SIAM Rev. PD DEC PY 2003 VL 45 IS 4 BP 706 EP 723 DI 10.1137/S0036144502411986 PG 18 WC Mathematics, Applied SC Mathematics GA 751EE UT WOS:000187039200003 ER PT J AU Stylopoulos, N Rattner, D AF Stylopoulos, N Rattner, D TI Robotics and ergonomics SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID ASSISTED LAPAROSCOPIC SURGERY; ENDOSCOPIC SURGERY; INITIAL EXPERIENCE; INVASIVE SURGERY; DA-VINCI; CHOLECYSTECTOMY; PERFORMANCE; FEASIBILITY; WORKING; SYSTEM AB Surgical robots can significantly enhance the surgeon's dexterity as well as provide an ergonomically efficient and user-friendly working environment. This article gives an overview of the physical, sensory, and cognitive ergonomic issues in robotic surgery. Robotic systems can potentially provide a more efficient tool-tissue interface and an ergonomically-improved and user-friendly hand-tool interface. At the same time robots can expand the natural abilities of humans by providing complementary information (eg, force feedback, enhanced visual feedback). Although robotic systems significantly lower the physical stress and the mental workload that surgeons experience with the conventional surgical instruments, their efficiency and cost-effectiveness remain to be proven. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rattner, D (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. NR 80 TC 38 Z9 40 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD DEC PY 2003 VL 83 IS 6 BP 1321 EP + DI 10.1016/S0039-6109(03)00161-0 PG 18 WC Surgery SC Surgery GA 754LT UT WOS:000187319200006 PM 14712869 ER PT J AU Tunnell, JW Desjardins, AE Galindo, L Georgakoudi, I McGee, SA Mirkovic, J Mueller, MG Nazemi, J Nguyen, FT Wax, A Zhang, QG Dasari, RR Feld, MS AF Tunnell, JW Desjardins, AE Galindo, L Georgakoudi, I McGee, SA Mirkovic, J Mueller, MG Nazemi, J Nguyen, FT Wax, A Zhang, QG Dasari, RR Feld, MS TI Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article ID LIGHT-SCATTERING SPECTROSCOPY; SQUAMOUS INTRAEPITHELIAL LESIONS; IN-VIVO; FLUORESCENCE SPECTROSCOPY; REFLECTANCE SPECTROSCOPY; INTRINSIC FLUORESCENCE; BARRETTS-ESOPHAGUS; BIOLOGICAL TISSUE; TURBID MEDIA; CANCER AB Reflectance and fluorescence spectroscopies have shown great promise for early detection of epithelial dysplasia. We have developed a clinical reflectance spectrofluorimeter for multimodal spectroscopic diagnosis of epithelial dysplasia. This clinical instrument, the FastEEM, collects white light reflectance and fluorescence excitation-emission matrices (EEM's) within a fraction of a second. In this paper we describe the FastEEM instrumentation, designed for collection of multi-modal spectroscopic data. We illustrate its performance using tissue phantoms with well defined optical properties and biochemicals of known fluorescence properties. In addition, we discuss our plans to develop a system that combines a multi-spectral imaging device for wide area surveillance with this contact probe device. C1 MIT, GR Harrison Spect Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Dermatol, Boston, MA 02114 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. RP Feld, MS (reprint author), MIT, GR Harrison Spect Lab, 77 Massachusetts Ave,Bldg 6-014, Cambridge, MA 02139 USA. RI Wax, Adam/A-4760-2008; Nguyen, Freddy/A-2541-2008; Mirkovic, Jelena/A-6253-2013; OI Nguyen, Freddy/0000-0003-0106-8114; Wax, Adam/0000-0002-1827-5112 FU NCI NIH HHS [R01-CA97966]; NCRR NIH HHS [P41-RR02594] NR 33 TC 29 Z9 29 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2003 VL 2 IS 6 BP 505 EP 514 PG 10 WC Oncology SC Oncology GA 759VQ UT WOS:000187757900003 PM 14640762 ER PT J AU Janicek, MJ Demetri, G Janicek, MR Shaffer, K Fauci, MA AF Janicek, MJ Demetri, G Janicek, MR Shaffer, K Fauci, MA TI Dynamic infrared imaging of newly diagnosed malignant lymphoma compared with gallium-67 and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article ID NON-HODGKINS-LYMPHOMA; BREAST-CARCINOMA; SCINTIGRAPHY; PREDICTION; PET; CHEMOTHERAPY; THERMOGRAPHY; DISEASE; CANCER AB Staging and therapy monitoring of malignant lymphomas relies heavily on imaging using arbitrary size criteria from computed tomography (CT) and sometimes non-specific radionuclide studies to assess the activity of the disease. Treatment decisions are based on early assessment of the response to therapy and the residual volume of the disease. Our initial experience is reported using a new noninvasive, inexpensive, and reproducible passive imaging modality, Dynamic Infrared Imaging (DIRI), which may add a new dimension to functional imaging. This system relies on its ability to filter the raw infrared signal using biological oscillatory behavior. It detects and analyzes minute oscillations of temperature and heat distribution in tumors. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiol, Boston, MA 02115 USA. Williams Coll, Williamstown, MA 01267 USA. OmniCorder Technol Inc, E Setauket, NY USA. RP Janicek, MJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiol, Boston, MA 02115 USA. NR 27 TC 5 Z9 8 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2003 VL 2 IS 6 BP 571 EP 577 PG 7 WC Oncology SC Oncology GA 759VQ UT WOS:000187757900009 PM 14640768 ER PT J AU Aravagiri, M Marder, SR Nuechterlein, KH Gitlin, MJ AF Aravagiri, M Marder, SR Nuechterlein, KH Gitlin, MJ TI Intra- and interindividual variations in steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients treated chronically with various doses of risperidone SO THERAPEUTIC DRUG MONITORING LA English DT Article DE risperidone; 9-hydroxyrisperidone; steady-state plasma levels; inter- and intraindividual variations; plasma level monitoring; LC-MS-MS ID SERUM CONCENTRATIONS; ACTIVE METABOLITE; DRUG-INTERACTIONS; PHARMACOKINETICS; RAT; 5-HT2; BRAIN; D-2; ANTIPSYCHOTICS; PROPRANOLOL AB The intra- and interindividual variability in apparent steady-state plasma levels of risperidone (RSP) and its metabolite 9-hydroxyrisperidone (9-OHRSP) in schizophrenic patients was investigated. Patients (n = 46, age 26.4 +/- 5.3 years) with diagnosed schizophrenia were treated with a fixed daily oral dose of RSP (1-12 mg/d). The steady-state plasma samples from these patients were collected over a period of 5 years and a total of 549 visits. Plasma concentrations of RSP and 9-OHRSP were determined using a highly sensitive and specific LC-MS-MS method with a detection limit of 0.1 ng/mL. All plasma samples had measurable amounts of 9-OHRSP; however, RSP was nondetectable (<0.1 ng/mL) in 18% of the plasma samples. 9-OHRSP levels were, on average, similar to22 times higher than those of RSP. The plasma levels of RSP and 9-OHRSP varied widely among patients receiving similar doses of RSP, and the intra- and interindividual variations of RSP and 9-OHRSP plasma levels were found to be large. The data indicated that there was no significant change in the steady-state levels of either RSP or 9-OHRSP during the treatment period. Similarly, the dose-normalized concentration did not vary significantly during the treatment period or with the administered dose. The absence of RSP in many plasma samples (<0.1 ng/mL) and presence of 9-OHRSP at severalfold higher concentrations than RSP indicate that measuring plasma levels of RSP alone may lead to erroneous interpretation in plasma level monitoring studies. The current data support the fact that it is important to measure steady-state levels of total active moiety by analyzing both RSP and 9-OHRSP for plasma drug monitoring. C1 Univ Calif Los Angeles, Psychopharmacol Unit, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90073 USA. RP Aravagiri, M (reprint author), Univ Calif Los Angeles, Psychopharmacol Unit, VA Greater Los Angeles Healthcare Syst, Bldg 210 15,11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. NR 32 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD DEC PY 2003 VL 25 IS 6 BP 657 EP 664 DI 10.1097/00007691-200312000-00003 PG 8 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 747YG UT WOS:000186833500002 PM 14639051 ER PT J AU Aujesky, D Hayoz, D Yersin, B Perrier, A Barghouth, G Schnyder, P Bischof-Delaloye, A Cornuz, J AF Aujesky, D Hayoz, D Yersin, B Perrier, A Barghouth, G Schnyder, P Bischof-Delaloye, A Cornuz, J TI Exclusion of pulmonary embolism using C-reactive protein and D-dimer SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE pulmonary embolism; C-reactive protein; D-dimer; clinical probability assessment ID DEEP VENOUS THROMBOSIS; SIMPLE CLINICAL-MODEL; NONINVASIVE DIAGNOSIS; VEIN THROMBOSIS; THROMBOEMBOLISM; OUTPATIENTS; PERFORMANCE; PROBABILITY; EMERGENCY; PLASMA AB Our goal was to evaluate the diagnostic utility of C-reactive protein (CRP) alone or combined with clinical probability assessment in patients with suspected pulmonary embolism (PE), and to compare its performance to a D-dimer assay. We conducted a prospective study in which we performed a common immuno-turbidimetric CRP test and a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer test in 259 consecutive outpatients with suspected PE at the emergency department of a teaching hospital. We assessed clinical probability of PE by a validated prediction rule overridden by clinical judgment. Patients with D-dimer levels greater than or equal to 500 mug/l underwent a work-up consisting of lower-limb venous ultrasound, spiral computerized tomography, ventilation-perfusion scan, or pulmonary angiography. Patients were followed up for three months. Seventy-seven (30%) of the patients had PE. The CRP alone had a sensitivity of 84% (95% confidence interval [Cl).: 74 to 92%) and a negative predictive value (NPV) of 87% (95% Cl: 78 to 93%) at a cutpoint of 5 mg/l. Overall, 61 (24%) patients with a low clinical probability of PE had a CRP < 5 mg/l. Due to the low prevalence of PE (9%) in this subgroup, the NPV increased to 97% (95% Cl: 89 to 100%). The D-dimer (cutpoint 500 mug/l) showed a sensitivity of 100% (95% Cl: 95 to 100%) and a NPV of 100% (95% Cl: 94 to 100%) irrespective of clinical probability and accurately rule out PE in 56 (22%) patients. Standard CRP tests alone or combined with clinical probability assessment cannot safely exclude PE. C1 Univ Lausanne Hosp, Dept Med, Lausanne, Switzerland. Univ Lausanne Hosp, Div Angiol, Lausanne, Switzerland. Univ Lausanne Hosp, Dept Emergency Med, Lausanne, Switzerland. Univ Lausanne Hosp, Dept Radiol, Lausanne, Switzerland. Univ Lausanne Hosp, Dept Nucl Med, Lausanne, Switzerland. Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland. Univ Hosp Geneva, Dept Med, Geneva, Switzerland. RP Aujesky, D (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,11E127, Pittsburgh, PA 15240 USA. RI Perrier, Arnaud/M-2263-2014 NR 26 TC 15 Z9 17 U1 0 U2 3 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD DEC PY 2003 VL 90 IS 6 BP 1198 EP 1203 DI 10.1160/TH03-03-0175 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 755QW UT WOS:000187422800035 PM 14652657 ER PT J AU Zigman, JM Cohen, SE Garber, JR AF Zigman, JM Cohen, SE Garber, JR TI Impact of thyroxine-binding globulin on thyroid hormone economy during pregnancy SO THYROID LA English DT Article ID TBG DEFICIENCY; INCREASED NEED; HYPOTHYROIDISM; THERAPY; WOMEN; ESTROGEN AB Pregnancy-associated changes in thyroid hormone economy are well-established and are of significant clinical relevance to women with established hypothyroidism because they usually result in increased thyroxine dose requirements by these women. Studies suggest that elevations in serum thyroxine-binding globulin (TBG) have the most influence on this increased need for thyroxine, although the exact contributions by TBG rises and by other mechanisms is as yet unclear. We report the case of a 42-year-old woman, with both established primary hypothyroidism and TBG deficiency, who we have now managed through two full-term pregnancies. The patient was noted to have a baseline TBG that was approximately 30% of the average baseline level reported for non-TBG-deficient individuals. Her TBG levels were induced by pregnancy, although the absolute increase of 1.0 mg/dL was only half the increase usually associated with pregnancy. Despite the patient's low baseline TBG level and her blunted pregnancy-associated TBG induction, her absolute and relative pregnancy-associated increases in thyroxine replacement dosage mirrored those found in non-TBG-deficient, hypothyroid women. Thus, our limited study suggests that an increase in TBG concentration is not the key determinant for the increase in thyroxine requirement in pregnancy. C1 Harvard Univ, Vanguard Med Associates, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Garber, JR (reprint author), Harvard Univ, Vanguard Med Associates, Div Endocrinol, 133 Brookline Ave, Boston, MA 02215 USA. FU NIDDK NIH HHS [5T32DK07516-18] NR 14 TC 6 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 2003 VL 13 IS 12 BP 1169 EP 1175 DI 10.1089/10507250360731587 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760BF UT WOS:000187790100012 PM 14751039 ER PT J AU Berretta, F Butler, RH Diaz, G Sanarico, N Arroyo, J Fraziano, M Aichinger, G Wucherpfennig, KW Colizzi, V Saltini, C Amicosante, M AF Berretta, F Butler, RH Diaz, G Sanarico, N Arroyo, J Fraziano, M Aichinger, G Wucherpfennig, KW Colizzi, V Saltini, C Amicosante, M TI Detailed analysis of the effects of Glu/Lys beta 69 human leukocyte antigen-DP polymorphism on peptide-binding specificity SO TISSUE ANTIGENS LA English DT Article DE binding prediction; HLA-DP; molecular modeling; peptide-binding motif; vaccine design; beta 69 polymorphism ID MHC CLASS-II; VERSUS-HOST DISEASE; HLA-DR MOLECULES; T-CELLS; MARROW TRANSPLANTATION; RHEUMATOID-ARTHRITIS; BERYLLIUM DISEASE; INVARIANT CHAIN; SELF-PEPTIDE; EPITOPES AB The polymorphism at position beta69 of the human leukocyte antigen (HLA)-DP molecule has been associated with susceptibility to several immune disorders and alloreactivity. Using molecular modeling, we have predicted a detailed structure of the HLA-DP2 molecule (carrying Glubeta69) complexed with class II associated invariant chain derived peptide (CLIP) and compared it with the form carrying Lys at beta69 (HLA-DP2K69). Major changes between the two models were observed in the shape and charge distribution of pocket 4 and of the nearby pocket 6. Consequently, we analyzed in detail the peptide-binding specificities of both HLA-DP molecules expressed as recombinant proteins. We first determined that the minimum peptide-binding core of CLIP for both HLA-DP2 and DP2K69 is represented by nine aminoacids corresponding to the sequence 91-99 of invariant chain (Ii). We then assessed the peptide-binding specificities of the two pockets and determined the role of position beta69, using competition tests with the Ii-derived peptide CLIP and its mutated forms carrying all the aminoacidic substitutions in P4 and P6. Pocket 4 of HLA-DP2 showed high affinity for positively charged, aromatic, and polar residues, whereas aliphatic residues were disfavored. Pocket 4 of the DP2K69 variant showed a reduced aminoacid selectivity with aromatic residues most preferred. Pocket 6 of HLA-DP2 showed high affinity for aromatic residues, which was increased in DP2K69 and extended to arginine. Finally, we used the experimental data to determine the best molecular-modeling approach for assessing aminoacid selectivity of the two pockets. The results with best predictive value were obtained when single aminoacids were evaluated inside each single pocket, thus, reducing the influence of the overall peptide/ major histocompatibility complex interaction. In conclusion, the HLA-DPbeta69 polymorphism plays a fundamental role in the peptide-binding selectivity of HLA-DP. Furthermore, as this polymorphism is the main change in the pocket 4 area of HLA-DP, it could represent a supertype among HLA-DP molecules significantly contributing to the selection of epitopes presented in the context of this HLA isotype. C1 Univ Roma Tor Vergata, Dipartimento Med Interna, I-00133 Rome, Italy. L Spallanzani IRCCS, INMI, Div Resp Dis, Rome, Italy. CNR, Inst Cell Biol, Rome, Italy. Univ Complutense, Dept Microbiol 2, E-28040 Madrid, Spain. Univ Roma Tor Vergata, Dept Biol, Lab Immunochem & Mol Pathol, I-00133 Rome, Italy. Intercell, Vienna, Austria. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Amicosante, M (reprint author), Univ Roma Tor Vergata, Dipartimento Med Interna, Via Montpellier 1, I-00133 Rome, Italy. RI Fraziano, Maurizio/F-1425-2013; Arroyo, Javier/E-9308-2016 OI Fraziano, Maurizio/0000-0002-5643-0769; Arroyo, Javier/0000-0002-1971-1721 NR 59 TC 32 Z9 32 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD DEC PY 2003 VL 62 IS 6 BP 459 EP 471 DI 10.1046/j.1399-0039.2003.00131.x PG 13 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 742DG UT WOS:000186500300002 PM 14617029 ER PT J AU Lee, HM Cusick, RA Utsunomiya, H Ma, PX Langer, R Vacanti, JP AF Lee, HM Cusick, RA Utsunomiya, H Ma, PX Langer, R Vacanti, JP TI Effect of implantation site on hepatocytes heterotopically transplanted on biodegradable polymer scaffolds SO TISSUE ENGINEERING LA English DT Article ID LIVER; TISSUE; FAILURE; MODEL AB We investigated the engraftment of heterotopically transplanted hepatocytes in three sites: the subcutaneous space, the small intestinal mesentery, and the omentum to determine the optimal location for tissue-engineered liver constructs. Hepatocytes were isolated from inbred Lewis rats and placed on polymer constructs. Cell-polymer constructs were implanted into the subcutaneous space of the abdominal wall, the small intestinal mesentery, and the omentum of Lewis rats. One group of rats had undergone previous portacaval shunt. Animals were killed 2 or 4 weeks after implantation and the constructs were analyzed for engraftment, using computer-assisted morphometric analysis. Engraftment was greatest in the omentum with less engraftment in the mesentery. There was minimal engraftment in the subcutaneous space in all specimens. Prior portacaval shunt increased engraftment in the mesentery and the omentum, but not the subcutaneous space. The omentum is the most favorable bed for engraftment of hepatocyte-polymer tissue-engineered constructs and the addition of a portacaval shunt increases survival of transplanted hepatocytes in the omentum and mesentery. C1 Univ Calif San Francisco, Med Ctr, Dept Surg, Fetal Treatment Ctr, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Childrens Hosp, Lab Transplantat & Tissue Engn, Boston, MA 02115 USA. RP Lee, HM (reprint author), Univ Calif San Francisco, Med Ctr, Dept Surg, Fetal Treatment Ctr, 513 Parnassus,Suite HSW 1601, San Francisco, CA 94143 USA. NR 18 TC 32 Z9 34 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 2003 VL 9 IS 6 BP 1227 EP 1232 DI 10.1089/10763270360728134 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA 748YP UT WOS:000186889200016 PM 14670110 ER PT J AU Gardner-Thorpe, J Grikscheit, TC Ito, H Perez, A Ashley, SW Vacanti, JP Whang, EE AF Gardner-Thorpe, J Grikscheit, TC Ito, H Perez, A Ashley, SW Vacanti, JP Whang, EE TI Angiogenesis in tissue-engineered small intestine SO TISSUE ENGINEERING LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIAL ORGANOID UNITS; FETAL-RAT INTESTINE; NATIVE SMALL-BOWEL; PARENTERAL-NUTRITION; SUSTAINED-RELEASE; IN-VIVO; TRANSPLANTATION; SCAFFOLDS; ANASTOMOSIS AB Tissue-engineered intestine offers promise as a potential novel therapy for short bowel syndrome. In this study we characterized the microvasculature and angiogenic growth factor profile of the engineered intestine. Twenty-three tissue-engineered small intestinal grafts were harvested from Lewis rat recipients 1 to 8 weeks after implantation. Architectural similarity to native bowel obtained from juvenile rats was assessed with hematoxylin and eosin-stained sections. Capillary density, measured after immunohistochemical staining for CD34, was expressed as number of capillaries per 1000 nuclei. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) tissue levels were measured by ELISA and normalized to total protein. Over the 8-week period cysts increased in volume (0.5 cm(3) at week 1 versus 12.6 cm(3) at week 8) and mass (1.30 +/- 0.29 versus 9.74 +/- 0.3 g; mean +/- SEM). Muscular and mucosal layers increased in thickness, but capillary density remained constant (82.95 +/- 4.81 capillaries per 1000 nuclei). The VEGF level was significantly higher in juvenile rat bowel than in engineered cyst (147.6 +/- 23.9 versus 42.3 +/- 3.4 pg/mg; p < 0.001). Tissue bFGF levels were also higher (315 +/- 65.48 versus 162.3 +/- 15.09 pg/mg; p < 0.05). The mechanism driving angiogenesis differs in engineered intestine and in normal bowel. VEGF and bFGF delivery may prove useful for bioengineering of intestine. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Whang, EE (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. NR 34 TC 25 Z9 26 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 2003 VL 9 IS 6 BP 1255 EP 1261 DI 10.1089/10763270360728161 PG 7 WC Cell & Tissue Engineering SC Cell Biology GA 748YP UT WOS:000186889200019 PM 14670113 ER PT J AU Fagan, P Stoddard, AM Hunt, MK Frazier, L Girod, K Sorensen, G AF Fagan, P Stoddard, AM Hunt, MK Frazier, L Girod, K Sorensen, G TI The feasibility of evaluating a tobacco control intervention for working youth SO TOBACCO CONTROL LA English DT Article ID SMOKING CESSATION; WORKPLACE SMOKING; CIGARETTE-SMOKING; ADOLESCENTS; HEALTH; CONSEQUENCES; ASSOCIATION AB Objectives: To describe the feasibility of implementing evaluation methods for a worksite tobacco control intervention for teens. Indicators of feasibility included employment stability, response rates to multiple surveys, and self reported 30 day smoking. Design: Grocery stores that were part of a single chain were randomised to four intervention stores and five control stores as part of the SMART project, a phase II methods development study designed to reduce smoking among working adolescents. Subjects: Data on smoking in the last 30 days and employment patterns were collected from working teens aged 15-18 years at seven data points over the 12 month intervention period using cross sectional surveys. Results: Data on employment stability indicate that employee turnover rates averaged 21% over the seven administrations. Response rates for the seven surveys ranged from 43-77% and were slightly greater in the control stores than the interventions stores (71% v 59%, p=0.06). Mean current smoking at the individual store level ranged from 9-32% and there was a negative correlation between smoking prevalence and response rate by survey and by store (-0.029, p=0.03). Among smokers who completed at least two surveys, there were no significant differences between intervention and control store on changes in the frequency of smoking. Conclusions: Evaluating a tobacco control intervention in the grocery store setting requires multiple survey assessments to monitor changes in smoking among adolescents. Strategies are needed to maintain high response rates and increase the number of multiple responses from eligible teens. C1 NCI, Div Canc Control & Populat Sci, Tobacco Control Res Branch, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Boston, MA 02125 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Frazier, L (reprint author), 6130 Execut Blvd,EPN 4042,MSC 7337, Bethesda, MD 20892 USA. NR 29 TC 4 Z9 4 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD DEC PY 2003 VL 12 SU 4 BP 34 EP 39 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 758LJ UT WOS:000187635600006 ER PT J AU Hunt, MK Fagan, P Lederman, R Stoddard, A Frazier, L Girod, K Sorensen, G AF Hunt, MK Fagan, P Lederman, R Stoddard, A Frazier, L Girod, K Sorensen, G TI Feasibility of implementing intervention methods in an adolescent worksite tobacco control study SO TOBACCO CONTROL LA English DT Article ID HEALTH PROMOTION PROGRAMS; SMOKING PREVENTION PROGRAMS; PEER EDUCATION; SOCIAL INFLUENCES; DRUG-ABUSE; PARTICIPATION; CRITIQUE; PROJECT; TRIAL AB Objective: To present feasibility data on SMART, the first teen worksite behavioural tobacco control intervention. Design: This phase II study was designed to estimate the efficacy and feasibility of a small scale, randomised, controlled intervention. Setting and subjects: This study, addressing youths aged 15-18 years, was implemented in four intervention and five control grocery stores that had an average of 44 eligible teens. Interventions: The tobacco use cessation and prevention interventions were based on social influences and peer leader models. Employee break rooms served as centres both for interactive activities including open houses, teen advisory boards, peer leader interviews, games and contests; and non-interactive interventions including bulletin boards and table tents with health messages and home mailings. Main process measures: Project staff collected process data on the extent of implementation of intervention activities, participation rates in activities, and contacts with peer leaders. On the final survey, teens reported on awareness of, participation in, and motivation for participating in project activities. Results: Indicators of feasibility were identified and discussed, including the number of activities implemented, teen participation, management support, cost, and barriers to and facilitators of implementation. During the 12 month intervention, a mean of 24.1 interactive activities and 55.3 non-interactive activities were implemented, and a mean 14.2% participation rate per activity per site was achieved. Eighty four per cent of teens reported being aware of SMART, and 39% reported participating in interactive and 67% in non-interactive activities. Conclusions: Teen smoking cessation rates in worksite programmes might be improved if they are conducted in companies where there is job stability and if teen programmes are part of worksite-wide tobacco control programmes that include both teens and adults. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. NCI, Tobacco Control Res Branch, Rockville, MD USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Hunt, MK (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,Room SM256, Boston, MA 02115 USA. NR 39 TC 11 Z9 11 U1 2 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD DEC PY 2003 VL 12 SU 4 BP 40 EP 45 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 758LJ UT WOS:000187635600007 ER PT J AU Fujii, S AF Fujii, S TI Evaluation of hypersensitivity to anthraquinone-related substances SO TOXICOLOGY LA English DT Article DE anthraquinone dyes; quinizarin; contact hypersensitivity; cross-sensitivity ID DELAYED CONTACT HYPERSENSITIVITY; PIG MAXIMIZATION TEST; GUINEA-PIG; ALLERGENS; IDENTIFICATION; DERMATITIS; ASSAY; DYES AB Evaluation of hypersensitivity to anthraquinone dyes, which are widely used as color additives, was performed in guinea pigs. In animals sensitized with 1% commercial-grade D&C Green No. 6 (Quinizarin Green SS, CI61565), subsequent challenge with the same dye showed a dose-dependent hypersensitivity reaction, whereas challenge with D&C Green No. 6 purified by recrystallization did not. Guinea pigs sensitized with commercial-grade D&C Green No. 6 showed a positive reaction to challenge with quinizarin, an intermediate in dye synthesis, but not to p-toluidine, another intermediate. It was confirmed that quinizarin itself induced hypersensitivity. The cross-reactivity of four kinds of purified dyes, in which the quinizarin contents were 1.2ppm or less, was evaluated. Purified D&C Green No. 5 (Alizarin Cyanin Green F, CI61570), D&C Green No. 6 and Ext. D&C Violet No. 2 (Alizurol Purple, CI60730) did not produce a hypersensitivity response, while D&C Violet No. 2 (Alizurin Purple SS, CI60725) did. We found that D&C Green No. 5, D&C Green No. 6 and Ext. D&C Violet No. 2 do not intrinsically induce hypersensitivity, and we conclude that the reaction to challenge with the commercial-grade dyes is due to quinizarin contaminating them. In contrast, D&C Violet No. 2 per se induced hypersensitivity. A structure-activity study indicated that 1-hydroxyl and 4-hydroxyl groups in the anthraquinone structure are key factors in hypersensitivity induction by anthraquinone-related compounds. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Fujii, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, E Bldg 149,13th St, Charlestown, MA 02129 USA. NR 28 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 1 PY 2003 VL 193 IS 3 BP 261 EP 267 DI 10.1016/S0300-483X(03)00270-1 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 745DP UT WOS:000186674100004 PM 14599762 ER PT J AU Joseph, JS Thirumangalathu, S Tsang, F Wong, FWS Kini, RM AF Joseph, JS Thirumangalathu, S Tsang, F Wong, FWS Kini, RM TI Trocarin, a blood coagulation factor Xa homologue from snake venom, causes inflammation and mitogenesis SO TOXICON LA English DT Article DE Group D prothrombin activator; EPR-1; Tropidechis carinatus; foot pad edema; mitogenesis; airway smooth muscle cells ID CELL PROTEASE RECEPTOR-1; SMOOTH-MUSCLE-CELLS; PROTHROMBIN ACTIVATORS; ENDOTHELIAL-CELLS; LIGAND-BINDING; IN-VIVO; EXPRESSION; GENE; IDENTIFICATION; HEMOSTASIS AB coagulation factor Xa (FXa). Both trocarin and FXa activate prothrombin to mature thrombin and have similar requirements for cofactors, such as factor Va, Ca2+ ions and phospholipids. In addition to its hemostatic functions, human FXa causes inflammation and induces mitogenesis in several cell types due to its interaction with effector protease receptor-1 (EPR-1). The inter-EGF domain region (L-83 FTXRL88) of FXa implicated in EPR-1-binding is distinctly different in trocarin (K(83)VLYQS(88)). Here we show that, interestingly, trocarin also causes edema in the mouse footpad; the inflammation, accompanied by a large purplish clot, is more persistent than the transient edema caused by FXa. Histological examination indicates significant differences between edema induced by FXa and trocarin. Moreover, trocarin-induced edema is not inhibited by a synthetic peptide based on the FXa-binding region of EPR-1 indicating that the inflammation is probably mediated by a mechanism independent of EPR-1-binding. Trocarin, like FXa, also has a mitogenic effect on bronchial smooth muscle cells mediated by an EPR-1-independent mechanism. Hence trocarin, being closely related to FXa, has similar non-hemostatic functions in mediating inflammation and mitogenesis, yet appears to act by distinctly different mechanisms. (C) 2003 Elsevier Ltd. All rights reserved. C1 Natl Univ Singapore, Fac Med, Dept Biochem, Singapore 117597, Singapore. Natl Univ Singapore, Fac Med, Singapore Dept Biochem, Singapore 117597, Singapore. Natl Univ Singapore, Fac Med, Singapore Dept Pharmacol, Singapore 117597, Singapore. Natl Univ Singapore, Fac Med, Singapore Dept Biol Sci, Singapore 117543, Singapore. Singapore Genome Inst Singapore, Singapore 119607, Singapore. Harvard Univ, Sch Med, Joslin Diabet Ctr, Singapore Dept Cell & Mol Physiol, Boston, MA 02215 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Biochem & Mol Biophys, Richmond, VA 23298 USA. RP Kini, RM (reprint author), Natl Univ Singapore, Fac Sci, Dept Biol Sci, 14 Sci Dr, Singapore 117543, Singapore. RI Kini, Manjunatha/H-8029-2012; Wong, W.S. Fred/D-8205-2013 NR 38 TC 9 Z9 9 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD DEC PY 2003 VL 42 IS 7 BP 769 EP 776 DI 10.1016/j.toxicon.2003.10.020 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 760PP UT WOS:000187843100010 PM 14757208 ER PT J AU Anderson, K AF Anderson, K TI Broadening the spectrum of patient groups at risk for transfusion-associated GVHD: implications for universal irradiation of cellular blood components SO TRANSFUSION LA English DT Editorial Material ID VERSUS-HOST DISEASE; HLA-HOMOZYGOUS DONORS; PREVENTION; DIAGNOSIS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, K (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 18 TC 15 Z9 16 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2003 VL 43 IS 12 BP 1652 EP 1654 DI 10.1111/j.0041-1132.2003.00631.x PG 3 WC Hematology SC Hematology GA 750TT UT WOS:000187014900002 PM 14641857 ER PT J AU Lawrence, VA Silverstein, JH Cornell, JE Pederson, T Noveck, H Carson, JL AF Lawrence, VA Silverstein, JH Cornell, JE Pederson, T Noveck, H Carson, JL TI Higher Hb level is associated with better early functional recovery after hip fracture repair SO TRANSFUSION LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; BLOOD-CELL TRANSFUSIONS; INTENSIVE-CARE UNIT; HEMODIALYSIS-PATIENTS; EXERCISE CAPACITY; PHYSICAL PERFORMANCE; ABDOMINAL-SURGERY; VASCULAR PATIENTS; HEMOGLOBIN; RISK AB BACKGROUND: The benefits and indications for blood transfusion are controversial. One possible reason to transfuse is to improve functional recovery after major surgery. However, the data linking improved function with higher Hb concentration are limited. STUDY DESIGN AND METHODS: A retrospective cohort study was performed in 5793 patients at least 60 years old undergoing hip fracture repair at 20 academic and community hospitals. The primary outcome was distance walked at the time of discharge from the hospital. The mean postoperative Hb concentration was the main exposure variable and was defined as the average value from Day 1 after surgery to discharge. We used robust regression to assess the association between postoperative Hb level with distance walked, controlling for other preoperative variables that could influence functional recovery. RESULTS: On bivariate analysis, the predicted distance walked at discharge in feet (95% CI) increased with higher Hb levels (7 g/dL, 56 feet [42-70]; 8 g/dL, 61 feet [54-68]; 9 g/dL, 67 feet [64-70]; 10 g/dL, 74 feet [72-77]; 11 g/dL, 83 feet [80-85]; 12 g/dL, 92 feet [87-96]). After adjustment for other factors associated with ability to walk, higher average postoperative Hb level was independently associated with walking greater distance (p < 0.001). CONCLUSIONS: Higher postoperative Hb level may improve functional recovery after hip fracture repair. If confirmed with clinical trials, this finding would provide a rationale to maintain higher Hb concentrations in elderly patients recovering from surgery. C1 STVHCS, ALMD, VERDICT, 11C6, San Antonio, TX USA. VERDICT, Vet Affairs Hlth Serv Res & Dev Ctr Excellence, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Gen Med, Dept Med, San Antonio, TX 78285 USA. NYU, Mt Sinai Sch Med, Dept Anesthesiol, New York, NY USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, Dept Med, New Brunswick, NJ USA. RP Lawrence, VA (reprint author), STVHCS, ALMD, VERDICT, 11C6, 7400 Merton Minter Blvd, San Antonio, TX USA. FU AHRQ HHS [1R01HS07322] NR 44 TC 91 Z9 108 U1 0 U2 4 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2003 VL 43 IS 12 BP 1717 EP 1722 DI 10.1046/j.0041-1132.2003.00581.x PG 6 WC Hematology SC Hematology GA 750TT UT WOS:000187014900014 PM 14641869 ER PT J AU Davis, AE AF Davis, AE TI The pathogenesis of hereditary angioedema SO TRANSFUSION AND APHERESIS SCIENCE LA English DT Article; Proceedings Paper CT International Meeting on Hereditary Angioedema CY OCT 24-27, 2003 CL TORONTO, CANADA ID MOLECULAR-WEIGHT KININOGEN; ANGIONEUROTIC EDEMA PLASMA; C1 INHIBITOR DYSFUNCTION; SERINE PROTEASES MASPS; EMBRYONIC STEM-CELLS; ENDOTHELIAL-CELLS; FACTOR-XII; BINDING-PROTEIN; VASCULAR-PERMEABILITY; FUNCTIONAL-ANALYSIS AB Hereditary angioedema (HAE), which is characterized by episodic localized angioedema of the skin or mucosa, results from heterozygous deficiency of the plasma protease inhibitor, Cl inhibitor (CIINH). The most obvious biologic role of CIINH, therefore, is prevention of excessive vascular permeability. A variety of data indicate that this role is primarily a product of regulation of the contact system proteases, factor XIIa and plasma kallikrein. The CIINH deficient mouse, although it does not have episodes of cutaneous angioedema, does have increased vascular permeability which is reversed by treatment with CIINH, with the plasma kallikrein inhibitor, DX88, and with the bradykinin 2 receptor (BUR) antagonist, Hoe140. In addition, mice deficient in both ClINH and the Bk2R do not have increased vascular permeability. These analyses strengthen the argument that angioedema is mediated by bradykinin. This mouse also provides a system to test new potential therapeutic approaches. In addition to its role in the regulation of vascular permeability, CIINH also is an important modulator of inflammatory responses via regulation of activation of both the contact and the complement systems, and very likely via activities unrelated to protease inhibition. (C) 2003 Elsevier Ltd. All rights reserved. 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. NR 60 TC 38 Z9 39 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1473-0502 J9 TRANSFUS APHER SCI JI Transfus. Apher. Sci. PD DEC PY 2003 VL 29 IS 3 BP 195 EP 203 DI 10.1016/j.transci.2003.08.012 PG 9 WC Hematology SC Hematology GA 738VC UT WOS:000186307700002 PM 14572810 ER PT J AU Binkley, KE Davis, AE AF Binkley, KE Davis, AE TI Estrogen-dependent inherited angioedema SO TRANSFUSION AND APHERESIS SCIENCE LA English DT Article; Proceedings Paper CT International Meeting on Hereditary Angioedema CY OCT 24-27, 2003 CL TORONTO, CANADA DE hereditary angioedema; estrogen ID HEREDITARY ANGIONEUROTIC EDEMA; CONVERTING-ENZYME-ACTIVITY; C1 ESTERASE INHIBITOR; FACTOR-XII; REPLACEMENT THERAPY; C1-ESTERASE INHIBITOR; POSTMENOPAUSAL WOMEN; ORAL-CONTRACEPTIVES; GENE-EXPRESSION; C1-INHIBITOR AB Classic forms of hereditary angioedema are characterized clinically by recurrent episodes of angioedema, biochemically by reduced C1 inhibitor level and/or function, and genetically by a heterogeneous group of mutations in the C1 inhibitor gene that have an autosomal dominant mode of transmission. Androgens and estrogens have significant clinical effects in patients with hereditary angioedema, and tend to have antagonist effects of the levels of Cl inhibitor protein. Androgens increase the levels of C1 inhibitor protein, reduce attacks of angioedema, and thus are an important therapy for patients. The mechanisms by which the sex steroid hormones achieve these effects are not understood. The recent recognition of a novel estrogen-dependent form of angioedema may offer important insights into the mechanisms by which the sex hormones exert their effects, and the pathogenesis and treatment of both estrogen-dependent and classic forms of hereditary angioedema. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Toronto, Dept Med, Div Clin Immunol & Allergy, Toronto, ON, Canada. Ctr Blood Res, Boston, MA 02115 USA. RP Binkley, KE (reprint author), 30 St Clair Ave W,201, Toronto, ON M4V 3A1, Canada. NR 32 TC 22 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1473-0502 J9 TRANSFUS APHER SCI JI Transfus. Apher. Sci. PD DEC PY 2003 VL 29 IS 3 BP 215 EP 219 DI 10.1016/j.transci.2003.08.002 PG 5 WC Hematology SC Hematology GA 738VC UT WOS:000186307700004 PM 14572812 ER PT J AU Bates, SH Myers, MG AF Bates, SH Myers, MG TI The role of leptin receptor signaling in feeding and neuroendocrine function SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID BODY-WEIGHT; ARCUATE NUCLEUS; FOOD-INTAKE; MELANOCORTIN RECEPTORS; INDUCED ANOREXIA; OBESITY SYNDROME; NEUROPEPTIDE-Y; MESSENGER-RNA; OB/OB MICE; LONG-FORM AB The adipose-derived hormone leptin regulates energy balance and neuroendocrine function, and resistance to its appetite-suppressing effects might underlie common forms of obesity. Understanding the intracellular signaling pathways and hypothalamic neural circuitry by which leptin controls satiety and body weight is central to our understanding of leptin resistance and the identification of potential therapeutic targets. Here, we review the mechanisms by which leptin activates intracellular signaling and the roles of two specific leptin-activated signals [phosphatidylinositol 3-kinase and signal transducer and activator of transcription-3 (STAT3)] in the regulation of body weight and neuroendocrine function. The pathway by which leptin activates STAT3 is particularly intriguing because it is crucial for the regulation of feeding but dispensable for the control of reproductive and growth axes. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Myers, MG (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 57768, DK56731] NR 56 TC 122 Z9 124 U1 0 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 2003 VL 14 IS 10 BP 447 EP 452 DI 10.1016/j.tem.2003.10.003 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 753GN UT WOS:000187223800004 PM 14643059 ER PT J AU Raftery, LA Sutherland, DJ AF Raftery, LA Sutherland, DJ TI Gradients and thresholds: BMP response gradients unveiled in Drosophila embryos SO TRENDS IN GENETICS LA English DT Review ID SHORT GASTRULATION GENE; DORSAL-VENTRAL PATTERN; MORPHOGEN GRADIENT; DEVELOPMENTAL BIOLOGY; SIGNAL-TRANSDUCTION; IMAGINAL DISCS; DPP; RECEPTOR; SMAD; AMNIOSEROSA AB Bone morphogenetic proteins (BMP) direct dorsal-ventral patterning in both invertebrate and vertebrate embryos, with strong evolutionary conservation of molecular components of the pathway. Dorsal-ventral patterning of the early Drosophila embryo is a powerful experimental system to probe mechanisms of BMP gradient formation and interpretation. Recent studies have found that spatial patterns of activated BMP signal transducers in Drosophila go through an unexpected transition: a shallow gradient of weak responses at mid-cellularization changes to a step gradient of stronger responses in cellularized embryos. The transition between two gradients of different shape yields new insights into the progression of Drosophila dorsal-ventral patterning and raises new issues about the mechanisms of gradient formation. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England. RP Raftery, LA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NIGMS NIH HHS [R01 GM060501] NR 64 TC 37 Z9 41 U1 2 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD DEC PY 2003 VL 19 IS 12 BP 701 EP 708 DI 10.1016/j.tig.2003.10.009 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 753GG UT WOS:000187223200010 PM 14642751 ER PT J AU LeGuern, C AF LeGuern, C TI Regulation of T-cell functions by MHC class II self-presentation SO TRENDS IN IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; RENAL-ALLOGRAFTS; DENDRITIC CELLS; MINIATURE SWINE; AUTOIMMUNE ENCEPHALOMYELITIS; RHEUMATOID-ARTHRITIS; BLOOD-TRANSFUSIONS; TRANSGENIC MICE; TOLERANCE; MOLECULES AB The role of MHC class II in the control of T-cell responses to self and foreign antigens is still unclear. No unifying principle yet explains how class II molecules repress immunity to self or allogeneic antigens. Our recent data in a model of tolerance to allogeneic grafts, probably induced by allele-specific class II peptides, suggest that it is by presenting themselves [class II peptide(s) docked on self class II, in a complex we have named T-Lo] that class II controls T-cell activity. The engagement of the regulatory T (T-reg)-cell T-cell receptor (TCR) with self T-Lo would explain the beneficial effect of donor-recipient class 11 matching in clinical transplantation, the correlation between T-cell suppression and class II, and the altered T-reg-cell functions observed in class II-dependent autoimmune pathologies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Biol Res Ctr, Boston, MA 02129 USA. RP LeGuern, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Biol Res Ctr, Bldg 149-9019, Boston, MA 02129 USA. FU NIAID NIH HHS [2R01AI33053] NR 55 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD DEC PY 2003 VL 24 IS 12 BP 633 EP 638 DI 10.1016/j.it.2003.10.010 PG 6 WC Immunology SC Immunology GA 756VL UT WOS:000187504500006 PM 14644136 ER PT J AU Hurley, BP McCormick, BA AF Hurley, BP McCormick, BA TI Translating tissue culture results into animal models: the case of Salmonella typhimurium SO TRENDS IN MICROBIOLOGY LA English DT Review ID ENTERICA SEROVAR TYPHIMURIUM; INTESTINAL EPITHELIAL-CELLS; SECRETED EFFECTOR PROTEINS; NUCLEAR RESPONSES; TYPHOID-FEVER; HOST-CELLS; BACTERIAL INTERNALIZATION; PROINFLAMMATORY RESPONSE; NEUTROPHIL MIGRATION; DENDRITIC CELLS AB Investigators use both in vitro and in vivo models to better understand infectious disease processes. Both models are extremely useful in research, but there exists a significant gap in complexity between the highly controlled reductionist in vitro systems and the largely undefined, but relevant variability encompassing in vivo animal models. In an effort to understand how Salmonella initiates disease at the intestinal epithelium, in vitro models have served a useful purpose in allowing investigators to identify molecular mechanisms responsible for Salmonella invasion of host cells and stimulation of host inflammatory responses. Identification of these molecular mechanisms has generated hypotheses that are now being tested using in vivo models. Translating the in vitro findings into the context of an animal model and subsequently to human disease remains a difficult challenge for any disease process. C1 Massachusetts Gen Hosp, Combined Program pediat Gastroenterol, Charlestown, MA 02129 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Combined Program pediat Gastroenterol, 114 16th St,114-3503, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK33506, DK56754] NR 62 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD DEC PY 2003 VL 11 IS 12 BP 562 EP 569 DI 10.1016/j.tim.2003.10.002 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 758HV UT WOS:000187629100004 PM 14659688 ER PT J AU Ji, RR Kohno, T Moore, KA Woolf, CJ AF Ji, RR Kohno, T Moore, KA Woolf, CJ TI Central sensitization and LTP: do pain and memory share similar mechanisms? SO TRENDS IN NEUROSCIENCES LA English DT Review ID DORSAL-HORN NEURONS; LONG-TERM POTENTIATION; RAT SPINAL-CORD; SPINOTHALAMIC TRACT NEURONS; CUTANEOUS MECHANORECEPTIVE FIELDS; AMPA RECEPTOR TRAFFICKING; ACTIVATED PROTEIN-KINASE; PRIMARY SENSORY NEURONS; ROOT GANGLION NEURONS; I PROJECTION NEURONS AB Synaptic plasticity is fundamental to many neurobiological functions, including memory and pain. Central sensitization refers to the increased synaptic efficacy established in somatosensory neurons in the dorsal horn of the spinal cord following intense peripheral noxious stimuli, tissue injury or nerve damage. This heightened synaptic transmission leads to a reduction in pain threshold, an amplification of pain responses and a spread of pain sensitivity to non-injured areas. In the cortex, LTP - a long-lasting highly localized increase in synaptic strength - is a synaptic substrate for memory and learning. Analysis of the molecular mechanisms underlying the generation and maintenance of central sensitization and LTP indicates that, although there are differences between the synaptic plasticity contributing to memory and pain, there are also striking similarities. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. RI yu, yan/C-2322-2012; OI Ji, Ru-Rong/0000-0002-9355-3688 NR 108 TC 719 Z9 771 U1 7 U2 47 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD DEC PY 2003 VL 26 IS 12 BP 696 EP 705 DI 10.1016/j.tins.2003.09.017 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 751QJ UT WOS:000187078200012 PM 14624855 ER PT J AU Kane, CJ Lubeck, DP Knight, SJ Spitalny, M Downs, TM Grossfeld, GD Pasta, DJ Mehta, SS Carroll, PR AF Kane, CJ Lubeck, DP Knight, SJ Spitalny, M Downs, TM Grossfeld, GD Pasta, DJ Mehta, SS Carroll, PR TI Impact of patient educational level on treatment for patients with prostate cancer: Data from CaPSURE SO UROLOGY LA English DT Article ID QUALITY-OF-LIFE; SOCIOECONOMIC-STATUS; RADICAL PROSTATECTOMY; DECISION-MAKING; MEN; AGE; THERAPY AB Objectives. To examine the effect of a patient's educational level on treatment selection for patients with newly diagnosed prostate cancer. A patient's educational level may impact a patient's understanding and perception of the risks and benefits of the treatment options for prostate cancer. Methods. We examined 3484 patients in CaPSURE with prostate cancer between 1992 and 2001. Chi-square and multinomial logistic regression analyses were performed to determine the role of education level in primary treatment received relative to other pretreatment predictors (age, race, insurance status, prostate cancer risk, comorbidity). Prostate cancer risk stratification was determined by serum prostate-specific antigen level and tumor stage and grade. Results. The mean patient age was 67.7 +/- 8.3 years, and the mean prostate-specific antigen level was 13.0 +/- 18.7 ng/mL. Of the 3484 patients, 16.7% had less than a high school education, 27.0% had completed high school or technical school, 19.5% had had some college, 18.0% had graduated from college, and 18.6% had had some graduate education. In bivariate analysis, the factors predictive of treatment selection were patient age, race, education, insurance status, risk group, and patient comorbidity (all P <0.001). In multinomial regression analysis, the factors predicting treatment received were age, race, cancer risk group, and comorbidity. For patients older than 75 years, those with a higher education level received more aggressive treatment (radiotherapy versus hormonal therapy) than did those with less education. Conclusions. Patient age, race, cancer risk group, comorbidity, and, for men older than 75 years, education level are the factors predictive of the primary treatment received by men with newly diagnosed prostate cancer. (C) 2003 Elsevier Inc. C1 Univ Calif San Francisco, Sch Med, Dept Urol, Program Urol Oncol,Urol Outcomes Res Grp, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Mt Zion Comprehens Canc Ctr, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Serv Urol, San Francisco, CA USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Kane, CJ (reprint author), Univ Calif San Francisco, Sch Med, Dept Urol, Program Urol Oncol,Urol Outcomes Res Grp, 1600 Divisadero St,Room A-607, San Francisco, CA 94143 USA. OI Pasta, David/0000-0003-2637-9293 NR 16 TC 26 Z9 26 U1 0 U2 1 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 DEC PY 2003 VL 62 IS 6 BP 1035 EP 1039 DI 10.1016/S0090-4295(03)00778-7 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 811RV UT WOS:000220789900013 PM 14665350 ER PT J AU D'Amico, AV Tempany, CM Schultz, D Cormack, RA Hurwitz, M Beard, C Albert, M Kooy, H Jolesz, F Richie, JP AF D'Amico, AV Tempany, CM Schultz, D Cormack, RA Hurwitz, M Beard, C Albert, M Kooy, H Jolesz, F Richie, JP TI Comparing PSA outcome after radical prostatectomy or magnetic resonance imaging-guided partial prostatic irradiation in select patients with clinically localized adenocarcinoma of the prostate SO UROLOGY LA English DT Article ID RADIATION-THERAPY; BRACHYTHERAPY; CANCER AB Objectives. To determine whether high-dose radiation delivered to a subvolume of the prostate gland (peripheral zone) using intraoperative magnetic resonance imaging-guided brachytherapy provided comparable 5-year prostate-specific antigen (PSA) control rates to radical prostatectomy (RP) in select patients compared prospectively but in a nonrandomized setting. Methods. Between 1997 and 2002, 322 and 196 patients with clinical Stage T1c, PSA less than 10 ng/mL, biopsy Gleason score 3 + 4 or less, and without perineural invasion underwent RP or intraoperative magnetic resonance imaging-guided brachytherapy, respectively, and had a 2-year minimal follow-up. Cox regression multivariable analysis was used to evaluate whether the initial therapy, pretreatment PSA level, biopsy Gleason score, percentage of positive biopsies, or prostate gland volume were predictors of the time to post-therapy PSA failure. PSA failure was estimated using the Kaplan-Meier method and defined using the American Society for Therapeutic Radiology Oncology consensus definition. Results. Only the percentage of positive prostate biopsies (P-Cox = 0.02) was a significant predictor of the time to post-treatment PSA failure. However, the distribution of this parameter between RP and brachytherapy-treated patients was not significantly different (Pchi-square = 0.25). The initial therapy did not predict for the time to post-therapy PSA failure (P-Cox = 0.18). The 5-year estimate of PSA control was 93% versus 95% (Plog-rank = 0.16) for the RP and brachytherapy patients, respectively. Conclusions. Despite only partial prostatic irradiation using intraoperative magnetic resonance imaging-guided brachytherapy, similar 5-year estimates of PSA control were found for both brachytherapy and RP-managed patients. (C) 2003 Elsevier Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,Lower Level 2, Boston, MA 02115 USA. OI Cormack, Robert/0000-0001-5553-9984 FU NCI NIH HHS [R25 CA089017]; NIA NIH HHS [R01: AG 19513-01] NR 22 TC 31 Z9 31 U1 0 U2 2 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 DEC PY 2003 VL 62 IS 6 BP 1063 EP 1067 DI 10.1016/S0090-4295(03)00772-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 811RV UT WOS:000220789900019 PM 14665356 ER PT J AU Zhu, HQ Wang, Y Hu, RL Ren, B Zhou, Q Jiang, ZK Gui, SY AF Zhu, HQ Wang, Y Hu, RL Ren, B Zhou, Q Jiang, ZK Gui, SY TI Distribution and expression of non-muscle myosin light chain kinase in rabbit livers SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SECRETORY CASCADE; PROTEIN-KINASE; PHOSPHORYLATION; LOCALIZATION; CELL; ORGANIZATION; CONTRACTION; ACTIVATION; ENTRY; RAT AB AIM: To study the distribution and expression of non-muscle myosin light chain kinase (nmMLCK) in rabbit livers. METHODS: Human nmMLCK N-terminal cDNA was amplified by polymerase chain reaction (PCR) and was inserted into pBKcmv to construct expression vectors. The recombinant plasmid was transformed into XL1-blue. Expression protein was induced by IPTG and then purified by SDS-PAGE and electroelution, which was used to prepare the polycolonal antibody to detect the distribution and expression of nmMLCK in rabbit livers with immunofluorescene techniques. RESULTS: The polyclonal antibody was prepared, by which nmMLCK expression was detected and distributed mainly in peripheral hepatocytes. CONCLUSION: nmMLCK can express in hepatocytes peripherally, and may play certain roles in the regulation of hepatic functions. C1 Anhui Med Univ, Mol Biol Lab, Hefei 230032, Anhui, Peoples R China. Anhui Med Univ, Dept Biochem, Hefei 230032, Anhui, Peoples R China. Anhui Prov Key Lab Genom Res, Hefei 230032, Anhui, Peoples R China. BIDMC, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Anhui Med Univ, Affiliated Hosp 1, Dept Resp Dis, Hefei 230032, Anhui, Peoples R China. PLA, Hosp 105, Hefei 230031, Anhui, Peoples R China. RP Wang, Y (reprint author), Anhui Med Univ, Mol Biol Lab, Hefei 230032, Anhui, Peoples R China. NR 27 TC 2 Z9 3 U1 0 U2 2 PU W J G PRESS PI BEIJING PA PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD DEC PY 2003 VL 9 IS 12 BP 2715 EP 2719 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 757YY UT WOS:000187606800018 PM 14669320 ER PT J AU Lacerda, ALT Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC AF Lacerda, ALT Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC TI Anatomical MRI study of basal ganglia in major depressive disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE neuroimaging; caudate; putamen; globus pallidus; mood disorders; unipolar depression; magnetic resonance imaging ID MAGNETIC-RESONANCE SPECTROSCOPY; PHOTON-EMISSION TOMOGRAPHY; MOOD DISORDERS; UNIPOLAR DEPRESSION; NEUROPSYCHIATRIC DISORDERS; PARKINSONS-DISEASE; BIPOLAR DISORDER; METABOLIC RATES; VOLUME; BRAIN AB The basal ganglia form a part of the brain neuroanatomic circuits that may be involved in mood regulation. Decreases in basal ganglia volumes have been previously reported in major depressive disorder patients in comparison to healthy controls. In this study, we measured caudate, putamen, and globus pallidus volumes in 25 patients with major depressive disorder (4 M; age +/- S.D. = 41 +/- 11 years) and 48 healthy controls (29 M; age +/- S.D. = 35 +/- 10 years), using high-resolution magnetic resonance imaging (MRI), in an attempt to replicate prior findings. Unlike most previous studies, we did not find significant differences between patient and control groups in basal ganglia volumetric measures. Nonetheless, there was a significant interaction between diagnosis and cerebral hemisphere, with MDD patients showing decreased asymmetry in globus pallidus volumes in comparison with healthy controls. Furthermore, in the patient group, left putamen volumes correlated inversely with length of illness, and left globus pallidus volume correlated directly with number of prior depressive episodes. These findings suggest that abnormalities in lateralization and possibly neurodegenerative changes in basal ganglia structures participate in the pathophysiology of major depressive disorder. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. State Univ Campinas, Sch Med Sci, Dept Med Psychol & Psychiat, Campinas, SP, Brazil. Univ Pavia, Sch Med, Dept Psychiat, Pavia, Italy. Univ Pittsburgh, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat MC7792, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Lacerda, Acioly/A-7052-2010; brambilla, paolo/B-4184-2010 OI Lacerda, Acioly/0000-0002-9370-0449; brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 30915, MH 01736] NR 59 TC 59 Z9 61 U1 5 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 30 PY 2003 VL 124 IS 3 BP 129 EP 140 DI 10.1016/S0925-4927(03)00123-9 PG 12 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 745VU UT WOS:000186711900001 PM 14623065 ER PT J AU Xu, RH AF Xu, RH TI Measuring explained variation in linear mixed effects models SO STATISTICS IN MEDICINE LA English DT Article DE empirical Bayes; explained randomness; Kullback-Leibler information; predicted random effects; residual sum of squares ID GOODNESS-OF-FIT; MAXIMUM-LIKELIHOOD; ASYMPTOTIC PROPERTIES; LONGITUDINAL DATA; VARIANCE; DEPENDENCE; TRIAL; BLUP AB We generalize the well-known R-2 measure for linear regression to linear mixed effects models. Our work was motivated by a cluster-randomized study conducted by the Eastern Cooperative Oncology Group, to compare two different versions of informed consent document. We quantify the variation in the response that is explained by the covariates under the linear mixed model, and study three types of measures to estimate such quantities. The first type of measures make direct use of the estimated variances; the second type of measures use residual sums of squares in analogy to the linear regression; the third type of measures are based on the Kullback-Leibler information gain. All the measures can be easily obtained from software programs that fit linear mixed models. We study the performance of the measures through Monte Carlo simulations, and illustrate the usefulness of the measures on data sets. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Xu, RH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 32 TC 181 Z9 182 U1 4 U2 41 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 30 PY 2003 VL 22 IS 22 BP 3527 EP 3541 DI 10.1002/sim.1572 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 739LD UT WOS:000186346600007 PM 14601017 ER PT J AU Wu, H Park, HY AF Wu, H Park, HY TI Protein kinase C-beta-mediated complex formation between tyrosinase and TRP-1 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE tyrosinase; TRP-1; PKC-beta; protein-protein interaction; pigmentation ID CONFORMATIONAL-CHANGES; INSULIN-RECEPTOR; OXIDASE ACTIVITY; DHICA OXIDASE; PIGMENTATION; MUTATION; GENE; MELANOGENESIS; MURINE; BROWN AB Tyrosinase, the key enzyme in melanogenesis, is activated when protein kinase C-beta (PKC-beta) phosphorylates the serine residues at amino acid positions 505 and 509. To further elucidate the mechanism by which phosphorylation of tyrosinase by PKC-beta leads to the activation of tyrosinase, a possible complex formation between phosphorylated tyrosinase and tyrosinase related protein-1 (TRP-1), a melanogenic protein suggested to influence tyrosinase activity, was investigated. Non-denaturing gel electrophoresis of melanocyte lysate revealed two molecular weight forms of TRP-1 and a monoclonal antibody against TRP-1 co-immunoprecipitated tyrosinase and TRP-1, suggesting that TRP-1 may be complexed with tyrosinase. Activation of PKC by treating melanocytes with phorbol 12,13-dibutyraie (PDBu) increased the level of tyrosinase co-immunoprecipitated with TRP-1; whereas a selective PKC inhibitor bisindolylmaleimide inhibited PDBu-induced increase in the level of tyrosinase co-immunoprecipitated with TRP-1. These results suggest that phosphorylation of tyrosinase by PKC-beta induces a complex formation between tyrosinase and TRP-1. (C) 2003 Elsevier Inc. All rights reserved. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Park, HY (reprint author), Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. FU NCI NIH HHS [CA R0172763] NR 37 TC 21 Z9 22 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 28 PY 2003 VL 311 IS 4 BP 948 EP 953 DI 10.1016/j.bbrc.2003.10.092 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 747KP UT WOS:000186803900023 PM 14623273 ER PT J AU Feske, S Okamura, H Hogan, PG Rao, A AF Feske, S Okamura, H Hogan, PG Rao, A TI Ca2+/calcineurin signalling in cells of the immune system SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACTIVATED T-CELLS; NF-KAPPA-B; CELLULAR PHOSPHATASE CALCINEURIN; TRANSCRIPTION FACTOR NFAT1; BETA-DEFICIENT MICE; NUCLEAR FACTOR; GENE-EXPRESSION; CYCLOSPORINE-A; IMMUNOSUPPRESSIVE AGENTS; PROTEIN PHOSPHATASE-1 AB Calcineurin is a serine-threonine - phosphatase that is expressed in a wide variety of tissues and has particularly critical functions in neurons, cardiac and skeletal muscle cells, and lymphocytes. This review focuses on recent studies elucidating the role of Ca2+/calcineurin signalling of the immune system. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA 72320]; NIAID NIH HHS [AI40127, AI54933] NR 92 TC 104 Z9 110 U1 3 U2 8 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 NOV 28 PY 2003 VL 311 IS 4 BP 1117 EP 1132 DI 10.1016/j.bbrc.2003.09.174 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 747KP UT WOS:000186803900048 PM 14623298 ER PT J AU Lleo, A Berezovska, O Ramdya, P Fukumoto, H Raju, S Shah, T Hyman, BT AF Lleo, A Berezovska, O Ramdya, P Fukumoto, H Raju, S Shah, T Hyman, BT TI Notch1 competes with the amyloid precursor protein for gamma-secretase and down-regulates presenilin-1 gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRIMARY MAMMALIAN NEURONS; INTRACELLULAR DOMAIN; TERMINAL FRAGMENT; PS1 DEFICIENCY; CELLS; FE65; APP; TRANSLOCATION; PROTEOLYSIS; INHIBITOR AB Presenilin 1 (PS1) is a critical component of the gamma-secretase complex, which is involved in the cleavage of several substrates including the amyloid precursor protein (APP) and Notch1. Based on the fact that APP and Notch are processed by the same gamma-secretase, we postulated that APP and Notch compete for the enzyme activity. In this report, we examined the interactions between APP, Notch, and PS1 using the direct gamma-secretase substrates, Notch 1 Deltaextracellular domain (N1DeltaEC) and APP carboxyl-terminal fragment of 99 amino acids, and measured the effects on amyloid-beta protein production and Notch signaling, respectively. Additionally, we tested the hypothesis that downstream effects on PS1 expression may coexist with the competition phenomenon. We observed significant competition between Notch and APP for gamma-secretase activity; transfection with either of two direct substrates of gamma-secretase led to a reduction in the gamma-cleaved products, Notch intracellular domain or amyloid-beta protein. In addition, however, we found that activation of the Notch signaling pathway, by either N1DeltaEC or Notch intracellular domain, induced down-regulation of PS1 gene expression. This finding suggests that Notch activation directly engages gamma-secretase and subsequently leads to diminished PS1 expression, suggesting a complex set of feedback interactions following Notch activation. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02114 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, Rm 2009,114-16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG15379] NR 33 TC 39 Z9 41 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 NOV 28 PY 2003 VL 278 IS 48 BP 47370 EP 47375 DI 10.1074/jbc.M308480200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400005 PM 12960155 ER PT J AU Forrest, JC Campbell, JA Schelling, P Stehle, T Dermody, TS AF Forrest, JC Campbell, JA Schelling, P Stehle, T Dermody, TS TI Structure-function analysis of reovirus binding to junctional adhesion molecule 1 - Implications for the mechanism of reovirus attachment SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CRYSTAL-STRUCTURE; ADENOVIRUS RECEPTOR; CELLULAR RECEPTOR; PROTEIN SIGMA-1; COXSACKIEVIRUS; FIBER; RESOLUTION; ANTIBODY; TYPE-3 AB Mammalian reoviruses are nonenveloped viruses with a long, filamentous attachment protein that dictates disease phenotypes following infection of newborn mice and is a structural homologue of the adenovirus attachment protein. Reoviruses use junctional adhesion molecule 1 (JAM1) as a serotype-independent cellular receptor. JAM1 is a broadly expressed immunoglobulin superfamily protein that forms stable homodimers and regulates tight-junction permeability and lymphocyte trafficking. We employed a series of structure-guided binding and infection experiments to define residues in human JAM1 (hJAM1) important for reovirus-receptor interactions and to gain insight into mechanisms of reovirus attachment. Binding and infection experiments using chimeric and domain deletion mutant receptor molecules indicate that the amino-terminal D1 domain of hJAM1 is required for reovirus attachment, infection, and replication. Reovirus binding to hJAM1 occurs more rapidly than homotypic hJAM1 association and is competed by excess hJAM1 in vitro and on cells. Crosslinking hJAM1 diminishes the capacity of reovirus to bind hJAM1 in vitro and on cells and negates the competitive effects of soluble hJAM1 on reovirus attachment. Finally, mutagenesis studies demonstrate that residues intimately associated with the hJAM1 dimer interface are critical for reovirus interactions with hJAM1. These results suggest that reovirus attachment disrupts hJAM1 dimers and highlight similarities between the attachment strategies of reovirus and adenovirus. C1 Vanderbilt Univ, Elizabeth B Lamb Ctr Pediat Res, Sch Med, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Microbiol & Immunol, Sch Med, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Pediat, Sch Med, Nashville, TN 37232 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. RP Dermody, TS (reprint author), Vanderbilt Univ, Elizabeth B Lamb Ctr Pediat Res, Sch Med, D7235 MCN, Nashville, TN 37232 USA. FU NCI NIH HHS [T32 CA09385, CA68485]; NIAID NIH HHS [R01 AI38296]; NIDDK NIH HHS [DK20593]; NIGMS NIH HHS [R01 GM67853] NR 47 TC 46 Z9 47 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 NOV 28 PY 2003 VL 278 IS 48 BP 48434 EP 48444 DI 10.1074/jbc.M305649200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400129 PM 12966102 ER PT J AU Ueki, K Fruman, DA Yballe, CM Fasshauer, M Klein, J Asano, T Cantley, LC Kahn, CR AF Ueki, K Fruman, DA Yballe, CM Fasshauer, M Klein, J Asano, T Cantley, LC Kahn, CR TI Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; INDUCED GLUCOSE-TRANSPORT; PHOSPHATIDYLINOSITOL 3-KINASE; RECEPTOR SUBSTRATE-1; GLYCOGEN-SYNTHASE; MICE LACKING; 3T3-L1 ADIPOCYTES; BROWN ADIPOCYTES; GLUT4 TRANSLOCATION; SKELETAL-MUSCLE AB Class IA phosphoinositide (PI) 3-kinase is composed of a p110 catalytic subunit and a p85 regulatory subunit and plays a pivotal role in insulin signaling. To explore the physiological roles of two major regulatory isoforms, p85alpha and p85beta, we have established brown adipose cell lines with disruption of the Pik3r1 or Pik3r2 gene. Pik3r1(-/-) (p85alpha(-/-)) cells show a 70% reduction of p85 protein and a parallel reduction of p110. These cells have a 50% decrease in PI 3-kinase activity and a 30% decrease in Akt activity, leading to decreased insulin-induced glucose uptake and anti-apoptosis. Pik3r2(-/-) (p85alpha(-/-)) cells show a 25% reduction of p85 protein but normal levels of p85-p110 and PI 3-kinase activity, supporting the fact that p85 is more abundant than p110 in wild type. p85beta(-/-) cells, however, exhibit significantly increased insulin-induced Akt activation, leading to increased anti-apoptosis. Reconstitution experiments suggest that the discrepancy between PI 3-kinase activity and Akt activity is at least in part due to the p85-dependent negative regulation of downstream signaling of PI 3-kinase. Indeed, both p85alpha(-/-) cells and p85beta(-/-) cells exhibit significantly increased insulin-induced glycogen synthase activation. p85alpha(-/-) cells show decreased insulin-stimulated Jun N-terminal kinase activity, which is restored by expression of p85alpha, p85beta, or a p85 mutant that does not bind to p110, indicating the existence of p85-dependent, but PI 3-kinase-independent, signaling pathway. Furthermore, a reduction of p85beta specifically increases insulin receptor substrate-2 phosphorylation. Thus, p85alpha and p85beta modulate PI 3-kinase-dependent signaling by multiple mechanisms and transmit signals independent of PI 3-kinase activation. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Univ Tokyo, Dept Internal Med, Grad Sch med, Tokyo 1130033, Japan. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [DK33201, DK34834, DK55545]; NIGMS NIH HHS [GM41890, R01 GM041890] NR 55 TC 146 Z9 153 U1 0 U2 10 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 NOV 28 PY 2003 VL 278 IS 48 BP 48453 EP 48466 DI 10.1074/jbc.M305602200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400131 PM 14504291 ER PT J AU Li, WH Moore, MJ Vasilieva, N Sui, JH Wong, SK Berne, MA Somasundaran, M Sullivan, JL Luzuriaga, K Greenough, TC Choe, H Farzan, M AF Li, WH Moore, MJ Vasilieva, N Sui, JH Wong, SK Berne, MA Somasundaran, M Sullivan, JL Luzuriaga, K Greenough, TC Choe, H Farzan, M TI Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus SO NATURE LA English DT Article ID ACUTE RESPIRATORY SYNDROME; MESSENGER-RNA EXPRESSION; AMINOPEPTIDASE-N; CARBOXYPEPTIDASE; VIRUS; SITE; LOCALIZATION; INHIBITORS; INFECTION; CLONING AB Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells(1,2). Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2)(3,4), isolated from SARS coronavirus (SARS-CoV)permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV. C1 Harvard Univ, Sch Med, Childrens Hosp, Perlmutter Lab,Pulm Div,Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Dept Med Microbiol & Mol Genet, Brigham & Womens Hosp, Partners AIDS Res Ctr,Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, Tufts Univ Core Facil, Boston, MA 02111 USA. Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. RP Choe, H (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Perlmutter Lab,Pulm Div,Dept Pediat, Boston, MA 02115 USA. OI Li, Wenhui/0000-0003-1305-7404; SUI, JIANHUA/0000-0002-1272-9662 NR 30 TC 878 Z9 1000 U1 2 U2 57 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 27 PY 2003 VL 426 IS 6965 BP 450 EP 454 DI 10.1038/nature02145 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747JE UT WOS:000186800800040 PM 14647384 ER PT J AU Kelsey, PB Chen, S Lauwers, GY McCluskey, RT Bazari, H Chan, A Pratt, J AF Kelsey, PB Chen, S Lauwers, GY McCluskey, RT Bazari, H Chan, A Pratt, J TI Case 37-2003: A 79-year-old man with coronary artery disease, peripheral vascular disease, end-stage renal disease, and abdominal pain and distention - Colonic necrosis with perforation due to sodium polystyrene sulfonate in sorbitol. Ischemic colitis, healed SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DIALYSIS-RELATED AMYLOIDOSIS; GASTROINTESTINAL-TRACT; KAYEXALATE-SORBITOL; INTESTINAL NECROSIS; SMALL-BOWEL; ENEMAS; EMBOLIZATION; INVOLVEMENT; INFARCTION C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kelsey, PB (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 22 TC 11 Z9 12 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 NOV 27 PY 2003 VL 349 IS 22 BP 2147 EP 2155 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 746ZV UT WOS:000186779700011 PM 14645643 ER PT J AU Hideshima, T Hayashi, T Chauhan, D Akiyama, M Richardson, P Anderson, K AF Hideshima, T Hayashi, T Chauhan, D Akiyama, M Richardson, P Anderson, K TI Biologic sequelae of c-Jun NH2-terminal kinase (JNK) activation in multiple myeloma cell lines SO ONCOGENE LA English DT Article DE multiple myeloma; JNK; growth arrest; p21; NF-kappa B ID N-TERMINAL KINASE; PROTEASOME INHIBITOR PS-341; MARROW STROMAL CELLS; KAPPA-B; THERAPEUTIC APPLICATIONS; MOLECULAR-MECHANISMS; INDUCED APOPTOSIS; DRUG-RESISTANCE; PLASMA-CELLS; INTERLEUKIN-6 AB Although c-Jun NH2-terminal kinase (JNK) is activated by treatment with therapeutic agents, the biologic sequelae of inhibiting constitutive activation of JNK has not yet been clarified. In this study, we examine the biologic effect of JNK inhibition in multiple myeloma (MM) cell lines. JNK-specific inhibitor SP600125 induces growth inhibition via induction of G1 or G2/M arrest in U266 and MM.1S multiple myeloma cell lines, respectively. Neither exogenous IL-6 nor insulin-like growth factor-1 (IGF-1) overcome SP600125-induced growth inhibition, and IL-6 enhances SP600125-induced G2/M phase in MM.1S cells. Induction of growth arrest is mediated by upregulation of p27(Kip1), without alteration of p53 and JNK protein expression. Importantly, SP600125 inhibits growth of MM cells adherent to bone marrow stromal cells (BMSCs). SP600125 induces NF-kappaB activation in a dose-dependent fashion, associated with phosphorylation of IkappaB kinase alpha (IKKalpha) and degradation of IkappaBalpha. In contrast, SP600125 does not affect phosphorylation of STAT3, Akt, and/or ERK. IKK-specific inhibitor PS-1145 inhibits SP600125-induced NF-kappaB activation and blocks the protective effect of SP600125 against apoptosis. Our data therefore demonstrate for the first time that inhibiting JNK activity induces growth arrest and activates NF-kappaB in MM cells. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P0-1 CA78378, R0-1 CA50947] NR 29 TC 55 Z9 56 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 27 PY 2003 VL 22 IS 54 BP 8797 EP 8801 DI 10.1038/sj.onc.1206919 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 748CP UT WOS:000186844900017 PM 14647474 ER PT J AU Go, AS Hylek, EM Chang, YC Phillips, KA Henault, LE Capra, AM Jensvold, NG Selby, JV Singer, DE AF Go, AS Hylek, EM Chang, YC Phillips, KA Henault, LE Capra, AM Jensvold, NG Selby, JV Singer, DE TI Anticoagulation therapy for stroke prevention in atrial fibrillation - How well do randomized trials translate into clinical practice? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RISK-FACTORS; ANTITHROMBOTIC THERAPY; ORAL ANTICOAGULATION; PREDICTING STROKE; RHYTHM CONTROL; DOSE WARFARIN; INTENSITY; EFFICACY; ASPIRIN; VALIDATION AB Context Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in randomized trials, but its effectiveness and safety in clinical practice is less clear. Objective To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death in atrial fibrillation within a usual care setting. Design Cohort study assembled between July 1, 1996, and December 31,1997, and followed up through August 31, 1999. Setting Large integrated health care system in Northern California. Patients Of 13559 adults with nonvalvular atrial fibrillation, 11526 were studied, 43% of whom were women, mean age 71 years, with no known contraindications to anticoagulation at baseline. Main Outcomes Ischemic stroke, peripheral embolism, hemorrhage, and death according to warfarin use and comorbidity status, as determined by automated databases, review of medical records, and state mortality files. Results Among 11526 patients, 397 incident thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred during 25341 person-years of follow-up, and warfarin therapy was associated with a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin. Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke. A nested case-control analysis estimated a 64% reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality. (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon, but the rate was moderately higher among those taking vs those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P=.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage. The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications (total cohort of 13559). Conclusions Warfarin is very effective for preventing ischemic stroke inpatients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small. Results of randomized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation. C1 Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway St,3rd Floor, Oakland, CA 94612 USA. FU NIA NIH HHS [AG15478] NR 49 TC 427 Z9 450 U1 0 U2 7 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 NOV 26 PY 2003 VL 290 IS 20 BP 2685 EP 2692 DI 10.1001/jama.290.20.2685 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 747CR UT WOS:000186788100020 PM 14645310 ER PT J AU Rosenheck, R Perlick, D Bingham, S Liu-Mares, W Collins, J Warren, S Leslie, D Allan, E Campbell, EC Caroff, S Corwin, J Davis, L Douyon, R Dunn, L Evans, D Frecska, E Grabowski, J Graeber, D Herz, L Kwon, K Lawson, W Mena, F Sheikh, J Smelson, D Smith-Gamble, V AF Rosenheck, R Perlick, D Bingham, S Liu-Mares, W Collins, J Warren, S Leslie, D Allan, E Campbell, EC Caroff, S Corwin, J Davis, L Douyon, R Dunn, L Evans, D Frecska, E Grabowski, J Graeber, D Herz, L Kwon, K Lawson, W Mena, F Sheikh, J Smelson, D Smith-Gamble, V CA Dept Vet Affairs Cooperative Study TI Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-LIFE; ATYPICAL ANTIPSYCHOTICS; REFRACTORY SCHIZOPHRENIA; CLINICAL-TRIAL; RATING-SCALE; CLOZAPINE; OUTCOMES; CARE; IMPROVEMENT; MEDICATION AB Context Although olanzapine has been widely adopted as a treatment of choice for schizophrenia, its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a standard antipsychotic drug. Objective To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia. Design and Setting Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers. Participants Three hundred nine patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder, serious symptoms, and serious dysfunction for the previous 2 years. Fifty-nine percent fully completed and 36% partially completed follow-up assessments. Interventions Patients were randomly assigned to receive flexibly dosed olanzapine, 5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n=159); or haloperidol, 5 to 20 mg/d (n=150), for 12 months. Main Outcome Measures 'Standardized measures of symptoms, quality of life, neurocognitive status, and adverse effects of medication. Veterans Affairs administrative data and interviews concerning non-VA service use were used to estimate costs from the perspective of the VA health care system and society as a whole (ie, consumption of all resources on behalf of these patients). Results There were no significant differences between groups in study retention; positive, negative, or total symptoms of schizophrenia; quality of life; or extrapyramidal symptoms. Olanzapine was associated with reduced akathisia in the intention-to-treat analysis (P<.001) and with lower symptoms of tardive dyskinesia in a secondary analysis including only observations during blinded treatment with study drug. Small but significant advantages were also observed on measures of memory and motor function. Olanzapine was also associated with more frequent reports of weight gain and significantly greater VA costs, ranging from $3000 to $9000 annually. Differences in societal costs were somewhat smaller and were not significant. Conclusion Olanzapine does not demonstrate advantages compared with haloperidol (in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost. C1 Dept Vet Affairs Med Ctr, West Haven, CT USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Dept Vet Affairs, Cooperat Studies Program, Coordinating Ctr, Perry Point, MD USA. Dept Vet Affairs Med Ctr, Albuquerque, NM USA. Dept Vet Affairs, Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA. Dept Vet Affairs Med Ctr, Montrose, NY USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, New York, NY USA. Dept Vet Affairs Med Ctr, Tuscaloosa, AL USA. Dept Vet Affairs Med Ctr, Miami, FL USA. Dept Vet Affairs Med Ctr, Durham, NC USA. Dept Vet Affairs Med Ctr, Augusta, GA USA. Dept Vet Affairs Med Ctr, Bay Pines, FL USA. Dept Vet Affairs Med Ctr, Detroit, MI USA. Dept Vet Affairs Med Ctr, Bedford, MA USA. Dept Vet Affairs Med Ctr, Brecksville, OH USA. Howard Univ, Sch Med, Washington, DC 20059 USA. Dept Vet Affairs Med Ctr, Tuskegee, AL USA. Dept Vet Affairs Med Ctr, Palo Alto, CA USA. Dept Vet Affairs Med Ctr, Lyons, NJ USA. Dept Vet Affairs Med Ctr, Indianapolis, IN USA. RP Rosenheck, R (reprint author), VA Connecticut Hlth Care Syst, NE Program Evaluat Ctr 182, 950 Campbell Ave, West Haven, CT 06516 USA. OI Lawson, William/0000-0002-9324-7090 FU NCI NIH HHS [R25 CA092049] NR 62 TC 249 Z9 262 U1 3 U2 12 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 NOV 26 PY 2003 VL 290 IS 20 BP 2693 EP 2702 DI 10.1001/jama.290.20.2693 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 747CR UT WOS:000186788100021 PM 14645311 ER PT J AU Lombardo, JA Stern, EA McLellan, ME Kajdasz, ST Hickey, GA Bacskai, BJ Hyman, BT AF Lombardo, JA Stern, EA McLellan, ME Kajdasz, ST Hickey, GA Bacskai, BJ Hyman, BT TI Amyloid-beta antibody treatment leads to rapid normalization of plaque-induced neuritic alterations SO JOURNAL OF NEUROSCIENCE LA English DT Article DE immunotherapy; antibody; plasticity; neurodegeneration; amyloid ID ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; TRANSGENIC MICE; IN-VIVO; NEUROPIL CHANGES; NEURONAL LOSS; PLASTICITY; NEUROPATHOLOGY; ABNORMALITIES; DISRUPTION AB The accumulation of amyloid-beta into insoluble plaques is a characteristic feature of Alzheimer's disease. Neuronal morphology is distorted by plaques: rather than being essentially straight, they are substantially more curved than those in control tissue, their trajectories become altered, and they are frequently distended or swollen, presumably affecting synaptic transmission. Clearance of plaques by administration of antibodies to amyloid-beta is a promising therapeutic approach to the treatment of Alzheimer's disease, leading to stabilization of dementia by an unknown cellular mechanism. The effect of plaque clearance on plaque-induced neuronal alterations has not been studied previously. Here we show that both plaques and neuritic lesions are reversible in a strikingly short period of time after administration of a single dose of amyloid-beta antibody. Amyloid clearance and recovery of normal neuronal geometries were observed as early as 4d and lasted at least 32 d after a single treatment. These results demonstrate that, once plaques are cleared, neuronal morphology is self-correcting and that passive antibody treatment has the potential to reverse neuronal damage caused by Alzheimer's disease and, hence, directly impact cognitive decline. Moreover, the rapid normalization of neuritic dystrophy suggests an unexpected degree of plasticity in the adult nervous system. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimer Unit, Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimer Unit, Ctr Aging Genet & Neurodegenerat, 114 16th St,CAGN 2009, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG020570, AG15453, AG08487]; NIBIB NIH HHS [EB00768] NR 20 TC 125 Z9 131 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 26 PY 2003 VL 23 IS 34 BP 10879 EP 10883 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 749DC UT WOS:000186902500017 PM 14645482 ER PT J AU Tajouri, L Mellick, AS Ashton, KJ Tannenberg, AEG Nagra, RM Tourtellotte, WW Griffiths, LR AF Tajouri, L Mellick, AS Ashton, KJ Tannenberg, AEG Nagra, RM Tourtellotte, WW Griffiths, LR TI Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis SO MOLECULAR BRAIN RESEARCH LA English DT Article DE multiple sclerosis; plaque; chronic active; acute; cDNA microarray; quantitative PCR analysis ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; POLYMERASE-CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; MICROARRAY ANALYSIS; PARKINSONS-DISEASE; OXIDATIVE STRESS; PROTEIN; LESIONS; RECEPTOR; CLONING AB Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS with both genetic and environmental contributing factors. Clinical symptoms are broadly characterized by initial onset, and progressive debilitating neurological impairment. In this study, RNA from MS chronic active and MS acute lesions was extracted, and compared with patient matched normal white matter by fluorescent cDNA microarray hybridization analysis. This resulted in the identification of 139 genes that were differentially regulated in MS plaque tissue compared to normal tissue. Of these, 69 genes showed a common pattern of expression in the chronic active and acute plaque tissues investigated (P-value < 0.0001, rho = 0.73, by Spearman's rho analysis); while 70 transcripts were uniquely differentially expressed (greater than or equal to 1.5-fold) in either acute or chronic active tissues. These results included known markers of MS such as the myelin basic protein (MBP) and glutathione S-transferase (GS7) M1, nerve growth factors, such as nerve injury-induced protein 1 (NINJ1), X-ray and excision DNA repair factors (XRCC9 and ERCC5) and X-linked genes such as the ribosomal protein, RPS4X. Primers were then designed for seven array-selected genes, including transferrin (TF), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), GSTP1, crystallin, alpha-B (CRYAB), phosphomannomutase 1 (PMM1) and tubulin beta-5 (TBB5), and real time quantitative (Q)-PCR analysis was performed. The results of comparative Q-PCR analysis correlated significantly with those obtained by array analysis (r = 0.75, P-value < 0.01, by Pearson's bivariate correlation). Both chronic active and acute plaques shared the majority of factors identified suggesting that quantitative, rather than gross qualitative differences in gene expression pattern may define the progression from acute to chronic active plaques in MS. (C) 2003 Elsevier B.V. All rights reserved. C1 Griffith Univ, Sch Hlth Sci, Southport, Qld 4215, Australia. Queensland Med Labs, West End, Qld 4101, Australia. W Los Angeles Vet Affairs Med Ctr, Human Brain & Spinal Fluid Resources Ctr, Los Angeles, CA 90073 USA. RP Griffiths, LR (reprint author), Genome Res Ctr, Sch Hlth Sci, PMB 50 GCMC, Griffith, NSW 9726, Australia. RI Ashton, Kevin/R-2147-2016; OI Ashton, Kevin/0000-0001-6106-3425; Mellick, Albert/0000-0002-0668-2706; Griffiths, Lyn/0000-0002-6774-5475 NR 84 TC 71 Z9 71 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV 26 PY 2003 VL 119 IS 2 BP 170 EP 183 DI 10.1016/j.molbrainres.2003.09.008 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 748FV UT WOS:000186852600006 ER PT J AU Cook, SA Morissette, M Matsui, T Nagoshi, T Molkentin, JD Rosenzweig, A AF Cook, SA Morissette, M Matsui, T Nagoshi, T Molkentin, JD Rosenzweig, A TI Myostatin regulates cardiomyocyte growth in vitro and in vivo SO CIRCULATION LA English DT Meeting Abstract CT 74th Annual Scientific Sessions of the American-Heart-Association CY NOV 11-14, 2001 CL ANAHEIM, CALIFORNIA SP Amer Heart Assoc C1 Cinncinnati Childrens Hosp, Med Ctr, Div Mol Cardiovasc Biol, Cincinnati, OH USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 25 PY 2003 VL 108 IS 21 MA 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 746VL UT WOS:000186768300043 ER PT J AU Shaw, SY Peterson, TA Milan, DJ Zhong, TP MacRae, CA Schreiber, SL Fishman, MC Peterson, RT AF Shaw, SY Peterson, TA Milan, DJ Zhong, TP MacRae, CA Schreiber, SL Fishman, MC Peterson, RT TI Discovery of a novel pro-vasculogenic small molecule via a chemical genetic screen for suppressors of zebrafish gridlock mutants SO CIRCULATION LA English DT Meeting Abstract CT 74th Annual Scientific Sessions of the American-Heart-Association CY NOV 11-14, 2001 CL ANAHEIM, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Vanderbilt Univ Sch Med, Nashville, TN USA. Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Novartis Inst BioMed Rsch, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 25 PY 2003 VL 108 IS 21 MA 5 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 746VL UT WOS:000186768300046 ER PT J AU Gutmann, DH James, CD Poyhonen, M Louis, DN Ferner, R Guha, A Hariharan, S Viskochil, D Perry, A AF Gutmann, DH James, CD Poyhonen, M Louis, DN Ferner, R Guha, A Hariharan, S Viskochil, D Perry, A TI Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1 SO NEUROLOGY LA English DT Article ID NF1-ASSOCIATED PILOCYTIC ASTROCYTOMAS; GENE-EXPRESSION; NEUROFIBROMATOSIS TYPE-1; PHENOTYPE; MUTATIONS; CHILDREN; GLIOMAS; TUMORS AB Background: Fifteen to 20% of children with neurofibromatosis type 1 (NF1) develop low-grade astrocytomas. Although brain tumors are less common in teenagers and adults with NF1, recent studies have suggested that patients with NF1 are at a significantly increased risk of developing astrocytomas. Objectives: To investigate the genetic basis for astrocytoma development in patients with NF1 beyond the first decade of life. Methods: The authors performed molecular genetic analyses of 10 NF1-associated astrocytomas representing all World Health Organization (WHO) malignancy grades using fluorescence in situ hybridization, loss of heterozygosity, immunohistochemistry, and direct sequencing. Results: Later-onset NF1-associated astrocytomas, unlike histologically identical sporadic astrocytomas, exhibit NF1 inactivation, supporting a direct association with NF1 rather than a chance occurrence. Furthermore, some of these astrocytomas have homozygous NF1 deletion. In addition, genetic changes observed in high-grade sporadic astrocytomas, including TP53 mutation and CDKN2A/p16 deletion, are also seen in NF1-associated high-grade astrocytomas. Conclusions: Neurofibromatosis type 1-associated astrocytomas occurring in patients older than 10 years exhibit genetic changes observed in sporadic high-grade astrocytomas. Patients with neurofibromatosis type 1 and germline NF1 deletions may be at risk for developing late-onset astrocytomas. C1 Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Family Federat Finland, Dept Med Genet, Helsinki, Finland. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Guys & St Thomas Hosp Trust, Dept Neurol, London, England. Univ Toronto, Dept Neurosurg, Toronto, ON, Canada. Seton Hall Univ, Dept Neurol, Edison, NJ 08818 USA. Univ Utah, Dept Pediat, Div Med Genet, Salt Lake City, UT 84112 USA. RP Gutmann, DH (reprint author), Washington Univ, Sch Med, Dept Neurol, Box 8111,660 S Euclid Ave, St Louis, MO 63110 USA. RI James, Charles/E-2721-2012; OI James, Charles/0000-0002-1027-203X; Perry, Arie/0000-0002-8300-7261 FU NINDS NIH HHS [NS36996] NR 21 TC 36 Z9 39 U1 2 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 NOV 25 PY 2003 VL 61 IS 10 BP 1397 EP 1400 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 746VF UT WOS:000186767800017 PM 14638962 ER PT J AU Handforth, A Ondo, WG Tatter, S Mathern, GW Simpson, RK Walker, F Sutton, JP Hubble, JP Jankovic, J AF Handforth, A Ondo, WG Tatter, S Mathern, GW Simpson, RK Walker, F Sutton, JP Hubble, JP Jankovic, J TI Vagus nerve stimulation for essential tremor - A pilot efficacy and safety trial SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HARMALINE-INDUCED TREMOR; SYSTEM; CEREBELLUM; VAGAL; REPRESENTATION; SEIZURES; CAT AB Objective: To assess the safety and efficacy of vagus nerve stimulation (VNS) for essential tremor (ET). Methods: This was a pilot open-treatment trial at three centers, with masked videotape tremor assessments. Inclusion required a severity score of 3 or 4 on the Tremor Rating Scale (TRS) in one or both hands. At baseline, tremor was assessed with TRS and Unified Tremor Rating Assessment (UTRA), accelerometry, and a videotape protocol. The VNS device was implanted with leads placed around the left cervical vagus nerve. Stimulation was adjusted over 4 weeks before the repeat tremor assessments. Two raters masked to the study visit scored the videotapes. Results: Nine subjects participated, with a mean age of 65 years and a mean age at onset of tremor of 24. Investigators rated hand tremor as mildly improved (TRS 2.3+/-0.7 during VNS vs 3.0+/-0.4 during baseline, p=0.06). Accelerometry-measured total power improved 50.2+/-31.8% (p<0.01). Videotape tremor scores were highly correlated between the masked raters and revealed no changes in tremor scores with treatment. VNS was well tolerated, with the most common adverse events being stimulation related. Conclusions: VNS was judged by investigators to mildly improve upper extremity tremor. This finding was not confirmed in videotape scoring by masked raters. VNS is not likely to have a clinically meaningful effect on ET. C1 Vet Affairs Greater Los angeles Healthcare Syst, Neurol Serv W127, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Calif Neurosci Inst, Oxnard, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Ohio State Univ, Columbus, OH 43210 USA. RP Handforth, A (reprint author), Vet Affairs Greater Los angeles Healthcare Syst, Neurol Serv W127, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 18 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 NOV 25 PY 2003 VL 61 IS 10 BP 1401 EP 1405 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 746VF UT WOS:000186767800018 PM 14638963 ER PT J AU Coser, KR Chesnes, J Hur, JY Ray, S Isselbacher, KJ Shioda, T AF Coser, KR Chesnes, J Hur, JY Ray, S Isselbacher, KJ Shioda, T TI Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID E-SCREEN ASSAY; EXPRESSION PROFILES; RESPONSE ELEMENTS; PROTEIN FHL2; RECEPTOR; ACTIVATION; TRANSCRIPTION; IDENTIFICATION; COACTIVATOR; PROGRESSION AB To obtain comprehensive information on 17beta-estradiol (E2) sensitivity of genes that are inducible or suppressible by this hormone, we designed a method that determines ligand sensitivities of large numbers of genes by using DNA microarray and a set of simple Perl computer scripts implementing the standard metric statistics. We used it to characterize effects of low (0-100 pM) concentrations of E2 on the transcriptome profile of MCF7/BUS human breast cancer cells, whose E2 dose-dependent growth curve saturated with 100 pM E2. Evaluation of changes in mRNA expression for all genes covered by the DNA microarray indicated that, at a very low concentration (10 pM), E2 suppressed approximate to3-5 times larger numbers of genes than it induced, whereas at higher concentrations (30-100 pM) it induced approximate to1.5-2 times more genes than it suppressed. Using clearly defined statistical criteria, E2-inducible genes were categorized into several classes based on their E2 sensitivities. This approach of hormone sensitivity analysis revealed that expression of two previously reported E2-inducible autocrine growth factors, transforming growth factor alpha and stromal cell-derived factor 1, was not affected by 100 pM and lower concentrations of E2 but strongly enhanced by 10 nM E2, which was far higher than the concentration that saturated the E2 dose-dependent growth curve of MCF7/BUS cells. These observations suggested that biological actions of E2 are derived from expression of multiple genes whose E2 sensitivities differ significantly and, hence, depend on the E2 concentration, especially when it is lower than the saturating level, emphasizing the importance of characterizing the ligand dose-dependent aspects of E2 actions. C1 Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, DNA Microarray Core Facil, Charlestown, MA 02129 USA. XMine Inc, Brisbane, CA 94005 USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA082230, R01-CA82230] NR 27 TC 105 Z9 109 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 2003 VL 100 IS 24 BP 13994 EP 13999 DI 10.1073/pnas.2235866100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800046 PM 14610279 ER PT J AU Katz, SG Williams, A Yang, JF Fujiwara, Y Tsang, AP Epstein, JA Orkin, SH AF Katz, SG Williams, A Yang, JF Fujiwara, Y Tsang, AP Epstein, JA Orkin, SH TI Endothelial lineage-mediated loss of the GATA cofactor friend of GATA 1 impairs cardiac development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GATA-4; neural crest; endothelium; double outlet right ventricle; cardiogenesis ID TRANSCRIPTION FACTOR GATA-1; ZINC-FINGER PROTEIN; VASCULAR DEVELOPMENT; HEMATOPOIETIC-CELLS; HEART MORPHOGENESIS; NEURAL CREST; MICE LACKING; IN-VIVO; DIFFERENTIATION; EXPRESSION AB GATA transcription factors, together with Friend of GATA (FOG) cofactors, are required for the differentiation of diverse cell types. Multiple aspects of hematopoiesis are controlled by the interaction of FOG-1 with the GATA-1/2/3 subfamily. Likewise, FOG-2 is co-expressed with the GATA-4/5/6 subfamily at other sites, including the heart and gonads. FOG-2 and GATA-4 are required for cardiac development. Through transgenic rescue of hematopoietic defects of FOG-1(-/-) embryos we define an unsuspected role for FOG-1 in heart development. In particular, rescued FOG-1-/- mice die at embryonic day (E) 14.5 with cardiac defects that include double outlet right ventricle and a common atrioventricular valve. Using conditional inactivation of Fog-1 we assign the cell of origin in which FOG-1 function is required. Neural crest cells migrate properly into FOG-1-/- hearts and mice with FOG-1 conditionally excised from neural crest derivatives fail to develop cardiac abnormalities. In contrast, conditional inactivation of FOG-1 in endothelial-derived tissues by means of Tie-2-expressed Cre recapitulates the rescue-knockout defects. These findings establish a nonredundant requirement for FOG-1 in the outlet tract and atrioventricular valves of the heart that depend on expression in endothelial-derived tissue and presumably reflect cooperation with the GATA-4/5/6 subfamily. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Penn, Hlth Syst, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA. Univ Penn, Hlth Syst, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. NR 41 TC 30 Z9 32 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 NOV 25 PY 2003 VL 100 IS 24 BP 14030 EP 14035 DI 10.1073/pnas.1936250100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800052 PM 14614148 ER PT J AU Lin, JY DeCaprio, JA AF Lin, JY DeCaprio, JA TI SV40 large T antigen promotes dephosphorylation of p130 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIMIAN-VIRUS-40 LARGE-T; RETINOBLASTOMA SUSCEPTIBILITY GENE; PROTEIN PHOSPHATASE 2A; PRB-RELATED PROTEINS; SMALL TUMOR-ANTIGEN; HEAT-SHOCK PROTEIN; DNA-REPLICATION; CELL-CYCLE; OKADAIC ACID; J-DOMAIN AB SV40 large T antigen ( Ag) binds to all members of the retinoblastoma ( RB) tumor suppressor family including pRb, p107, and p130. Although the LXCXE motif of T Ag binds directly to the RB proteins, it is not sufficient to fully inactivate their function. The N- terminal DNA J domain of T Ag cooperates with the LXCXE motif to override RB- mediated repression of E2F- dependent transcription. In addition, T Ag can reduce the overall phosphorylation state of p107 and p130 that is dependent on an intact J domain and LXCXE motif. However, the mechanism of this activity has not been described. Here we describe the use of a cell- free system to characterize the effect of T Ag on p130 phosphorylation. When incubated in extracts prepared from S phase cells, p130 undergoes specific phosphorylation. Addition of T Ag to S phase extracts leads to a reduction of p130 phosphorylation in vitro. The ability of T Ag to reduce the phosphorylation of p130 in vitro is dependent on an intact DNA J domain and can be inhibited by okadaic acid and PP2A- specific inhibitors. These results suggest that T Ag recruits a phosphatase activity in a DNA J domain- dependent manner to reduce the phosphorylation of p130. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 457,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 063113] NR 62 TC 18 Z9 18 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 NOV 21 PY 2003 VL 278 IS 47 BP 46482 EP 46487 DI 10.1074/jbc.M307044200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400033 PM 12968030 ER PT J AU Guiot, C Degiorgis, PG Delsanto, PP Gabriele, P Deisboeck, TS AF Guiot, C Degiorgis, PG Delsanto, PP Gabriele, P Deisboeck, TS TI Does tumor growth follow a "universal law"? SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE tumor growth kinetics; tumor therapy; methametical modelling; universal law; metastasis; angiogenesis; invasion ID CANCER GROWTH; IN-VIVO; MODEL; ANGIOGENESIS; METASTASIS; SPHEROIDS; BRAIN; CELLS; TIME AB A general model for the ontogenetic growth of living organisms has been recently proposed. Here we investigate the extension of this model to the growth of solid malignant tumors. A variety of in vitro and in vivo data are analysed and compared with the prediction of a "universal" law, relating properly rescaled tumor masses and tumor growth times. The results support the notion that tumor growth follows such a universal law. Several important implications of this finding are discussed, including its relevance for tumor metastasis and recurrence, cell turnover rates, angiogenesis and invasion. (C) 2003 Published by Elsevier Ltd. C1 Univ Turin, INFM, Dept Neurosci, I-10125 Turin, Italy. Sez Torino Univ & Politecn, INFM, Turin, Italy. Politecn Torino, Dip Fis, Turin, Italy. IRCC Candiolo, Turin, Italy. Harvard Univ, HST Biomed Engn Ctr, Athinula A Martinos Ctr Biomed Imaging, MIT,Complex Biosyst Modeling Lab, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab, Boston, MA 02129 USA. RP Guiot, C (reprint author), Univ Turin, INFM, Dept Neurosci, C Raffaello 30, I-10125 Turin, Italy. EM caterina.guiot@unito.it RI guiot, caterina/C-6708-2009; OI guiot, caterina/0000-0001-8529-1625; Gabriele, Pietro/0000-0002-1792-2525 NR 25 TC 147 Z9 151 U1 0 U2 13 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD NOV 21 PY 2003 VL 225 IS 2 BP 147 EP 151 DI 10.1016/S0022-5193(03)00221-2 PG 5 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 740CB UT WOS:000186382300001 PM 14575649 ER PT J AU Garg, HG Yu, LY Hales, CA Toida, T Islam, T Linhardt, RJ AF Garg, HG Yu, LY Hales, CA Toida, T Islam, T Linhardt, RJ TI Sulfation patterns in heparin and heparan sulfate: effects on the proliferation of bovine pulmonary artery smooth muscle cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE heparin; heparan sulfate; smooth muscle cell; proliferation; post-column derivatization HPLC; H-1 NMR ID ANTIPROLIFERATIVE ACTIVITY; STRUCTURAL DETERMINANTS; DERMATAN SULFATE; PROTEOGLYCANS; GLYCOSAMINOGLYCANS; DESULFATION; CAPACITY; INHIBIT AB Heparin's (HP's) antiproliferative effect on smooth muscle cells is potentially important in defining new approaches to treat pulmonary hypertension. The commercially available HP and heparan sulfate (HS) are structurally heterogenous polymers. In order to examine which sulfonate groups are required for endogenous antiproliferative activity, we prepared the following six chemically modified porcine mucosal HP and HS, which fell into three groups. One group consisted of fully O-sulfonated-N-acetylated, the second group consisted of de-N-sulfonated and re-N-acetylated, and the third group consisted of 6-O-desulfonated HP and HS derivatives. These six preparations were assayed for their antiproliferative potency on bovine pulmonary artery smooth muscle cells. The results of this assay show that (a) over-O-sulfonation of both HP and HS increases antiproliferative activity, (b) substitution of hexosamine with N-acetyl diminishes antiproliferative activity in both HP and HS, and (c) 6-O-desulfonation of HP and HS diminishes antiproliferative potency. Surprisingly, the type of uronic acid residue present at a given level of sulfation is unimportant for antiproliferative potency. In conclusion, only the level of O- and N-sulfo group substitution correlates well with HP and HS antiproliferative activity. (C) 2003 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm Crit Care Unit, Boston, MA 02114 USA. Chiba Univ, Fac Pharmaceut Sci, Inage Ku, Chiba 2638522, Japan. Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. Rensselaer Polytech Inst, Dept Biol & Chem, Troy, NY 12180 USA. RP Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm Crit Care Unit, Boston, MA 02114 USA. EM HGARG@PARTNERS.ORG FU NHLBI NIH HHS [R01 HL039150] NR 22 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 EI 0006-3002 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD NOV 20 PY 2003 VL 1639 IS 3 BP 225 EP 231 DI 10.1016/j.bbadis.2003.09.002 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 748FP UT WOS:000186852100010 PM 14636954 ER PT J AU Korey, CA MacDonald, ME AF Korey, CA MacDonald, ME TI An over-expression system for characterizing Ppt1 function in Drosophila SO BMC NEUROSCIENCE LA English DT Article ID PALMITOYL-PROTEIN THIOESTERASE; NEURONAL CEROID-LIPOFUSCINOSIS; CELL-DEATH; RAS AB Background: The infantile onset form of Neuronal Ceroid Lipofuscinoses (INCL) is the earliest and most severe form of NCL, with neurological symptoms that reflect massive neurodegeneration in the CNS and retina. INCL is due to recessively inherited mutations at the CLN1 locus. This locus encodes the evolutionarily conserved enzyme palmitoyl-protein thioesterase 1 (PPT1), indicating an essential role for protein palmitoylation in normal neuronal function. Results: To begin to elucidate the specific role that Ppt1 plays in neuronal cells, we have developed a Ppt1 over-expression system in Drosophila. We report that over-expression of DmPpt1 in the developing Drosophila visual system leads to the loss of cells through apoptotic cell death. This DmPpt1 over-expression phenotype is suppressed by DmPpt1 genomic deficiencies. Moreover, over-expression of DmPpt1S123A, which bears a catalytic site serine 123 to alanine mutation, does not lead to the severe eye phenotype observed with over-expression of wild-type DmPpt1. Thus, cell loss in DmPpt1 flies is directly related to the dosage of wildtype DmPpt1. Conclusions: Although INCL is due to the loss of PPT1; increased levels of DmPpt1 also lead to neurodegeneration possibly via a detrimental effect on some aspect of PPT1's normal function. This suggests that the precise levels of PPT1 activity are important for neuronal cell survival. The Drosophila DmPpt1 over-expression system provides a resource for genetic experiments that aim to identify the processes by which PPT1 regulates the palmitoylation-state of its essential protein substrates. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Coll Charleston, Dept Biol, Charleston, SC 29424 USA. RP Korey, CA (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS033648, R01 NS033648] NR 21 TC 30 Z9 31 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD NOV 20 PY 2003 VL 4 AR 30 DI 10.1186/1471-2202-4-30 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 752ZZ UT WOS:000187207600001 PM 14629778 ER PT J AU Singh, AK Harris, NL Bazari, H Steele, DJR Colvin, RB AF Singh, AK Harris, NL Bazari, H Steele, DJR Colvin, RB TI A 68-year-old woman with impaired renal function - Acute granulomatous interstitial nephritis with tubular injury and minimal-change disease, due to a reaction to ibuprofen. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; THE-COUNTER IBUPROFEN; NEPHROTIC SYNDROME; GLOMERULONEPHRITIS; PROTEINURIA; FAILURE; HYPERSENSITIVITY; THERAPY C1 Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Singh, AK (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. NR 30 TC 10 Z9 10 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 20 PY 2003 VL 349 IS 21 BP 2055 EP 2063 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 744QE UT WOS:000186642900011 PM 14627791 ER PT J AU Hideshima, T Chauhan, D Hayashi, T Akiyama, M Mitsiades, N Mitsiades, C Podar, K Munshi, NC Richardson, PG Anderson, KC AF Hideshima, T Chauhan, D Hayashi, T Akiyama, M Mitsiades, N Mitsiades, C Podar, K Munshi, NC Richardson, PG Anderson, KC TI Proteasome inhibitor PS-341 abrogates IL-6 triggered signaling cascades via caspase-dependent downregulation of gp130 in multiple myeloma SO ONCOGENE LA English DT Article DE multiple myeloma; proteasome inhibitor; IL-6; gp130; caspase ID ACTIVATED PROTEIN-KINASE; MARROW STROMAL CELLS; DEXAMETHASONE-INDUCED APOPTOSIS; NF-KAPPA-B; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; THERAPEUTIC APPLICATIONS; MOLECULAR-MECHANISMS; DRUG-RESISTANCE; UP-REGULATION; PLASMA-CELLS AB Proteasome inhibitor PS-341 is one of the most promising novel agents against multiple myeloma (MM). We have previously shown that PS-341 inhibits IL-6 triggered phosphorylation of extracellular signal-regulated kinases (ERK) 1/2 (also known as p42/44 mitogen-activated protein kinases) in MM cells. In this study, we further examined whether clinically achievable concentrations of PS-341 could inhibit IL-6 triggered signaling cascades in MM. We found that PS-341 inhibited not only ERK, but also signal transducers and activators of transcription (STAT) 3 as well as Akt phosphorylation. Since gp130 (CD130) dimerizes and is phosphorylated after IL-6 binding to gp80 (IL-6 receptor), we hypothesized that gp130 could be involved in PS-341-induced blockade of signaling cascades mediating MM cell growth, survival, and drug resistance in the bone marrow (BM) microenvironment. In this study, we first demonstrate that PS-341 induces downregulation of gp130 in a time- and dose-dependent manner in vitro, prior to MM cell death. Conversely, downregulation of gp130 is completely abrogated by the pan-caspase inhibitor Z-VAD-FMK, suggesting that downregulation of gp130 is mediated via caspase activation. Z-VAD-FMK also abrogates the inhibitory effect of PS-341 on IL-6-triggered signaling cascades. Importantly, we demonstrate that phosphorylation of ERK, STAT3, and Akt in MM.1S cells induced by either exogenous IL-6 or by binding of MM cells to BM stromal cells is abrogated by PS-341. These studies, therefore, define another novel mechanism whereby PS-341 can overcome the growth and survival advantage in MM cells conferred by the BM milieu. Importantly, this effect on cytokine-induced gp130 signaling cascades may account, at least in part, for the remarkable preclinical sensitivity and clinical responses achieved in MM with PS-341 treatment. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer 557,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R0-1 CA 50947]; PHS HHS [P0-1 78378] NR 44 TC 122 Z9 126 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 20 PY 2003 VL 22 IS 52 BP 8386 EP 8393 DI 10.1038/sj.onc.1207170 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 744UB UT WOS:000186650300002 PM 14627979 ER PT J AU Waisbren, SE Albers, S Amat, S Ampola, M Brewster, TG Demmer, L Eaton, RB Greenstein, R Korson, M Larson, C Marsden, D Msall, M Naylor, EW Pueschel, S Seashore, M Shih, VE Levy, HL AF Waisbren, SE Albers, S Amat, S Ampola, M Brewster, TG Demmer, L Eaton, RB Greenstein, R Korson, M Larson, C Marsden, D Msall, M Naylor, EW Pueschel, S Seashore, M Shih, VE Levy, HL TI Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TANDEM MASS-SPECTROMETRY; INBORN-ERRORS; DEFICIENCY; METABOLISM; INFANTS; PROGRAM; HEALTH; TESTS AB Context Tandem mass spectrometry now allows newborn screening for more than 20 biochemical genetic disorders. Questions about the effectiveness and risks of expanded newborn screening for biochemical genetic disorders need to be answered prior to its widespread acceptance as a state-mandated program. Objectives To compare newborn identification by expanded screening with clinical identification of biochemical genetic disorders and to assess the impact on families of a false-positive screening result compared with a normal result in the expanded newborn screening program. Design Prospective study involving an inception cohort of newly diagnosed children. Setting Massachusetts, Maine, and a private laboratory in Pennsylvania with expanded newborn screening; other New England states with limited screening. Participants Families of 50 affected children identified through expanded newborn screening (82% of eligible cases); 33 affected children identified clinically (97% of eligible cases); 94 screened children with false-positive results (75% of eligible cases); and 81 screened children with normal results (63% of eligible cases). Main Outcome Measures Child's health and development and the Parental Stress Index. Results Within the first 6 months of life, 28% of children identified by newborn screening compared with 55% of clinically identified children required hospitalization (P=.02). One child identified by newborn screening compared with 8 (42%) identified clinically performed in the range of mental retardation (P<.001). Mothers in the screened group reported lower overall stress on the Parental Stress Index than mothers in the clinically identified group (z=3.38, P<.001). Children with false-positive results compared with children with normal results were twice as likely to experience hospitalization (21% [n=20] vs 10% [n=8], respectively; P=.06). Mothers of children in the false-positive group compared with mothers of children with normal screening results attained higher scores on the Parental Stress Index (z=4.25, P<.001) and the Parent-Child Dysfunction subscale (z=5.30, P<.001). Conclusions Expanded newborn screening may lead to improved health outcomes for affected children and lower stress for their parents. However, false-positive screening results may place families at risk for increased stress and parent-child dysfunction. C1 Childrens Hosp Boston, Boston, MA 02115 USA. Univ Munster, D-4400 Munster, Germany. Eastern Maine Med Ctr, Bangor, ME USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Maine Med Ctr, Portland, ME 04102 USA. Univ Massachusetts, Sch Med, New England Newborn Screening Program, Jamaica Plain, MA USA. Rhode Isl Hosp, Providence, RI USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Pediat Screening Inc, Bridgeville, PA USA. Yale Univ, Sch Med, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Waisbren, SE (reprint author), Childrens Hosp Boston, IC Smith 108,300 Longwood Ave, Boston, MA 02115 USA. FU NHGRI NIH HHS [R01 HG02085]; PHS HHS [5H46 MC 00158] NR 39 TC 176 Z9 180 U1 2 U2 7 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 NOV 19 PY 2003 VL 290 IS 19 BP 2564 EP 2572 DI 10.1001/jama.290.19.2564 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 744DQ UT WOS:000186613000026 PM 14625333 ER PT J AU Hallows, JL Chen, K DePinho, RA Vincent, I AF Hallows, JL Chen, K DePinho, RA Vincent, I TI Decreased cyclin-dependent kinase 5 (cdk5) activity is accompanied by redistribution of cdk5 and cytoskeletal proteins and increased cytoskeletal protein phosphorylation in p35 null mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cdk5; p35; tau phosphorylation; neurofilament phosphorylation; MAP2 phosphorylation; cytoskeletal pathology; trafficking transport ID GLYCOGEN-SYNTHASE KINASE-3-BETA; AMYOTROPHIC-LATERAL-SCLEROSIS; MICROTUBULE-ASSOCIATED PROTEINS; GLIAL CYTOPLASMIC INCLUSIONS; MULTIPLE SYSTEM ATROPHY; NEUROFIBRILLARY TANGLES; TAU PHOSPHORYLATION; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; ACTIVATOR P35 AB Cdk5/p35 has been implicated in cytoskeletal protein phosphorylation in normal brain and in many human neurodegenerative disorders. Yet, mouse models of cdk5/p35 hyperactivity have not yielded corresponding changes in cytoskeletal protein phosphorylation. To elucidate the relationship between p35, cdk5, and the neuronal cytoskeleton, we deleted the p35 gene in mice having a pure C57BL/6 background. We found that p35 deficiency leads to a 38% reduction of cdk5 activity in adult brain. In addition, loss of p35 causes an anterograde redistribution of cdk5 toward peripheral neuronal processes. The unusual presence of nonphosphorylated neurofilament (NF) in aberrant axon fascicles and the relocation of tau and MAP2B from cell bodies and proximal neuronal processes to more distal sites of the neuropil in p35-/- mouse brain implicate p35 in neuronal trafficking, particularly in dynein-driven retrograde transport. In many axons of normal brain, cdk5 fails to colocalize with phosphorylated cytoskeletal protein epitopes. This observation, together with an unexpected increase of NF, tau, and MAP2B phosphoepitopes accompanying the decreased cdk5 activity in p35-/- mice, supports the idea that cdk5 does not phosphorylate cytoskeletal proteins directly. Rather, in structures where cdk5 does colocalize with phosphorylated cytoskeletal protein epitopes, it may function as a negative regulator of other proline-directed kinases that directly phosphorylate the proteins. Evidence for increased glycogen synthase kinase 3beta(GSK3beta) activity in p35-/- mice suggests that GSK3beta maybe one such kinase regulated by cdk5. Our studies illustrate that p35 regulates the subcellular distribution of cdk5 and cytoskeletal proteins in neurons and that cdk5 has a hierarchical role in regulating the phosphorylation and function of cytoskeletal proteins. C1 Univ Washington, Nathan Shock Ctr Excellence Basic Biol Aging, Seattle, WA 98195 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Immunol, Bronx, NY 10461 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Vincent, I (reprint author), Univ Washington, Nathan Shock Ctr Excellence Basic Biol Aging, 1959 Pacific St,Box 357705, Seattle, WA 98195 USA. EM ivincent@u.washington.edu FU NIA NIH HHS [AG00057, AG12721] NR 83 TC 69 Z9 76 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 19 PY 2003 VL 23 IS 33 BP 10633 EP 10644 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 745GJ UT WOS:000186680700019 PM 14627648 ER PT J AU Rumsfeld, JS Havranek, E Masoudi, FA Peterson, ED Jones, P Tooley, JF Krumholz, HM Spertus, JA AF Rumsfeld, JS Havranek, E Masoudi, FA Peterson, ED Jones, P Tooley, JF Krumholz, HM Spertus, JA CA Cardiovascular Outcomes Res Consor TI Depressive symptoms are the strongest predictors of short-term declines in health status in patients with heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID QUALITY-OF-LIFE; CASE-FINDING INSTRUMENTS; RANDOMIZED-TRIAL; MAJOR DEPRESSION; ELDERLY PATIENTS; PRIMARY-CARE; DISEASE; RISK; OUTCOMES; CARDIOMYOPATHY AB OBJECTIVES The purpose of this study was to assess whether depressive symptoms are independently associated with changes in heart failure (HF)-specific health status. BACKGROUND Depression is common in patients with HF, but the impact of depressive symptoms on the health status of these patients over time is unknown. METHODS We conducted a multicenter prospective cohort study of outpatients with HF. Data from 460 patients who completed a baseline Medical Outcomes Study-Depression Questionnaire and both a baseline and follow-up (6 2 weeks) Kansas City Cardiomyopathy Questionnaire (KCCQ) were analyzed. The KCCQ measures HF-specific health status, including symptoms, physical and social function, and quality of life. Multivariable regression was used to evaluate depressive symptoms as a predictor of change in KCCQ scores, adjusting for baseline KCCQ scores and other patient variables. The primary outcome was change in KCCQ summary scores (range 0 to 100; higher scores indicate better health status; 5 points is a clinically meaningful change). RESULTS Approximately 30% (139/460) of the patients had significant depressive symptoms at baseline. Depressed patients had markedly lower baseline KCCQ summary scores (beta = -19.6; p < 0.001). After adjustment for potential confounders, depressed patients were at risk for significant worsening of their HF symptoms, physical and social function, and quality of life (average change in KCCQ summary score = -7.1 points; p < 0.001). Depressive symptoms were the strongest predictor of decline in health status in the multivariable, models. CONCLUSIONS Depressive symptoms are a strong predictor of short-term worsening of HF-specific health status. The recognition and treatment of depression may be an important component of HF care. (C) 2003 by the American College of Cardiology Foundation. C1 Denver VA Med Ctr, Denver, CO 80220 USA. Denver Hlth Med Ctr, Denver, CO USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ Missouri, Mid Amer Heart Inst, Columbia, MO 65211 USA. Pharmacia Corp, Skokie, IL USA. Yale Univ, Med Ctr, New Haven, CT 06520 USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, Cardiol 111B,1055 Clermont St, Denver, CO 80220 USA. FU NIA NIH HHS [KO8-AG01011] NR 36 TC 192 Z9 197 U1 1 U2 3 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 NOV 19 PY 2003 VL 42 IS 10 BP 1811 EP 1817 DI 10.1016/j.jacc.2003.07.013 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 743NW UT WOS:000186580700018 PM 14642693 ER PT J AU Kloner, RA Hutter, AM Emmick, JT Mitchell, MI Denne, J Jackson, G AF Kloner, RA Hutter, AM Emmick, JT Mitchell, MI Denne, J Jackson, G TI Time course of the interaction between tadalafil and nitrates SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ERECTILE DYSFUNCTION; SILDENAFIL CITRATE; DRUGS AB OBJECTIVES This study was designed to determine the time course of nitrate interaction with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor with a half-life (t(1/2)) of 17.5 h. BACKGROUND The PDE5 inhibitors augment the blood pressure (BP)-lowering effects of nitrates, yet the time course of this interaction is unclear. Recent guidelines from the American College of Cardiology/American Heart Association recommend that nitrates be withheld for 24 h after taking sildenafil (t(1/2) = 4 h). METHODS Male subjects (n = 150) received seven consecutive daily doses of placebo or tadalafil (20 mg). On day 7 and beyond, subjects received repeated doses of sublingual nitroglycerin (0.4 mg) after the last dose of placebo or tadalafil. After a 10- to 21-day washout period, subjects crossed over to either placebo or tadalafil, and nitrate dosing was repeated. RESULTS In response to nitroglycerin at 4, 8, and 24 h, standing systolic BP fell below 85 mm Hg in more subjects on tadalafil compared with placebo (p < 0.05), with no difference in the response to nitroglycerin at 48, 72, and 96 h (p > 0.2). Similar observations were made for standing diastolic BP <45 mm Hg, decrease in systolic BP >30 mm Hg, and decrease in diastolic BP >20 mm Hg. Nitroglycerin also evoked greater mean maximal decreases in standing systolic BP at 8 and 24 h after taking tadalafil versus placebo (p < 0.02), with no significant difference at 48, 72, or 96 h (p > 0.49). CONCLUSIONS The hemodynamic interaction between tadalafil and sublingual nitroglycerin lasted 24 h, but was not seen at 48 h and beyond. Similar to other PDE5 inhibitors, tadalafil should not be administered in combination with organic nitrates. (C) 2003 by the American College of Cardiology Foundation. C1 Univ So Calif, Keck Sch Med, Good Samaritan Hosp, Heart Inst,Cardiovasc Div, Los Angeles, CA 90017 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Erl Wood Manor, Surrey, England. Guys & St Thomas Hosp, London SE1 9RT, England. RP Kloner, RA (reprint author), Univ So Calif, Keck Sch Med, Good Samaritan Hosp, Heart Inst,Cardiovasc Div, 1225 Wilshire Blvd, Los Angeles, CA 90017 USA. RI Kloner, Robert/B-2971-2012 NR 11 TC 79 Z9 81 U1 0 U2 0 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 NOV 19 PY 2003 VL 42 IS 10 BP 1855 EP 1860 DI 10.1016/j.jacc.2003.09.023 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 743NW UT WOS:000186580700024 PM 14642699 ER PT J AU Godley, PA Schenck, AP Amamoo, MA Schoenbach, VJ Peacock, S Manning, M Symons, M Talcott, JA AF Godley, PA Schenck, AP Amamoo, MA Schoenbach, VJ Peacock, S Manning, M Symons, M Talcott, JA TI Racial differences in mortality among Medicare recipients after treatment for localized prostate cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LONG-TERM SURVIVAL; RADICAL PROSTATECTOMY; RADIATION-THERAPY; SOCIOECONOMIC-STATUS; ETHNIC-DIFFERENCES; COMORBIDITY INDEX; AFRICAN-AMERICAN; HOSPITAL VOLUME; RACE; CARE AB Background: Prostate cancer mortality is higher among black American men than among white American men. We investigated whether racial disparities in outcomes of clinically localized prostate cancer vary by treatment (surgery, radiation therapy, or nonaggressive treatment). Methods: Merged Surveillance, Epidemiology, and End Results Program (SEER) and Medicare files provided data (on treatment modality, age, race, cancer stage, tumor grade, census tract socioeconomic status, and date of death) on 5747 black and 38 242 white patients diagnosed at age 65-84 years with clinically localized prostate cancer between 1986 and 1996 in five SEER sites. Patients were followed through 1998. Racial differences in survival outcomes were assessed using Kaplan-Meier survival curves and Cox regression models. Results: The median survival time for black patients was 1.7 years (95% confidence interval [CI] = 1.6 to 1.9 years) less than that for white patients. Median survival in black patients relative to white patients was 1.8 years (95% CI = 1.5 to 2.0 years) less among those who had surgery, 0.7 years (95% CI = 0.5 to 1.0 years) less among those who had radiation therapy, and 1.0 years (95% CI = 0.7 to 1.1 years) less among those who had nonaggressive treatment. Racial disparities were evident both in overall survival and in prostate cancer-specific survival, before and after statistical adjustment for covariates. Conclusions: Black patients' poorer overall survival from localized prostate cancer varies by initial treatment, with the survival gap being largest among patients undergoing surgery. Investigating these treatment-specific differences may clarify the mechanisms underlying worse outcomes for black patients in the health care system. C1 Univ N Carolina, Div Hematol Oncol, Sch Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC USA. Univ N Carolina, Program Ethn Culture & Hlth Outcomes, Chapel Hill, NC USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. Med Review N Caroline Inc, Cary, NC USA. Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Godley, PA (reprint author), Univ N Carolina, Div Hematol Oncol, Sch Med, 3009 Old Clin Bldg,CB 7305, Chapel Hill, NC 27599 USA. FU NIMHD NIH HHS [1 P60 MD00244-01]; ODCDC CDC HHS [U48/CCU409660] NR 54 TC 80 Z9 80 U1 2 U2 2 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 NOV 19 PY 2003 VL 95 IS 22 BP 1702 EP 1710 DI 10.1093/jnci/djg094 PG 9 WC Oncology SC Oncology GA 747JF UT WOS:000186800900011 PM 14625261 ER PT J AU Ackermann, RT Carroll, AE AF Ackermann, RT Carroll, AE TI Support for national health insurance among US physicians: A national survey SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CARE REFORM; ATTITUDES; VIEWS AB Background: Nearly 40 million persons in the United States were without health insurance for all of 2000. National health insurance would remedy this situation, and many believe the success of reform efforts in this direction may depend on physician support. Objective: To determine the general attitudes of U.S. physicians toward the financing of national health care. Design: Cross-sectional study. Setting: National mailed survey. Participants: 3188 randomly sampled physicians from the American Medical Association Physician Masterfile. Measurements: Physicians were asked whether they support or oppose 1) governmental legislation to establish national health insurance and 2) a national health insurance plan in which all health care is paid for by the federal government. Weighted multivariate logistic regression analyses were performed to identify factors that independently predicted support for each of these strategies. Results: Sixty percent of eligible participants returned a survey. Forty-nine percent of physicians supported governmental legislation to establish national health insurance, and 40% opposed it. Only 26% of all physicians supported a national health insurance plan in which all health care is paid for by the federal government. In analyses adjusting for differences in personal and practice characteristics, physicians in a primary care specialty, physicians reporting that at least 20% of their patients had Medicaid, and physicians practicing in a nonprivate setting or in an inner-city location were statistically significantly more likely to support governmental legislation to establish national health insurance. Conclusions: A plurality of U.S. physicians supports governmental legislation to establish national health insurance. This support may be relevant to the success of future efforts to reform national health care. C1 Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Carroll, AE (reprint author), Indiana Univ, Sch Med, 699 W Dr,Riley Res,Room 330, Indianapolis, IN 46202 USA. NR 15 TC 8 Z9 8 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 18 PY 2003 VL 139 IS 10 BP 795 EP 801 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 744ZV UT WOS:000186663500001 PM 14623616 ER PT J AU El-Serag, H Davila, JA Petersen, NJ McGlynn, KA AF El-Serag, H Davila, JA Petersen, NJ McGlynn, KA TI The continuing increase in the incidence of hepatocellular carcinoma in the United States: An update SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HEPATITIS-C-VIRUS; PRIMARY LIVER-CANCER; DIABETES-MELLITUS; RISING INCIDENCE; RISK-FACTORS; PREVALENCE; INFECTION; JAPAN AB Background: The incidence of hepatocellular carcinoma was reported to be increasing in the United States. However, alternate explanations were diagnostic or reclassification bias and changes in the demographic features of the general population. Objective: To examine the temporal trends in the incidence of hepatocellular carcinoma. Design: Retrospective cohort study. Setting: Information collected by population-based registries of the Surveillance, Epidemiology, and End Results (SEER) program. Patients: Persons given a diagnosis of hepatocellular carcinoma between 1975 and 1998. Measurements: Linear Poisson multivariate regression model, controlling for differences in age, sex, race or ethnicity, and geographic region among patients with hepatocellular carcinoma and in the underlying population. Results: The overall age-adjusted incidence rates of hepatocellular carcinoma increased from 1.4 per 100 000 in 1975 to 1977 to 3.0 per 100 000 in 1996 to 1998. There was a 25% increase during the last 3 years of the study compared with the preceding 3 years (1993 to 1995). The increase affected most age groups above 40 years, with the greatest increase in the 45- to 49-year-old age group. White men had the greatest increase (31%) in the last time period (1996 to 1998) compared with 1993 to 1995. The Poisson regression model confirmed an almost 2-fold increase in the incidence rate ratio for hepatocellular carcinoma between 1975 to 1978 and 1996 to 1998. Conclusions: The incidence of hepatocellular carcinoma continues to increase rapidly in the United States, with rates increasing the fastest in white men 45 to 54 years of age. These findings are consistent with a true increase and could be explained by consequences of hepatitis C virus acquired during the 1960s and 1970s. C1 Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP El-Serag, H (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 19 TC 611 Z9 632 U1 2 U2 19 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 NOV 18 PY 2003 VL 139 IS 10 BP 817 EP 823 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 744ZV UT WOS:000186663500005 PM 14623619 ER PT J AU Mandelblatt, J Saha, S Teutsch, S Hoerger, T Siu, AL Atkins, D Klein, J Helfand, M AF Mandelblatt, J Saha, S Teutsch, S Hoerger, T Siu, AL Atkins, D Klein, J Helfand, M CA Cost Work Grp US Preventive Serv TI The cost-effectiveness of screening mammography beyond age 65 years: A systematic review for the US Preventive Services Task Force SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BREAST-CANCER PATIENTS; OLDER WOMEN; LIFE-EXPECTANCY; ELDERLY-WOMEN; PATTERNS; SURVIVAL; MODEL; INTERVENTIONS; COMORBIDITY; DIAGNOSIS AB Purpose: There are few data on the effects of disease biology and competing mortality on the effectiveness of screening women for breast cancer after age 65 years. The authors performed a review to determine the costs and benefits of mammography screening after age 65 years. Data Sources: Cost-effectiveness articles published between January 1989 and March 2002. Study Selection: Studies were identified by using MEDLINE and the National Health Service Economic Evaluation Database. The authors included research on screening after age 65 years conducted from a societal or government perspective; reviews and analyses of other technologies were excluded. Data Synthesis: 115 studies were identified and 10 met inclusion criteria. One study modeled age-dependent assumptions of disease biology. No study fully captured the potential harms of screening, including anxiety associated with false-positive results, overdiagnosis, and previous knowledge of cancer or living longer with the consequences of treatment. Studies differed in the specific strategies compared and in analytic approaches. On average, extending biennial screening to age 75 or 80 years was estimated to cost $34 000 to $88 000 (2002 U.S. dollars) per life-year gained, compared with stopping screening at age 65 years. Two studies suggested that it was more cost-effective to target healthy women than those with several competing risks for death. Conclusions: Current estimates suggest that biennial breast cancer screening after age 65 years reduces mortality at reasonable costs for women without clinically significant comorbid conditions. More data are needed on disease biology and preferences for benefits and harms in older women. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Merck & Co Inc, W Point, PA USA. Univ N Carolina, Res Triangle Inst, Res Triangle Pk, NC USA. Mt Sinai Sch Med, New York, NY USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Univ Rochester, Rochester, NY USA. RP Mandelblatt, J (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, 2233 Wisconsin Ave,Suite 317, Washington, DC 20007 USA. FU NCI NIH HHS [KO5 CA96940, U01CA88283]; PHS HHS [290-97-0011, 290-97-0018] NR 44 TC 76 Z9 76 U1 2 U2 5 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 NOV 18 PY 2003 VL 139 IS 10 BP 835 EP 842 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 744ZV UT WOS:000186663500007 PM 14623621 ER PT J AU Baldwin, RM Fu, X Kula, NS Baldessarini, RJ Amici, L Innis, RB Tamagnan, GD AF Baldwin, RM Fu, X Kula, NS Baldessarini, RJ Amici, L Innis, RB Tamagnan, GD TI Synthesis and affinity of a possible byproduct electrophilic radiolabeling of [I-123]IBZM SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article AB The iodobenzamide neuroleptic analogue (S)-N-(1-ethylpyrrolidin-2-ylmethyl)-2-hydroxy-5-iodo-6-methoxybenzamide (5-IBZM) was synthesized stereospecifically and its pharmacological properties were compared with the 3-iodo isomer (IBZM) used for imaging D-2 receptors in vivo. The isomer 5-IBZM had 100-fold lower affinity than IBZM and migrated with similar retention time as the byproduct formed during electrophilic iodination of BZM. (C) 2003 Elsevier Ltd. All rights reserved. C1 Yale Univ, Dept Psychiat, West Haven, CT 06516 USA. HCS, VA CT, West Haven, CT 06516 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Program Neurosci, Belmont, MA 02478 USA. Massachusetts Gen Hosp, McLean Div, McLean Res Ctr, Psychiat Res Labs, Belmont, MA 02478 USA. RP Tamagnan, GD (reprint author), Yale Univ, Dept Psychiat, West Haven, CT 06516 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 17 PY 2003 VL 13 IS 22 BP 4015 EP 4017 DI 10.1016/j.bmcl.2003.08.063 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 741XV UT WOS:000186486400028 PM 14592497 ER PT J AU Turley, S Poirot, L Hattori, M Benoist, C Mathis, D AF Turley, S Poirot, L Hattori, M Benoist, C Mathis, D TI Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE autoimmune response; pancreas; PLN; antigen transport; apoptosis ID GLUTAMIC-ACID DECARBOXYLASE; PANCREATIC LYMPH-NODES; IN-VIVO; IMMUNE-RESPONSE; NEONATAL-RAT; MOUSE MODEL; APOPTOSIS; MICE; PROGRESSION; TOLERANCE AB The prelude to type-1 diabetes is leukocyte infiltration into the pancreatic islets, or insulitis. This process begins in pancreatic lymph nodes when T lymphocytes reactive to islet beta cells encounter antigen-presenting cells (APCs) displaying peptides derived from beta cell proteins. We show here that a ripple of physiological beta cell death, which occurs at 2 wk of age in all mouse strains, precipitates the arrival of such APCs, and that the relevant APC is a dendritic cell of CD11c(+)CD11b(+)CD8alpha(-) phenotype. These findings have significant implications concerning the nature of the diabetes-provoking deficits in NOD mice, the identity of the primordial diabetogenic antigens, and our understanding of the balance between immunity and tolerance in a pathological context. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02215 USA. RP Mathis, D (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK059658, P30 DK036836, P30DK36836-16, R01DK59658-02] NR 53 TC 224 Z9 226 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 17 PY 2003 VL 198 IS 10 BP 1527 EP 1537 DI 10.1084/jem.20030966 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 748CX UT WOS:000186845600008 PM 14623908 ER PT J AU Fujikawa, K Miletic, AV Alt, FW Faccio, R Brown, T Hoog, J Fredericks, J Nishi, S Mildiner, S Moores, SL Brugge, J Rosen, FS Swat, W AF Fujikawa, K Miletic, AV Alt, FW Faccio, R Brown, T Hoog, J Fredericks, J Nishi, S Mildiner, S Moores, SL Brugge, J Rosen, FS Swat, W TI Vav1/2/3-null mice define an essential role for Vav family proteins in lymphocyte development and activation but a differential requirement in MAPK signaling in T and B cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE thymocyte; antigen receptor; signal transduction; Ca++; mitogen-activated protein kinase ID EXCHANGE FACTOR VAV; NF-KAPPA-B; ANTIGEN RECEPTOR; TYROSINE PHOSPHORYLATION; ALLELIC EXCLUSION; ADAPTER PROTEINS; DEFICIENT MICE; PROTOONCOGENE; TRANSDUCTION; THYMOCYTES AB The Vav family of Rho guanine nucleotide exchange factors is thought to orchestrate signaling events downstream of lymphocyte antigen receptors. Elucidation of Vav function has been obscured thus far by the expression of three highly related family members. We generated mice lacking all Vav family proteins and show that Vav-null mice produce no functional T or B cells and completely fall to mount both T-dependent and T-independent humoral responses. Whereas T cell development is blocked at an early stage in the thymus, immature B lineage cells accumulate in the periphery but arrest at a late "transitional" stage. Mechanistically, we show that the Vav family is crucial for both TCR and B cell receptor (BCR)-induced Ca2+ signaling and, surprisingly, is only required for mitogen-activated protein kinase (MAPK) activation in developing and mature T cells but not in B cells. Thus, the abundance of immature B cells generated in Vav-null mice may be due to intact Ras/MAPK signaling in this lineage. Although the expression of Vav1 alone is sufficient for normal lymphocyte development, our data also reveal lineage-specific roles for Vav2 and Vav3, with the first demonstration that Vav3 plays a critical compensatory function in T cells. Together, we define an essential role for the entire Vav protein family in lymphocyte development and activation and establish the limits of functional redundancy both within this family and between Vav and other Rho-guanine nucleotide exchange factors. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Siteman Canc Ctr, St Louis, MO 63110 USA. Hokkaido Univ, Grad Sch Med, Dept Biochem, Sapporo, Hokkaido 0608638, Japan. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Swat, W (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA. FU NCI NIH HHS [CA78773, R01 CA078773]; NHLBI NIH HHS [HL059561, P01 HL059561] NR 43 TC 158 Z9 164 U1 1 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 NOV 17 PY 2003 VL 198 IS 10 BP 1595 EP 1608 DI 10.1084/jem.20030874 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 748CX UT WOS:000186845600014 PM 14623913 ER PT J AU Walensky, LD Escher, I Malia, TJ Wagner, G Verdine, GL Korsmeyer, SJ AF Walensky, LD Escher, I Malia, TJ Wagner, G Verdine, GL Korsmeyer, SJ TI Novel chemically-stabilized helices of the BCL-2 family induce apoptosis of leukemia cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Hematol, Boston, MA 02115 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 3 BP 5A EP 5A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700004 ER PT J AU Huang, SC Liu, ES Cho, HT Jagadeeswaran, R Munagala, ID Benz, EJ AF Huang, SC Liu, ES Cho, HT Jagadeeswaran, R Munagala, ID Benz, EJ TI Functional role of mitotic phosphorylation of protein 4.1R by cdc2 kinase. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Jagadeeswaran, Ramasamy/C-9987-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 11 BP 7A EP 7A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700012 ER PT J AU Mims, MP Maran, J Leal, SM Hayes, TG Ittmann, M Wheeler, T Guan, YL Prchal, JT AF Mims, MP Maran, J Leal, SM Hayes, TG Ittmann, M Wheeler, T Guan, YL Prchal, JT TI African American erythrocyte genetic polymorphisms in prostate cancer. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. Methodist Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3740 BP 10B EP 10B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100031 ER PT J AU Wang, H Tan, HM Jiang, XH Pastore, Y Yang, F Schafer, AI Prchal, JT AF Wang, H Tan, HM Jiang, XH Pastore, Y Yang, F Schafer, AI Prchal, JT TI Gain-of function mutation of human EPOR accelerates re-endothelialization and inhibits neointimal formation following carotid injury. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Texas Childrens Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 26 BP 11A EP 11A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700027 ER PT J AU Schulze, H Korpal, M Bergmeier, W Italiano, JE Wahl, SM Wagner, DD Shivdasani, RA AF Schulze, H Korpal, M Bergmeier, W Italiano, JE Wahl, SM Wagner, DD Shivdasani, RA TI SLPI is a beta 1-tubulin binding protein that is expressed in megakaryocytes and platelets. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 31 BP 12A EP 12A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700032 ER PT J AU Adams, GB Calvi, LM Martin, RP Weibrecht, KW Weber, JM Olson, DP Knight, MC Bringhurst, FR Schipani, E Divieti, P Milner, LA Kronenberg, HM Scadden, DT AF Adams, GB Calvi, LM Martin, RP Weibrecht, KW Weber, JM Olson, DP Knight, MC Bringhurst, FR Schipani, E Divieti, P Milner, LA Kronenberg, HM Scadden, DT TI Osteoblasts participate in the stem cell niche regulating stem cell numbers by Jagged1 activation of notch. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Ctr Regenerat Med & Technol, Massachusetts Gen Hosp, Boston, MA USA. Univ Rochester, Sch Med, Dept Med, Endocrine Unit, Rochester, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02115 USA. Univ Rochester, Sch Med, Dept Pediat, Ctr Human Genet & Mol Pediat Dis, Rochester, NY 14642 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 52 BP 18A EP 18A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700053 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Joseph, M Libermann, TA Singh, R Anderson, KC AF Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Joseph, M Libermann, TA Singh, R Anderson, KC TI Insulin-like growth factor-1 receptor (IGF-IR/CD221): A target for monoclonal antibody-based therapy to overcome drug resistance in multiple myeloma (MM), other hematologic malignancies and solid tumors. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Inst Med, Genom Ctr, Boston, MA 02115 USA. Immunogen Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 62 BP 20A EP 21A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700063 ER PT J AU Means, RT Fleury, TW Dallalio, GA Brunson, C AF Means, RT Fleury, TW Dallalio, GA Brunson, C TI Erythroid colony formation in sickle cell anemia patients is resistant to suppression by gamma interferon: Potential role of CD36. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3787 BP 21B EP 22B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100078 ER PT J AU Smith, P Wang, FF Wilkinson, K Shipp, M Aguiar, R AF Smith, P Wang, FF Wilkinson, K Shipp, M Aguiar, R TI The phosphodiesterase PDE4B controls cell proliferation and apoptosis in DLB-CL via the PI3K/AKT pathway: Novel opportunities for clinical intervention. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting and Exhibition of the American-Society-of-Hematology CY DEC 06-09, 2003 CL San Diego, CA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 79 BP 25A EP 26A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700080 ER PT J AU Sternberg, DW Gu, TL Tothova, Z Scheijen, B Griffin, JD Gilliland, DG AF Sternberg, DW Gu, TL Tothova, Z Scheijen, B Griffin, JD Gilliland, DG TI The FOXO3a transcription factor is a target of cell survival and proliferative signaling by the NPM-ALK fusion kinase of anaplastic large cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Scheijen, Blanca/E-3523-2016 OI Scheijen, Blanca/0000-0001-8029-9230 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 78 BP 25A EP 25A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700079 ER PT J AU Rassenti, LZ Huynh, L Toy, TL Gribben, JG Keating, MJ Rai, KR Flinn, IW Byrd, JC Kay, NE Greaves, A Weiss, A Kipps, TJ AF Rassenti, LZ Huynh, L Toy, TL Gribben, JG Keating, MJ Rai, KR Flinn, IW Byrd, JC Kay, NE Greaves, A Weiss, A Kipps, TJ TI Zap-70 is a more reliable marker of disease progression risk than immunoglobulin mutation status in chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Long Isl Jewish Med Ctr, New York, NY USA. John Hopkins Canc Ctr, Baltimore, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Mayo Clin, Rochester, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif San Diego, CLL Res Consortium, La Jolla, CA 92093 USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2003 VL 102 IS 11 MA 106 BP 34A EP 34A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700106 ER PT J AU Fonseca, R Price-Troska, T Blood, E Rajkumar, SV Oken, MM Kay, NE Kyle, RA Van Wier, SA Henderson, KJ Greipp, PR Van Ness, BG AF Fonseca, R Price-Troska, T Blood, E Rajkumar, SV Oken, MM Kay, NE Kyle, RA Van Wier, SA Henderson, KJ Greipp, PR Van Ness, BG CA ECOG Myeloma Comm TI Implications of N-ras and K-ras mutations in clinical outcome and the biology of multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Dept Internal Med, Rochester, MN USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. N Mem Canc Ctr, Robbinsdale, MN USA. Univ Minnesota, Dept Genet, Minneapolis, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 113 BP 36A EP 36A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700113 ER PT J AU Bresnick, EH Im, H Kiekhaefer, CM Grass, JA Pal, S Cantor, AB Moran, TB Orkin, SH Johnson, KD AF Bresnick, EH Im, H Kiekhaefer, CM Grass, JA Pal, S Cantor, AB Moran, TB Orkin, SH Johnson, KD TI Mechanistic analysis of GATA-1-mediated activation of the murine beta-globin genes. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3849 BP 37B EP 37B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100140 ER PT J AU Barlogie, B Kyle, R Anderson, K Greipp, P Lazarus, H Jacobson, J Rasmussen, E Cromer, J Crowley, J AF Barlogie, B Kyle, R Anderson, K Greipp, P Lazarus, H Jacobson, J Rasmussen, E Cromer, J Crowley, J TI Comparable survival in multiple myeloma (MM) with high dose therapy (HDT) employing MEL 140 mg/m(2) plus TBI 12 gy Autotransplants versus standard dose therapy with VBMCP and no benefit from interferon (IFN) maintenance: Results of intergroup trial S9321. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. Canc Res & Biostat, Seattle, WA USA. NR 0 TC 19 Z9 21 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 NOV 16 PY 2003 VL 102 IS 11 MA 135 BP 42A EP 42A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700135 ER PT J AU Demetri, GD McGuire, B Tomita, D Armstrong, S Younger, J AF Demetri, GD McGuire, B Tomita, D Armstrong, S Younger, J TI The importance of optimal filgrastim dosing to support intensive chemotherapy of cancer. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3887 BP 46B EP 46B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100178 ER PT J AU Langenau, DM Ferrando, AA Traver, D Kutok, JL Kanki, JP Zon, LI Look, AT Trede, NS AF Langenau, DM Ferrando, AA Traver, D Kutok, JL Kanki, JP Zon, LI Look, AT Trede, NS TI The zebrafish as a model for studying immune responses. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 163 BP 50A EP 50A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700163 ER PT J AU Iwasaki, H Mizuno, S Takatsu, K Akashi, K AF Iwasaki, H Mizuno, S Takatsu, K Akashi, K TI GATA-2 but not GATA-1 is the major instructive regulator for eosinophil development from granulocyte/monocyte progenitors. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Immunol, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 197 BP 59A EP 59A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700197 ER PT J AU Adams, GB Calvi, LM Martin, RP Weibrecht, KW Weber, JM Olson, DP Knight, MC Bringhurst, FR Schipani, E Divieti, P Milner, LA Kronenberg, HM Scadden, DT AF Adams, GB Calvi, LM Martin, RP Weibrecht, KW Weber, JM Olson, DP Knight, MC Bringhurst, FR Schipani, E Divieti, P Milner, LA Kronenberg, HM Scadden, DT TI Genetic or pharmacologic stimulation of osteoblasts induces hematopoietic stem cell expansion and enhances bone marrow transplant efficiency. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA USA. Univ Rochester, Sch Med, Dept Med, Endocrine Unit, Rochester, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. Univ Rochester, Sch Med, Ctr Human Genet & Mol Pediat Dis, Dept Pediat, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 206 BP 62A EP 62A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700206 ER PT J AU Palomero, T Odom, DT Ferrando, AA Young, RA Look, AT AF Palomero, T Odom, DT Ferrando, AA Young, RA Look, AT TI Genome-scale location analysis of TAL1 targets in T-Cell acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 207 BP 62A EP 62A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700207 ER PT J AU Ferrando, AA Herblot, S Palomero, T Hansen, M Trang, H Fox, EA Look, AT AF Ferrando, AA Herblot, S Palomero, T Hansen, M Trang, H Fox, EA Look, AT TI Biallelic transcriptional activation of oncogenic transcription factors in T-cell acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Clin Res Inst Montreal, Montreal, PQ, Canada. Dana Farber Canc Inst, Shannon McCormack Adv Mol Diagnost Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 211 BP 63A EP 63A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700211 ER PT J AU Sun, L Feng, SJ Durante, W Kroll, MH AF Sun, L Feng, SJ Durante, W Kroll, MH TI Role of the Pyk2-MAP kinase-cPLA(2) signaling pathway in shear-dependent platelet aggregation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3959 BP 64B EP 64B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100250 ER PT J AU De Angelo, DJ Stone, RM Bruner, RJ Caligiuri, MA Heaney, ML Nimer, SD Paquette, R Sawyers, CL Lambing, JL Lokker, NA Giese, NA Sinha, V Cooper, MR Druker, BJ Heinrich, MC AF De Angelo, DJ Stone, RM Bruner, RJ Caligiuri, MA Heaney, ML Nimer, SD Paquette, R Sawyers, CL Lambing, JL Lokker, NA Giese, NA Sinha, V Cooper, MR Druker, BJ Heinrich, MC TI Phase I clinical results with MLN518, a novel FLT3 antagonist: Tolerability, pharmacokinetics, and pharmacodynamics. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Comprehens Canc Ctr, Columbus, OH USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif Los Angeles, Ctr Med, Los Angeles, CA 90024 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Oregon Hlth Sci Univ, Portland, OR USA. RI Sawyers, Charles/G-5327-2016 NR 0 TC 10 Z9 10 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 NOV 16 PY 2003 VL 102 IS 11 MA 219 BP 65A EP 66A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700219 ER PT J AU Gilliland, DG Kelly, L Curley, DP Neuberg, D Yu, JC Lokker, N Giese, N AF Gilliland, DG Kelly, L Curley, DP Neuberg, D Yu, JC Lokker, N Giese, N TI Therapeutic efficacy of all-trans-retinoic acid (ATRA) combined with the FLT3 inhibitor MLN518 in a murine model of acute promyelocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millennium Pharmaceut, San Francisco, CA USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2003 VL 102 IS 11 MA 222 BP 66A EP 66A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700222 ER PT J AU Friedberg, JW Kim, H McCauley, M Hessel, EM Sims, P Fisher, DC Coffman, R Freedman, AS AF Friedberg, JW Kim, H McCauley, M Hessel, EM Sims, P Fisher, DC Coffman, R Freedman, AS TI Combination immunotherapy for non-Hodgkin's lymphoma (NHL) with a CpG oligonucleotide (1018 ISS) and rituximab: Biological responses through increased interferon-a/beta-inducible gene expression without significant toxicity. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. Dynavax Technol, Berkeley, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 232 BP 69A EP 69A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700232 ER PT J AU Grever, MR Dewald, GW Lucas, DM Neuberg, DS Baird, ME Paternoster, SF Brockman, SR Lozanski, G Rizouli, V Gribben, JG Flinn, IW Tallman, MS Kitada, S Reed, JC Staudt, LM Paietta, E Byrd, JC AF Grever, MR Dewald, GW Lucas, DM Neuberg, DS Baird, ME Paternoster, SF Brockman, SR Lozanski, G Rizouli, V Gribben, JG Flinn, IW Tallman, MS Kitada, S Reed, JC Staudt, LM Paietta, E Byrd, JC TI ZAP-70 protein expression varies by interphase cytogenetic group and may predict disease progression to requirement of treatment among select genetic groups in patients with chronic lymphocytic leukemia (CLL). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ohio State Univ, Columbus, OH 43210 USA. Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Burnham Inst, La Jolla, CA 92037 USA. Johns Hopkins Univ, Baltimore, MD USA. Our Lady Mercy Bronx, Bronx, NY USA. NIH, Bethesda, MD 20892 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2003 VL 102 IS 11 MA 244 BP 73A EP 73A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700244 ER PT J AU Mitsiades, CS McMullan, CJ Mitsiades, N Faircloth, G Lopez-Martin, JA Otero-Serano, G Anderson, KC AF Mitsiades, CS McMullan, CJ Mitsiades, N Faircloth, G Lopez-Martin, JA Otero-Serano, G Anderson, KC TI Pre-clinical studies in support of the clinical development of aplidin (R) (APL) for the treatment of multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. Pharma Mar SA, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 250 BP 74A EP 74A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700250 ER PT J AU Hideshima, T Chauhan, D Hayashi, T Akiyama, N Mitsiades, N Mitsiades, C Podar, K Munshi, NC Richardson, PG Anderson, KC AF Hideshima, T Chauhan, D Hayashi, T Akiyama, N Mitsiades, N Mitsiades, C Podar, K Munshi, NC Richardson, PG Anderson, KC TI Blockade of IL-6 triggered signaling cascades by PS-341 (Velcade (R)) via Caspase-dependent downregulation of gp130 in multiple myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 253 BP 75A EP 75A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700253 ER PT J AU Alyea, EP Kim, HT Cutler, C Ho, V Lee, SJ Parik, B Windawi, S DeAngelo, D Stone, RM Ritz, J Antin, JH Soiffer, RJ AF Alyea, EP Kim, HT Cutler, C Ho, V Lee, SJ Parik, B Windawi, S DeAngelo, D Stone, RM Ritz, J Antin, JH Soiffer, RJ TI AML and MDS treated with nonmyeloablative stem cell transplantation: Overall and progression free survival comparable to myeloablative transplantation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2003 VL 102 IS 11 MA 266 BP 79A EP 79A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700266 ER PT J AU Joffe, S Mello, M Lee, S AF Joffe, S Mello, M Lee, S TI Advance care planning among patients undergoing hematopoietic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 272 BP 81A EP 81A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700272 ER PT J AU Hirano, N Butler, MO Freeman, GJ Nadler, LM AF Hirano, N Butler, MO Freeman, GJ Nadler, LM TI CD83 : CD83L engagement plays an important role in the stimulation and expansion of antigen specific naive and memory CD8+T cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 286 BP 84A EP 85A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700286 ER PT J AU Lafuente, EM Krause, M Constantine, EM Berezovskaya, A Nadler, LM Boussiotis, VA AF Lafuente, EM Krause, M Constantine, EM Berezovskaya, A Nadler, LM Boussiotis, VA TI RIAM, a novel rap1-interacting adaptor molecule links TCR-mediated signals to the actin cytoskeleton and regulates organization of the lipid rafts. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA USA. RI Lafuente, Esther M/K-5684-2014 OI Lafuente, Esther M/0000-0001-8466-1022 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 285 BP 84A EP 84A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700285 ER PT J AU Hirano, N Butler, MO Nadler, LM AF Hirano, N Butler, MO Nadler, LM TI IL15, but not IL2, enables naive CD8(+) T cells to acquire the ability to secrete IFN-gamma in an antigen specific manner. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 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 AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 288 BP 85A EP 85A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700288 ER PT J AU Bussel, JB George, JN Kuter, DJ Wasser, JS Aledort, LM Chen, MG Nichol, JL AF Bussel, JB George, JN Kuter, DJ Wasser, JS Aledort, LM Chen, MG Nichol, JL TI An open-label, dose-finding study evaluating the safety and platelet response of a novel thrombopoietic protein (AMG 531) in thrombocytopenic adult patients with immune thrombocytopenic purpura (ITP). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Cornell Univ, Weill Med Coll, Div Pediat Hematol Oncol, New York, NY USA. Univ Oklahoma, Htlh Sci Ctr, Oklahoma City, OK USA. Mass Gen Hosp, Hematol Unit, Boston, MA USA. DeQualtro Community Canc Ctr, Manchester, CT USA. Mt Sinai Hosp, New York, NY 10029 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 10 Z9 13 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 NOV 16 PY 2003 VL 102 IS 11 MA 293 BP 86A EP 86A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700293 ER PT J AU Heinrich, MC Yee, KWH Giese, NA Schittenhelm, M AF Heinrich, MC Yee, KWH Giese, NA Schittenhelm, M TI MLN518, a potent FLT3 inhibitor, displays synergistic effects with cytarabine and daunorubicin on FLT3 ITD leukemia cell lines. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 OHSU, Inst Canc, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Millennium Pharmaceut, San Francisco, CA USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 330 BP 97A EP 97A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700330 ER PT J AU De Angelo, DJ Stone, RM Durrant, S Liu, DL Baccarani, M Schiffer, CA Amrein, P Sherman, ML AF De Angelo, DJ Stone, RM Durrant, S Liu, DL Baccarani, M Schiffer, CA Amrein, P Sherman, ML TI Gemtuzumab ozogamicin (Mylotarg (R)) in combination with induction chemotherapy for the treatment of patients with de novo acute myeloid leukemia: Two age-specific phase 2 trials. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Queensland, Royal Brisbane Hosp, Herston, Qld, Australia. New York Med Coll, Valhalla, NY 10595 USA. Osped S Orsola Malpighi, Bologna, Italy. Wayne State Univ, Sch Med, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Wyeth Ayerst Res, Cambridge, MA USA. NR 0 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 341 BP 100A EP 100A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700341 ER PT J AU Gilliland, DG Lee, BH Williams, IR Boulton, CL Anastasiadou, E Wojiski, S Amaral, SM Curley, DP Duclos, N Huntly, B Griffin, JD AF Gilliland, DG Lee, BH Williams, IR Boulton, CL Anastasiadou, E Wojiski, S Amaral, SM Curley, DP Duclos, N Huntly, B Griffin, JD TI FLT3 internal tandem duplication mutations induce myeloproliferative or lymphoid disease in a transgenic mouse model that responds to the FLT3 inhibitor PKC412. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Emory Univ, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 363 BP 107A EP 107A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700363 ER PT J AU Wilkinson, K Velloso, E Lopes, L Lee, C Aster, J Shipp, M Aguiar, RC AF Wilkinson, K Velloso, E Lopes, L Lee, C Aster, J Shipp, M Aguiar, RC TI Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: Involvement of PDGFRB and response to imatinib. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Sao Paulo, Div Hematol, Sao Paulo, Brazil. Hosp AC Camargo Fund Antonio Prudente, Dept Pediat, Sao Paulo, Brazil. RI Velloso, Elvira/K-7634-2013 NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 368 BP 108A EP 109A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700368 ER PT J AU O'Brien, SM Gribben, JG Thomas, DA Albitar, M Wierda, W Ferrajoli, A Lerner, S Kantarjian, HM Kipps, T Keating, MJ AF O'Brien, SM Gribben, JG Thomas, DA Albitar, M Wierda, W Ferrajoli, A Lerner, S Kantarjian, HM Kipps, T Keating, MJ CA CLL Res Consortium TI Alemtuzumab for minimal residual disease in CLL. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 7 Z9 7 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 NOV 16 PY 2003 VL 102 IS 11 MA 371 BP 109A EP 109A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700371 ER PT J AU Tai, YT Podar, K Catley, L Tseng, YH Shringarpure, R Burger, R Akiyama, M Hideshima, T Chauhan, D Mitsiades, N Richardson, P Munshi, NC Kahn, CR Mitsiades, C Anderson, KC AF Tai, YT Podar, K Catley, L Tseng, YH Shringarpure, R Burger, R Akiyama, M Hideshima, T Chauhan, D Mitsiades, N Richardson, P Munshi, NC Kahn, CR Mitsiades, C Anderson, KC TI Insulin-like growth factor-1 induces adhesion and migration in human multiple myeloma cells via activation of b1-integrin and phosphatidylinositol 3-kinase/AKT signaling beta. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 378 BP 111A EP 111A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700378 ER PT J AU Brown, JR Yeckes, H Friedberg, JW Neuberg, D Kim, H Nadler, LM Freedman, AS AF Brown, JR Yeckes, H Friedberg, JW Neuberg, D Kim, H Nadler, LM Freedman, AS TI Incidence of solid tumors and myelodysplasia after autologous bone marrow transplantation for non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 398 BP 117A EP 117A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700401 ER PT J AU Grabowski, EF Rabinov, JD Grant, PE Jones, RM Butler, WE Buonanno, FS AF Grabowski, EF Rabinov, JD Grant, PE Jones, RM Butler, WE Buonanno, FS TI Management of massive sinus thrombosis in a 6-year-old girl by a pediatric stroke team. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4228 BP 130B EP 131B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100519 ER PT J AU Hock, H Meade, E Medeiros, S Schindler, R Valk, PJM Fujiwara, Y Orkin, SH AF Hock, H Meade, E Medeiros, S Schindler, R Valk, PJM Fujiwara, Y Orkin, SH TI TEL/ETV6 controls maintenance of hematopoietic stem cells (HSCs) and megakaryocyte development. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 447 BP 131A EP 131A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700447 ER PT J AU Li, AH Armstrong, S Rue, M Wang, HJ Zhou, JB Silverman, LB Sallan, SE Gribben, JG AF Li, AH Armstrong, S Rue, M Wang, HJ Zhou, JB Silverman, LB Sallan, SE Gribben, JG TI V-H gene usage, incomplete DJ(H) recombinations and MLL rearrangements in infant with B-lineage acute lymphoblastic leukemia: Implications for leukemic transformation occurring at an earlier stage of B cell development. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,DFCI ALL Consortium, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 482 BP 140A EP 140A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700482 ER PT J AU De Angelo, DJ Soiffer, RJ Galinisky, I Clark, JJ Gilliland, DG Shanahan, J Amrein, PC Stone, RM AF De Angelo, DJ Soiffer, RJ Galinisky, I Clark, JJ Gilliland, DG Shanahan, J Amrein, PC Stone, RM TI Imatinib mesylate (Gleevec (R)) for patients with chronic idiopathic myelofibrosis (CIM): A phase II trial SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 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 NOV 16 PY 2003 VL 102 IS 11 MA 502 BP 146A EP 146A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700502 ER PT J AU Gertz, MA Rue, M Blood, E Kaminer, LS Vesole, DH Greipp, PR AF Gertz, MA Rue, M Blood, E Kaminer, LS Vesole, DH Greipp, PR TI Rituximab for Waldenstrom's macroglobulinemia (WM) (E3A98): An ECOG phase II pilot study for untreated or previously treated patients. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Northwestern Univ, Evanston Hosp, Dept Hematol, Evanston, IL 60201 USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2003 VL 102 IS 11 MA 508 BP 148A EP 148A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700508 ER PT J AU Richardson, PG Briemberg, H Jagannath, S Barlogie, B Berenson, J Singhal, S Traynor, A Siegel, D Irwin, D Schuster, M Srkalovic, G Alexanian, R Rajkumar, SV Limentani, S Alsina, M Orlowski, R Kuter, D Esseltine, D Adams, J Schenkein, DP Wen, P Amato, A Anderson, KC AF Richardson, PG Briemberg, H Jagannath, S Barlogie, B Berenson, J Singhal, S Traynor, A Siegel, D Irwin, D Schuster, M Srkalovic, G Alexanian, R Rajkumar, SV Limentani, S Alsina, M Orlowski, R Kuter, D Esseltine, D Adams, J Schenkein, DP Wen, P Amato, A Anderson, KC TI Peripheral neuropathy following bortezomib (VELCADE (TM), formerly PS-341) therapy in patients with advanced multiple myeloma (MM): Characterization and reversibility. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincents Comp Can Cen, New York, NY USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Robert H Lurie Can Cen, Chicago, IL USA. Carol G Simon Can Cen, Morristown, NJ USA. Alta Bates Comp Can Cen, Berkeley, CA USA. NY Presby Hosp, New York, NY USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Carolinas Hem Onc Assoc, Charlotte, NC USA. H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. Univ N Carolina, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Millennium Pharm Inc, Cambridge, MA USA. NR 0 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 512 BP 149A EP 149A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700512 ER PT J AU Eom, HS Rubio, MT Bronson, RT Sykes, M AF Eom, HS Rubio, MT Bronson, RT Sykes, M TI The role of alpha(1,3)Fucosyltranferases Fuc-TIV and Fuc-TVII in inducing GVHD. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Dana Faber Canc Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 516 BP 150A EP 150A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700516 ER PT J AU Miklos, DB Kim, HT Lee, SJ Miller, KH Guo, LX Hochberg, EP Wu, CJ Alyea, EP Cutler, C He, VT Soiffer, RJ Antin, JH Ritz, J AF Miklos, DB Kim, HT Lee, SJ Miller, KH Guo, LX Hochberg, EP Wu, CJ Alyea, EP Cutler, C He, VT Soiffer, RJ Antin, JH Ritz, J TI Antibody response to H-Y minor histocompatibility proteins correlates with chronic graft versus host disease and disease remission. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 519 BP 151A EP 151A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700519 ER PT J AU Wingert, RA Brownlie, A Dooley, K Fraenkel, P Axe, J Zon, LI AF Wingert, RA Brownlie, A Dooley, K Fraenkel, P Axe, J Zon, LI TI Gene duplication in zebrafish provides a model for erythroid-specific disruption of the TfR1 gene. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 541 BP 157A EP 157A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700541 ER PT J AU Alcantara, O Guo, Y Boldt, DH AF Alcantara, O Guo, Y Boldt, DH TI Iron availability influences binding of multiple transcription factors to the p21(WAF1/CIP1) gene promoter during myelopoiesis. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4345 BP 159B EP 159B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100636 ER PT J AU Shimamura, A Leary, RJ Thornley, I MacKeigan, S AF Shimamura, A Leary, RJ Thornley, I MacKeigan, S TI Variable SBDS protein expression in Shwachman-Diamond patients: Implications for pathogenesis. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 551 BP 159A EP 159A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700551 ER PT J AU Wang, XZ Andreassen, P D'Andrea, AD AF Wang, XZ Andreassen, P D'Andrea, AD TI Functional interaction of the Fanconi Anemia protein, FANCD2 with the breast cancer susceptibility protein, BRCA2, in damage chromatin. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 549 BP 159A EP 159A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700549 ER PT J AU Maran, J Jedlickova, K Stockton, D Prchal, JT AF Maran, J Jedlickova, K Stockton, D Prchal, JT TI Finding the novel molecular defect in a family with high erythropoietin autosomal dominant polycythemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 2 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 NOV 16 PY 2003 VL 102 IS 11 MA 4359 BP 162B EP 162B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100650 ER PT J AU Demetri, GD Dale, DC Aapro, MS Woodman, RC AF Demetri, GD Dale, DC Aapro, MS Woodman, RC TI Epoetin alfa improves hemoglobin and quality of life in anemic geriatric cancer patients >= 60 years receiving chemotherapy. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Univ Washington, Div Internal Med, Seattle, WA 98195 USA. Clin Genolier, Inst Multidisciplinary Oncol, Genolier, Switzerland. Ortho Biotech Prod, LP, Clin Affairs, Bridgewater, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4368 BP 164B EP 165B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100659 ER PT J AU Davidson, AJ Ernst, P Wang, Y Dekens, MPS Kingsley, PD Palis, J Korsmeyer, SJ Daley, GQ Zon, LI AF Davidson, AJ Ernst, P Wang, Y Dekens, MPS Kingsley, PD Palis, J Korsmeyer, SJ Daley, GQ Zon, LI TI Caudal-like genes act upstream of hox genes to induce hematopoietic progenitors in zebrafish and mouse embryonic stem cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting and Exhibition of the American-Society-of-Hematology CY DEC 06-09, 2003 CL San Diego, CA SP Amer Soc Hematol C1 Univ Rochester, Ctr Human Genet & Mol Pediat Dis, Dept Pediat, Rochester, NY USA. Max Planck Inst Entwicklungsbiol, Dept Genet, D-72076 Tubingen, Germany. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst,Div Hematol Oncol, Dana Farber Canc Inst,Childrens Hosp,Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 577 BP 166A EP 166A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700577 ER PT J AU Sarmento, LM Classon, M Limon, A Tavares, MJ Cardoso, AA Scadden, DT Carlesso, N AF Sarmento, LM Classon, M Limon, A Tavares, MJ Cardoso, AA Scadden, DT Carlesso, N TI Notch1 induces Skp2 transcription and P27(Kip1) degradation during cell cycle progression. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Sci Res Lab Inc, Somerville, MA USA. Inst Mol Med, Unit Tumor Biol, Lisbon, Portugal. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 585 BP 168A EP 168A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700585 ER PT J AU Means, RT Fleury, T Dallalio, G Bielawski, J AF Means, RT Fleury, T Dallalio, G Bielawski, J TI Role of sphingosine in cell death induced by erythropoietin withdrawal. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4398 BP 172B EP 172B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100689 ER PT J AU Harousseau, JL Reiffers, J Lowenberg, B Thomas, X Huguet, F Fenaux, P Stone, RM Lancet, J Arani, R Rackoff, W Thibault, A AF Harousseau, JL Reiffers, J Lowenberg, B Thomas, X Huguet, F Fenaux, P Stone, RM Lancet, J Arani, R Rackoff, W Thibault, A TI Zarnestra (TM) (R115777) in patients with relapsed and refractory acute myelogenous leukemia (AML): Results of a multicenter phase 2 study. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Johnson & Johnson Pharmaceut Res & Dev LLC, Titusville, NJ USA. Univ Rochester, Rochester, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hop Claude Huriez, Lille, France. CHU, Serv Hematol, Toulouse, France. Hop Edouard Herriot, Lyon, France. Erasmus Univ, Rotterdam, Netherlands. Hop Haut Leveque, Pessac, France. Hop Hotel Dieu, Nantes, France. NR 0 TC 13 Z9 13 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 NOV 16 PY 2003 VL 102 IS 11 MA 614 BP 176A EP 176A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700614 ER PT J AU Savage, KJ Monti, S Kutok, J Cattoretti, G Neuberg, D Laval, L Kurtin, P Del Chin, P Ladd, C Feuerhake, F Aguiar, R Li, SG Salles, G Berger, F Jing, W Pinkus, GS Habermann, T Dalla-Favera, R Harris, NL Aster, JC Golub, TR Shipp, MA AF Savage, KJ Monti, S Kutok, J Cattoretti, G Neuberg, D Laval, L Kurtin, P Del Chin, P Ladd, C Feuerhake, F Aguiar, R Li, SG Salles, G Berger, F Jing, W Pinkus, GS Habermann, T Dalla-Favera, R Harris, NL Aster, JC Golub, TR Shipp, MA TI The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Ctr Genome Res, Cambridge, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Columbia Univ, Inst Canc Genet, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Ctr Hosp Lyon Sud, Lyon, France. Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Dept Med, Rochester, MN USA. NR 0 TC 10 Z9 11 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 NOV 16 PY 2003 VL 102 IS 11 MA 622 BP 179A EP 179A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700622 ER PT J AU Shringarpure, R Chauhan, D Burger, R Catley, L Tai, YT Podar, K Hideshima, T Mitsiades, N Mitsiades, C Anderson, KC AF Shringarpure, R Chauhan, D Burger, R Catley, L Tai, YT Podar, K Hideshima, T Mitsiades, N Mitsiades, C Anderson, KC TI Gene expression analysis of tumor cells sensitive and resistant to PS-341 (Bortezomib) treatment: Clinical implications. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 629 BP 180A EP 181A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700629 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Treon, SP Richardson, PG Munshi, NC Joseph, M Libermann, TA Anderson, KC AF Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Treon, SP Richardson, PG Munshi, NC Joseph, M Libermann, TA Anderson, KC TI The proteasome inhibitor bortezomib (PS-341) is active against Waldenstrom's macroglobulinemia (WM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. NR 0 TC 5 Z9 6 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 NOV 16 PY 2003 VL 102 IS 11 MA 631 BP 181A EP 181A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700631 ER PT J AU Drandi, D Lee, C Dal Cin, P Gribben, JG AF Drandi, D Lee, C Dal Cin, P Gribben, JG TI Array-based comparative genomic hybridization identifies deletion at 14q32 as a new prognostic marker in chronic lymphocytic leukemia (CLL). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RI drandi, daniela/Q-6504-2016 NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 649 BP 186A EP 186A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700649 ER PT J AU Chauhan, D Li, GL Podar, K Hideshima, T Nicholas, M Constatntine, M Catley, L Munshi, N Anderson, KC AF Chauhan, D Li, GL Podar, K Hideshima, T Nicholas, M Constatntine, M Catley, L Munshi, N Anderson, KC TI Targeting mitochondria to overcome conventional and Bortezomib-resistance in multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 2 Z9 2 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 NOV 16 PY 2003 VL 102 IS 11 MA 658 BP 189A EP 189A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700658 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Hideshima, T Chauhan, D Munshi, NC Joseph, M Libermann, TA Anderson, KC AF Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Hideshima, T Chauhan, D Munshi, NC Joseph, M Libermann, TA Anderson, KC TI Molecular profiles of sensitivity or resistance of multiple myeloma (MM) cells to conventional and novel anti-myeloma agents: Clinical implications for rationale design of strategies to overcome drug-resistance in MM. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Inst Med, Genom Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 659 BP 189A EP 189A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700659 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Akiyama, M Chauhan, D Munshi, NC Joseph, M Libermann, TA Richon, VM Marks, PA Anderson, KC AF Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Akiyama, M Chauhan, D Munshi, NC Joseph, M Libermann, TA Richon, VM Marks, PA Anderson, KC TI Molecular profile of the anti-myeloma activity of histone deacetylase (HDAC) inhibitors: Biological and therapeutic implications. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Inst Med, Genom Ctr, Boston, MA 02115 USA. Aton Pharma Inc, Tarrytown, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 657 BP 189A EP 189A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700657 ER PT J AU Bellucci, R Wu, CJ Chiaretti, S Alyea, EP Munshi, NC Anderson, KC Dranoff, G Ritz, J AF Bellucci, R Wu, CJ Chiaretti, S Alyea, EP Munshi, NC Anderson, KC Dranoff, G Ritz, J TI Complete response to donor lymphocyte infusion in patients with multiple myeloma is associated with antibody response to BCMA, a plasma cell membrane receptor. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 671 BP 192A EP 193A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700671 ER PT J AU Foley, JE Jung, U Mierra, A Eckhaus, M Bierer, BE Fowler, DH AF Foley, JE Jung, U Mierra, A Eckhaus, M Bierer, BE Fowler, DH TI Ex vivo rapamycin generates CD4(+) Th2 cells that potently abrogate murine GVHD. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 668 BP 192A EP 192A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700668 ER PT J AU Richardson, P Soiffer, RJ Antin, JH Jin, Z Vredenburgh, JJ Kurtzberg, J Martin, PL Hockenbery, D Steinbach, G Murray, KF Vogelsang, GB Chen, A Krishnan, A Prasad, VK Warren, DL Momtaz, P Batchelder, A Wei, LJ Rifai, N Bradwin, G Iacobelli, M McDonald, GB Guinan, EC AF Richardson, P Soiffer, RJ Antin, JH Jin, Z Vredenburgh, JJ Kurtzberg, J Martin, PL Hockenbery, D Steinbach, G Murray, KF Vogelsang, GB Chen, A Krishnan, A Prasad, VK Warren, DL Momtaz, P Batchelder, A Wei, LJ Rifai, N Bradwin, G Iacobelli, M McDonald, GB Guinan, EC TI Defibrotide (DF) is effective in the treatment of severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post stem cell transplantation (SCT): Results of a phase II, multicenter, randomized study. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Columbia Univ, New York, NY 10027 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. City Hope Canc Ctr, Duarte, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Gentium SpA, Como, Italy. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 674 BP 193A EP 193A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700674 ER PT J AU Zorn, E Miklos, DB Floyd, B Soiffer, RJ Antin, JH Ritz, J AF Zorn, E Miklos, DB Floyd, B Soiffer, RJ Antin, JH Ritz, J TI Distinct peptide specificities of coordinated T and B cell immune response to DBY minor histocompatibility antigen following allogeneic stem cell transplantation SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 672 BP 193A EP 193A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700672 ER PT J AU Schittenhelm, M Yee, KWH Braziel, R Bainbridge, T O'Farrell, AM Cherrington, J Schroeder, A Town, A McGreevey, L Heinrich, MC AF Schittenhelm, M Yee, KWH Braziel, R Bainbridge, T O'Farrell, AM Cherrington, J Schroeder, A Town, A McGreevey, L Heinrich, MC TI Mutation of the FLT3 TK1 domain: A new class of activating FLT3 mutations associated with AML. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. SUGEN Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4535 BP 204B EP 204B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100826 ER PT J AU Cretien, A Da Costa, LM Rince, P Proust, A Mohandas, N Gazda, H Niemeyer, C Delaunay, J Tchernia, G AF Cretien, A Da Costa, LM Rince, P Proust, A Mohandas, N Gazda, H Niemeyer, C Delaunay, J Tchernia, G TI Subcellular localization and protein expression level of twelve ribosomal protein S19 mutants identified in DBA patients. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Hop Bicetre, INSERM U473, Le Kremlin Bicetre, France. Hop Bicetre, Hematol Lab, Le Kremlin Bicetre, France. New York Blood Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Freiburg, Kinderklin, D-7800 Freiburg, Germany. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 717 BP 205A EP 205A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700717 ER PT J AU Wang, ZY Cohen, K Shao, Y Mole, P Dombkowski, D Scadden, DT AF Wang, ZY Cohen, K Shao, Y Mole, P Dombkowski, D Scadden, DT TI Eph kinase, EphB4, regulates ES cell differentiation of mesodermal tissues. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 739 BP 211A EP 211A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700739 ER PT J AU Zhou, JB Li, AH Diller, L Gribben, JG AF Zhou, JB Li, AH Diller, L Gribben, JG TI Application of molecular markers for minimal residual disease detection in neuroblastoma using real-time PCR technology. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4582 BP 215B EP 216B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100873 ER PT J AU Silverman, LB Supko, JG Levy, DE Dalton, VK Gelber, RD Sallan, SE AF Silverman, LB Supko, JG Levy, DE Dalton, VK Gelber, RD Sallan, SE TI Individualized dosing of asparaginase in childhood acute lymphoblastic leukemia (ALL). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 786 BP 224A EP 224A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700786 ER PT J AU Stam, RW den Boer, ML Armstrong, SA Sallen, SE Kazemier, KM Pieters, R AF Stam, RW den Boer, ML Armstrong, SA Sallen, SE Kazemier, KM Pieters, R TI Targeting FLT3 in MLL gene rearranged infant Acute Lymphoblastic Leukemia (ALL). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Sophia Childrens Univ Hosp, Erasmus MC, Rotterdam, Netherlands. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 784 BP 224A EP 224A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700784 ER PT J AU Chauhan, D Li, G Shringarpure, R Podar, K Hideshima, T Anderson, KC AF Chauhan, D Li, G Shringarpure, R Podar, K Hideshima, T Anderson, KC TI Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341-resistance in lymphoma cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 794 BP 226A EP 227A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700794 ER PT J AU Sattler, M Chu, SC Gramlich, JL Pride, YB Quinnan, LA Kim, JH Chauhan, D Podar, K Salgia, R Griffin, JD AF Sattler, M Chu, SC Gramlich, JL Pride, YB Quinnan, LA Kim, JH Chauhan, D Podar, K Salgia, R Griffin, JD TI Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting and Exhibition of the American-Society-of-Hematology CY DEC 06-09, 2003 CL San Diego, CA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 804 BP 229A EP 229A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700804 ER PT J AU Mauerer, K Gorgun, G Drandi, D Gribben, JG AF Mauerer, K Gorgun, G Drandi, D Gribben, JG TI Impact of binding affinity to HLA*A0201 on both generation of cytotoxic T cells and their effector function to kill peptide pulsed APCs and CLL cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. CLL Res Consortium, Boston, MA USA. RI drandi, daniela/Q-6504-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 809 BP 230A EP 231A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700809 ER PT J AU Gorgun, G Zahrieh, D Drandi, D Neuberg, D Gribben, J AF Gorgun, G Zahrieh, D Drandi, D Neuberg, D Gribben, J TI Gene expression profiling reveals defects in genes regulating T cell diffentiation and effector pathways in T cells in patients with CLL. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. CLL Res Consortium, Boston, MA USA. RI drandi, daniela/Q-6504-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 814 BP 232A EP 232A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700814 ER PT J AU Richardson, PG Jagannath, S Schlossman, R Zeldenrust, S Rajkumar, S Alsina, M Desikan, KR Mitsiades, CS Kelly, K Doss, D McKenney, M Gorelik, S Warren, D Freeman, A Rich, R Knight, R Olesnyckyj, M Patin, J Zeldis, J Dalton, W Anderson, KC AF Richardson, PG Jagannath, S Schlossman, R Zeldenrust, S Rajkumar, S Alsina, M Desikan, KR Mitsiades, CS Kelly, K Doss, D McKenney, M Gorelik, S Warren, D Freeman, A Rich, R Knight, R Olesnyckyj, M Patin, J Zeldis, J Dalton, W Anderson, KC TI A multi-center, randomized, phase 2 study to evaluate the efficacy and safety of 2 CDC-5013 dose regimens when used alone or in combination with dexamethasone (Dex) for the treatment of relapsed or refractory multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Mayo Clin, Rochester, MN USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Celgene Corp, Warren, NJ USA. NR 0 TC 24 Z9 25 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 825 BP 235A EP 235A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700825 ER PT J AU Jagannath, S Barlogie, B Berenson, J Singhal, S Alexanian, R Srkalovic, G Orlowski, R Richardson, PG Nix, D Guerciolini, R Esseltine, D Anderson, KC AF Jagannath, S Barlogie, B Berenson, J Singhal, S Alexanian, R Srkalovic, G Orlowski, R Richardson, PG Nix, D Guerciolini, R Esseltine, D Anderson, KC TI Limited experience from 2 phase 2 trials suggests bortezomib can be given safely in multiple myeloma (MM) patients (pts) with severe renal impairment with comparable responses and toxicities. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 St Vincents Comp Can Cen, New York, NY USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Robert H Lurie Can Cen, Chicago, IL USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millennium Pharm, Cambridge, MA USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2003 VL 102 IS 11 MA 828 BP 236A EP 236A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700828 ER PT J AU Mielcarek, M Gooley, T Martin, PJ Chauncey, TR Young, BA Storb, R Torok-Storb, B AF Mielcarek, M Gooley, T Martin, PJ Chauncey, TR Young, BA Storb, R Torok-Storb, B TI Survival after hematopoietic cell transplantation according to ethnic background. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 841 BP 239A EP 240A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700841 ER PT J AU Panse, JP Heimfeld, S Guthrie, KA Maris, M Maloney, DG Baril, B Little, MT Chauncey, T Storb, R Sandmaier, BM AF Panse, JP Heimfeld, S Guthrie, KA Maris, M Maloney, DG Baril, B Little, MT Chauncey, T Storb, R Sandmaier, BM TI Allogeneic peripheral blood graft composition affects early T-cell chimerism and later clinical outcomes after nonmyeloablative conditioning. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 843 BP 240A EP 240A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700843 ER PT J AU Cutler, C Kim, H Micale, E Ho, V Alyea, E Lee, SJ Fisher, DC Hochberg, E Soiffer, RJ Antin, JH AF Cutler, C Kim, H Micale, E Ho, V Alyea, E Lee, SJ Fisher, DC Hochberg, E Soiffer, RJ Antin, JH TI Sirolimus and tacrolimus without methotrexate as graft-vs.-host disease prophylaxis after matched, related peripheral blood stem cell transplantation: Low transplant related morbidity and excellent GVHD control. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 849 BP 242A EP 242A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700849 ER PT J AU Ho, VT Zahrieh, D Hochberg, E Cutler, C Miklos, D Wu, CJ Neuberg, D Micale, E Steckel, S Fisher, DC Lee, SJ Alyea, EP Ritz, J Soiffer, RJ Antin, JH AF Ho, VT Zahrieh, D Hochberg, E Cutler, C Miklos, D Wu, CJ Neuberg, D Micale, E Steckel, S Fisher, DC Lee, SJ Alyea, EP Ritz, J Soiffer, RJ Antin, JH TI Safety and efficacy of denileukin diftitox in patients with steroid refractory graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Ligand Pharmaceut Inc, San Diego, CA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 850 BP 242A EP 242A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700850 ER PT J AU Huang, SC Liu, ES Zhou, AY Cheng, H Norton, SM Tang, TK Benz, EJ AF Huang, SC Liu, ES Zhou, AY Cheng, H Norton, SM Tang, TK Benz, EJ TI Regulation of the alternative splicing of exon 2'/2 of protein 4.1R SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 899 BP 255A EP 256A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700899 ER PT J AU Yang, G Huang, SC Benz, EJ AF Yang, G Huang, SC Benz, EJ TI Interaction of SF2/ASF and an exonic splicing enhancer regulates exon 16 splicing in protein 4.1R pre-mRNA. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 901 BP 256A EP 256A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700901 ER PT J AU Litzow, MR Lee, S Bennett, JM Gallagher, RE Paietta, EM Rousey, SR Tallman, MS AF Litzow, MR Lee, S Bennett, JM Gallagher, RE Paietta, EM Rousey, SR Tallman, MS TI A phase II trial of arsenic trioxide (AT) for relapsed and refractory acute lymphoblastic leukemia (ALL). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Mayo Clin, Div Hematol, Rochester, MN USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Rochester, Ctr Canc, Rochester, NY 14627 USA. Montefiore Med Ctr, Dept Oncol, Bronx, NY 10467 USA. Our Lady Mercy Med Ctr, Ctr Comprehens Canc, Bronx, NY 10467 USA. Metro Minnesota CCOP, St Louis Pk, MN USA. Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. Eastern Cooperat Oncol Grp, Boston, MA USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2003 VL 102 IS 11 MA 4766 BP 260B EP 260B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101057 ER PT J AU Butler, MO Hirano, N Nadler, LM AF Butler, MO Hirano, N Nadler, LM TI Standardized, renewable human APC generate long lived antigen specific CTLs for immunotherapy. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1006 BP 282A EP 283A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701006 ER PT J AU Lin, L Ambinder, RF Fisher, DC Mauch, P AF Lin, L Ambinder, RF Fisher, DC Mauch, P CA AIDS Malignancy Consortium TI Epstein-Barr virus "load" in plasma of patients with AIDS malignancy reflects EB viremia and free EB viral DNA (DNA-emia) whereas in EBV(+)Hodgkins lymphoma it reflects only DNA-emia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4850 BP 282B EP 282B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101141 ER PT J AU Weihrauch, MR Jurkiewicz, E Geisen, C Xia, ZN Anderson, KS Diehl, V Wolf, J Bohlen, H Nadler, LM AF Weihrauch, MR Jurkiewicz, E Geisen, C Xia, ZN Anderson, KS Diehl, V Wolf, J Bohlen, H Nadler, LM TI Phase I/II combined immuno-/chemotherapy with CEA derived HLA-A2 restricted CAP-1 peptide and irinotecan, 5-fluorouracil and leucovorin in patients with primary metastatic colorectal cancer. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Cell Ctr Cologne, Cologne, Germany. Univ Cologne, Dept Internal Med 1, Cologne, Germany. Dana Farber Canc Inst, Ctr Med Expt, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1024 BP 287A EP 287A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701024 ER PT J AU Gokmen, E Callander, N Ehsan, A Dostalova, Z Ochoa, L Devore, P Freytes, C AF Gokmen, E Callander, N Ehsan, A Dostalova, Z Ochoa, L Devore, P Freytes, C TI A prospective analysis of B-cell reconstitution after autologous peripheral blood stem cell transplantation using grafts purged in vivo with rituximab in patients with non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ege Univ, Sch Med, Izmir, Turkey. 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 AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4927 BP 301B EP 301B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101218 ER PT J AU Peyvandi, F Palla, R Ardissino, D Foco, L Bernardinelli, L Bauer, K Mannucci, PM AF Peyvandi, F Palla, R Ardissino, D Foco, L Bernardinelli, L Bauer, K Mannucci, PM TI Vagaries of genetic association studies in complex diseases: Thrombospondins and acute myocardial infarction. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Milan, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy. Maggiore Hosp, IRCCS, Milan, Italy. Univ Parma, Dept Cardiol, I-43100 Parma, Italy. Osped Maggiore Parma, Parma, Italy. Univ Pavia, Dipartimento Sci Sanit Applicate, I-27100 Pavia, Italy. Univ Forvie Site, MRC Biostat Unit, Inst Publ Hlth, Cambridge, England. Harvard Univ, Sch Med, Dept Med, Hematol Sect,VA Boston Healthcare, Boston, MA 02115 USA. RI Mannucci, Pier/C-3102-2014 NR 0 TC 3 Z9 3 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1129 BP 314A EP 314A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701129 ER PT J AU Cavusoglu, E El Rouby, S Kunammeni, PB Lau, A Lee, T Hoppensteadt, D Colella, G Zucker, ML LaDuca, FM Fareed, J Marmur, JD AF Cavusoglu, E El Rouby, S Kunammeni, PB Lau, A Lee, T Hoppensteadt, D Colella, G Zucker, ML LaDuca, FM Fareed, J Marmur, JD TI Monitoring low molecular weight heparin (LMWH) during interventional coronary procedures using a sensitive point-of-care assay. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. ITC, Clin Affairs, Edison, NJ USA. ITC, R&D, Edison, NJ USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 1171 BP 326A EP 327A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701171 ER PT J AU Lee, BC McGrath, KE Saito, Y Attar, EC Choi, PS Palis, J Scadden, DT AF Lee, BC McGrath, KE Saito, Y Attar, EC Choi, PS Palis, J Scadden, DT TI Purine/pyrimidine (P2Y) receptor GPR105 expression marks early hematopoietic cells from yolk sac to adult bone marrow. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02215 USA. Univ Rochester, Dept Pediat, Ctr Human Genet & Mol Pediat Dis, Rochester, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1173 BP 327A EP 327A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701173 ER PT J AU Robertson, P Means, TK Luster, AD Scadden, DT AF Robertson, P Means, TK Luster, AD Scadden, DT TI Cell homing to the post-natal thymus is CXCR4 dependent. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1182 BP 329A EP 329A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701182 ER PT J AU Shigematsu, H Reizis, B Iwasaki, H Mizuno, S Leder, P Akashi, K AF Shigematsu, H Reizis, B Iwasaki, H Mizuno, S Leder, P Akashi, K TI Plasmacytoid dendritic cells originate from lymphoid and mycloid pathways, both activating human pre-TCR alpha gene transcription. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1184 BP 329A EP 329A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701184 ER PT J AU Rosenbauer, F Wagner, K Kutok, JL Iwasaki, H Akashi, K Fiering, S Tenen, DG AF Rosenbauer, F Wagner, K Kutok, JL Iwasaki, H Akashi, K Fiering, S Tenen, DG TI Myeloid and B-lymphoid development require high PU.1 expression by a distal element in vivo. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Inst Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Hanover, NH USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 1236 BP 342A EP 342A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701236 ER PT J AU Shelley, CS AF Shelley, CS TI CD11c gene expression in hairy-cell leukemia is dependent upon activation of the proto-oncogenes ras and junD. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 5131 BP 351B EP 352B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537101422 ER PT J AU Battle, TE Frank, D AF Battle, TE Frank, D TI STAT1 activation is associated with induced differentiation of human B cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 5134 BP 352B EP 352B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101425 ER PT J AU Appleman, LJ Chernova, I Nadler, LM Boussiotis, VA AF Appleman, LJ Chernova, I Nadler, LM Boussiotis, VA TI Transcription of SKP2 is uncoupled from mitogenic control in T cell leukemia cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1318 BP 363A EP 363A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701318 ER PT J AU Podar, K Mostoslavsky, G Tai, YT Sattler, M Hayashi, T Catley, LP Hideshima, T Mulligan, RC Chauhan, D Anderson, KC AF Podar, K Mostoslavsky, G Tai, YT Sattler, M Hayashi, T Catley, LP Hideshima, T Mulligan, RC Chauhan, D Anderson, KC TI Critical role for Hck-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin-6-induced proliferation and survival of multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 5198 BP 368B EP 368B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101489 ER PT J AU Munoz, O Fend, F de Beaumont, R Husson, H Astier, A Freedman, AS AF Munoz, O Fend, F de Beaumont, R Husson, H Astier, A Freedman, AS TI Transforming growth factor beta-mediated activation of smad1 in human B cell lymphomas. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Tech Univ Munich, Inst Pathol, D-8000 Munich, Germany. RI Astier, Anne/A-1641-2008 OI Astier, Anne/0000-0002-0144-3431 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1342 BP 369A EP 369A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701342 ER PT J AU Loh, ML Poon, WM Goldwasser, M Vattikuti, S Silverman, LB Cardoso, A Neuberg, DS Shannon, KM Sallan, SE Gilliland, DG AF Loh, ML Poon, WM Goldwasser, M Vattikuti, S Silverman, LB Cardoso, A Neuberg, DS Shannon, KM Sallan, SE Gilliland, DG TI Incidence and outcome of pediatric patients with TEL/AML1 positive acute lymphoblastic leukemia treated on Dana-Farber cancer institute ALL consortium protocol 95-01. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Calif San Francisco, Div Pediat Hematol Oncol, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Acute Lymphoblast Leukemia Consortium, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1362 BP 375A EP 375A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701362 ER PT J AU Soulier, J Leblanc, T Larghero, J Shimamura, A Dastot, H Henri, A Guardiola, P Toubert, A Beuzard, Y Baruchel, A Sigaux, F D'Andrea, AD Gluckman, E AF Soulier, J Leblanc, T Larghero, J Shimamura, A Dastot, H Henri, A Guardiola, P Toubert, A Beuzard, Y Baruchel, A Sigaux, F D'Andrea, AD Gluckman, E TI Analysis of the FANCD2 pathway in Fanconi anemia patients: New diagnosis tool, detection of mosaicisin and subtyping. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Hop St Louis, Dept Hematol, Paris, France. Hop St Louis, Inst Univ Hematol, Paris, France. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1368 BP 377A EP 377A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701368 ER PT J AU Haining, WN Neuberg, D Keczkemethy, H Guenaga, J Silverman, LB Sallan, SE Cardoso, AA Douek, D Nadler, LM Guinan, EC AF Haining, WN Neuberg, D Keczkemethy, H Guenaga, J Silverman, LB Sallan, SE Cardoso, AA Douek, D Nadler, LM Guinan, EC TI T cell deficits at diagnosis and during therapy in children with ALL may preclude antigen specific vaccination. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NIAID, Vaccine Res Ctr, Human Immunol Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1388 BP 382A EP 383A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701388 ER PT J AU Barata, JT Boussiotis, VA Yunes, JA Ferrando, AA Moreau, L Veiga, JP Sallan, SE Look, AT Nadler, LM Cardoso, AA AF Barata, JT Boussiotis, VA Yunes, JA Ferrando, AA Moreau, L Veiga, JP Sallan, SE Look, AT Nadler, LM Cardoso, AA TI An IL-7-dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Lisbon, Sch Med, Inst Mol Med, Unit Tumor Biol, P-1699 Lisbon, Portugal. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1396 BP 385A EP 385A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701396 ER PT J AU Mehta, J Jakob, C Singhal, S Stadtmauer, E Richardson, P Vesole, D Boral, AL Esseltine, DL Sezer, O AF Mehta, J Jakob, C Singhal, S Stadtmauer, E Richardson, P Vesole, D Boral, AL Esseltine, DL Sezer, O TI Bortezomib causes tumor lysis syndrome in approximately 1% of patients with myeloma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Universitatsklinikum Charite, Berlin, Germany. Northwestern Univ, Chicago, IL 60611 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. NR 0 TC 10 Z9 10 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 NOV 16 PY 2003 VL 102 IS 11 MA 5273 BP 386B EP 387B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537101564 ER PT J AU Hayashi, T Hideshima, T Podar, K Munoz, O Richardson, P Hamasaki, M Ishitsuka, K Murphy, A McEnroe, G Chakravarty, S Dugar, S Higgins, LS Chauhan, D Anderson, KC AF Hayashi, T Hideshima, T Podar, K Munoz, O Richardson, P Hamasaki, M Ishitsuka, K Murphy, A McEnroe, G Chakravarty, S Dugar, S Higgins, LS Chauhan, D Anderson, KC TI TGF-beta receptor I kinase inhibitor downregulates cytokine secretion and multiple myeloma cell proliferation in the bone marrow microenvironment. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. SCIOS Inc, Sunnyvale, CA USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 5278 BP 388B EP 388B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101569 ER PT J AU Catley, L Tai, YT Shringarpure, R Son, M Podar, K Burger, R Chauhan, D Hideshima, T Denis, L Tassone, P Munshi, NC Richardson, PG Anderson, KC AF Catley, L Tai, YT Shringarpure, R Son, M Podar, K Burger, R Chauhan, D Hideshima, T Denis, L Tassone, P Munshi, NC Richardson, PG Anderson, KC TI Clinical implications for optimizing the approach to topoisomerase 1 as a therapeutic target in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. Pfizer Inc, Dept Oncol, Groton, CT 06340 USA. RI Catley, Laurence/E-5313-2013 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 5282 BP 389B EP 389B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101573 ER PT J AU Lee, PW Kim, HB Randolph, MA Cina, RA Arellano, R Goodrich, J Rowland, HC Duggan, M Sachs, DH Huang, CA AF Lee, PW Kim, HB Randolph, MA Cina, RA Arellano, R Goodrich, J Rowland, HC Duggan, M Sachs, DH Huang, CA TI Stable multilineage hematopoietic engraftment in swine following in utero bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Plast Surg Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 5326 BP 399B EP 399B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101617 ER PT J AU Kaplan, LD Lee, J Scadden, DT AF Kaplan, LD Lee, J Scadden, DT TI No benefit from rituximab in a randomized phase III trial of CHOP with or without ritukimab for patients with HIV-associated non-Hodgkin's lymphoma: Updated data from AIDS malignancies consortium study 010. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Alabama, Birmingham, AL USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 4 Z9 4 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 NOV 16 PY 2003 VL 102 IS 11 MA 1488 BP 409A EP 410A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701488 ER PT J AU Ballen, KK Becker, PS Yeap, B Matthew, B Henry, DH Ford, PA AF Ballen, KK Becker, PS Yeap, B Matthew, B Henry, DH Ford, PA TI Bloodless transplant: Autologous stem cell transplant can be performed safely without the use of blood product support. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Umass Mem Hlth Care, Worcester, MA USA. Penn Hosp, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 5411 BP 420B EP 421B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537101702 ER PT J AU Feldman, EJ Cortes, J Holyoake, TL Simonsson, B De Angelo, DJ Lipton, JH Turner, AR Baccarani, M Barker, J Guilhot, F Petersdorf, S Silver, RT Wilson, JM Sugrue, M List, AF AF Feldman, EJ Cortes, J Holyoake, TL Simonsson, B De Angelo, DJ Lipton, JH Turner, AR Baccarani, M Barker, J Guilhot, F Petersdorf, S Silver, RT Wilson, JM Sugrue, M List, AF TI Continuous oral Lonafarnib (Sarasar(TM)) for the treatment of patients with myelodysplastic syndrome. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 New York Presbyerian Hosp, Dept Hematol & Oncol, New York, NY USA. MD Anderson Canc Ctr, Houston, TX USA. Glasgow Royal Infirm, Dept Med, Glasgow, Lanark, Scotland. Univ Hosp, Uppsala, Sweden. Dana Farber Canc Inst, Boston, MA 02115 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Inst Ematol & Oncol Med, Bologna, Italy. Univ Minnesota, Minneapolis, MN USA. CHRU La Miletrie, Hop Jean Bernard, Poitiers, France. Seattle Canc Care Alliance, Seattle, WA USA. New York Hosp, New York, NY 10021 USA. Schering Plough Res Inst, Kenilworth, NJ USA. Arizona Canc Ctr, Tucson, AZ USA. NR 0 TC 20 Z9 21 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 NOV 16 PY 2003 VL 102 IS 11 MA 1531 BP 421A EP 421A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701531 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Munshi, NC Joseph, M Libermann, TA Anderson, KC AF Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Munshi, NC Joseph, M Libermann, TA Anderson, KC TI In vitro and in vivo molecular profiling of multiple myeloma (MM) cell interactions with bone marrow (BM) microenvironment: Insight into the role of novel anti-MM agents in counteracting BM-mediated drug-resistance in MM. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Inst Med, Genomics Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2003 VL 102 IS 11 MA 1607 BP 441A EP 441A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701607 ER PT J AU Ryoo, JJ Cole, CE Chauhan, D Hideshima, T Kim, RS Li, C Wong, W Shammas, M Akiyama, M Munshi, NC Richardson, PG Anderson, KC AF Ryoo, JJ Cole, CE Chauhan, D Hideshima, T Kim, RS Li, C Wong, W Shammas, M Akiyama, M Munshi, NC Richardson, PG Anderson, KC TI Transcriptional changes induced by PS-341 treatment of co-cultured multiple myeloma (MM) and bone marrow stromal cells (BMSCs). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Gundersen Lutheran Canc Ctr, Dept Hematol, La Crosse, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1611 BP 442A EP 442A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701611 ER PT J AU von Bergwelt-Baildon, MS Maecker, B Menezes, I Nadler, LM Schultze, JL AF von Bergwelt-Baildon, MS Maecker, B Menezes, I Nadler, LM Schultze, JL TI Migratory capacity to CXCL12, CCL19 and CCL21 of CD40-activated B cells supports their role as cellular adjuvants for cancer vaccines. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1625 BP 445A EP 445A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701625 ER PT J AU Richardson, PG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, D Rajkumar, SV Hideshima, T Bryant, B Mulligan, G Xiao, H Esseltine, D Schenkein, DP Anderson, KC AF Richardson, PG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, D Rajkumar, SV Hideshima, T Bryant, B Mulligan, G Xiao, H Esseltine, D Schenkein, DP Anderson, KC TI Prognostic factors for response parameters and overall survival in patients with multiple myeloma (MM) following treatment with bortezomib. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Millennium Pharm Inc, Cambridge, MA USA. Mayo Clin, Rochester, IL USA. Alta Bates Can Cen, Berkeley, CA USA. St Vincents Comp Can Cen, New York, NY USA. NW Mem Hosp, Chicago, IL 60611 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Arkansas, Little Rock, AR 72204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2003 VL 102 IS 11 MA 1629 BP 446A EP 446A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701629 ER PT J AU Lonial, S Waller, EK Richardson, PG Jagannath, S Francis, D Lehman, M Torre, C Barlogie, B Berenson, JR Singhal, S Schenkein, DP Esseltine, DLW Anderson, J Heffner, LT Anderson, KC AF Lonial, S Waller, EK Richardson, PG Jagannath, S Francis, D Lehman, M Torre, C Barlogie, B Berenson, JR Singhal, S Schenkein, DP Esseltine, DLW Anderson, J Heffner, LT Anderson, KC TI Evaluation of the degree of thrombocytopenia and associated risk factors following bortezomib therapy for relapsed multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Millennium Pharmaceut Inc, Cambridge, England. Northwestern Univ, Chicago, IL 60611 USA. Inst Myeloma & Bone Canc Res, Los Angeles, CA USA. Arkansas Canc Res Ctr, Myeloma & Transplant Res Ctr, Little Rock, AR USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1632 BP 447A EP 447A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701632 ER PT J AU Ghobrial, IM Fonseca, R Greipp, PR Blood, E Rue, M Vesole, D Gertz, M AF Ghobrial, IM Fonseca, R Greipp, PR Blood, E Rue, M Vesole, D Gertz, M TI The initial "Flare" of IgM level after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemia (WM): An eastern cooperative oncology group (ECOG) study. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 7 Z9 7 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 NOV 16 PY 2003 VL 102 IS 11 MA 1637 BP 448A EP 449A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701637 ER PT J AU Tassone, P Gozzini, A Goldmacher, V Shammas, MA Xie, HS Catley, L Burgher, R Hayashi, T Hideshima, T Chauhan, D Munshi, N Anderson, KC AF Tassone, P Gozzini, A Goldmacher, V Shammas, MA Xie, HS Catley, L Burgher, R Hayashi, T Hideshima, T Chauhan, D Munshi, N Anderson, KC TI Antitumor activity of the maytansinoid immunoconjugate B-B4 (B-B4-DM1) against CD138+multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 ImmunoGen Inc, Cambridge, MA USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1641 BP 449A EP 450A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701641 ER PT J AU Hayashi, T Hideshima, T Akiyama, M Podar, K Richardson, P Chauhan, D Treon, SP Anderson, KC AF Hayashi, T Hideshima, T Akiyama, M Podar, K Richardson, P Chauhan, D Treon, SP Anderson, KC TI Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: Clinical application. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1647 BP 451A EP 451A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701647 ER PT J AU Hideshima, T Chauhan, D Hayashi, T Podar, K Akiyama, M Mitsiades, C Mitsiades, N Gong, BQ Bonham, L de Vries, P Munshi, NC Richardson, PG Singer, JW Anderson, KC AF Hideshima, T Chauhan, D Hayashi, T Podar, K Akiyama, M Mitsiades, C Mitsiades, N Gong, BQ Bonham, L de Vries, P Munshi, NC Richardson, PG Singer, JW Anderson, KC TI Anti-tumor activity of lysophosphatidic acid acyltransferase (LPAAT)-beta inhibitors in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Cell Therapeut Inc, Seattle, WA USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1648 BP 451A EP 452A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701648 ER PT J AU Shaffer, J Alexander, SI Dey, B McAfee, S Saidman, S Dombkowski, D Preffer, F Spitzer, TR Sykes, M AF Shaffer, J Alexander, SI Dey, B McAfee, S Saidman, S Dombkowski, D Preffer, F Spitzer, TR Sykes, M TI Origin and phenotype of recovering T cells following haploidentical hematopoietic cell transplantation with medi-507-based non-myeloablative conditioning. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1673 BP 458A EP 459A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701673 ER PT J AU Cina, RA Lee, P Rowland, H Goodrich, JG Spitzer, TR Sachs, DH Huang, CA AF Cina, RA Lee, P Rowland, H Goodrich, JG Spitzer, TR Sachs, DH Huang, CA TI Low dose whole body irradiation combined with a CD3-specific immunotoxin facilitates engraftment without increasing toxicity in a large animal pre-clinical model. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Bone Marrow Transplant Program, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1675 BP 459A EP 459A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701675 ER PT J AU Alyea, EP Kim, HT Fisher, DC Gribben, J Ho, VT Cutler, C Windawi, S Lee, SJ Parik, B Ritz, J Antin, JH Soiffer, RJ AF Alyea, EP Kim, HT Fisher, DC Gribben, J Ho, VT Cutler, C Windawi, S Lee, SJ Parik, B Ritz, J Antin, JH Soiffer, RJ TI Second hematopoietic stem cell transplantation using a nonmyeloablative approach: Low toxicity using a fludarabine and intravenous busulfan regimen. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 5571 BP 461B EP 461B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101862 ER PT J AU De Angelo, DJ Hochberg, EP Alyea, EP Longtine, J Lee, S Galinsky, I Parekkedon, B Ritz, J Antin, JH Stone, RM Soiffer, RJ AF De Angelo, DJ Hochberg, EP Alyea, EP Longtine, J Lee, S Galinsky, I Parekkedon, B Ritz, J Antin, JH Stone, RM Soiffer, RJ TI Extended follow-up of patients treated with imatinib mesylate (Gleevec (R)) for CML relapse following allogeneic transplantation: Durable cytogenetic remission and conversion to complete donor chimerism without GVHD. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 5573 BP 462B EP 462B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101864 ER PT J AU Ballen, KK Haley, NR Kurtzberg, J Lane, TA Lindgren, BR Miller, JP Newman, BH McCullough, J AF Ballen, KK Haley, NR Kurtzberg, J Lane, TA Lindgren, BR Miller, JP Newman, BH McCullough, J TI Outcomes of 138 adult and pediatric patients undergoing cord blood transplantation from large cord blood bank. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Amer Red Cross, Cord Blood Program, Worcester, MA USA. Amer Red Cross, Biomed Serv, Arlington, VA USA. Duke Univ, Med Ctr, Carolinas Cord Blood Bank, Durham, NC USA. Amer Red Cross, Cord Blood Program, Portland, OR USA. Univ Minnesota, Amer Red Cross, Minneapolis, MN 55455 USA. Amer Red Cross Program, Cord Blood Program, St Paul, MN USA. Amer Red Cross, Cord Blood Bank, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1747 BP 479A EP 479A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701747 ER PT J AU Borrello, IM Levitsky, HI Stock, W Scher, D Damon, LE Linker, CA DeAngelo, DJ Alyea, EP Nelson, L Hege, KM AF Borrello, IM Levitsky, HI Stock, W Scher, D Damon, LE Linker, CA DeAngelo, DJ Alyea, EP Nelson, L Hege, KM TI Posttransplant immunotherapy with a GM-CSF-based tumor vaccine (GVAX (R)) following autologous stem cell transplant (ASCT) for acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Chicago, Chicago, IL 60637 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cell Genesys, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1791 BP 492A EP 492A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701791 ER PT J AU Friedberg, JW Lepisto, E Rodriguez, MA Ottensen, R LaCasce, AS Nademanee, AP Millenson, M Czuczman, M Niland, J Zelenetz, AD Weeks, J AF Friedberg, JW Lepisto, E Rodriguez, MA Ottensen, R LaCasce, AS Nademanee, AP Millenson, M Czuczman, M Niland, J Zelenetz, AD Weeks, J TI Utilization of rituximab therapy in patients (pts) with newly diagnosed follicular (FL) and diffuse large B cell (DLCL) non-Hodgkin's lymphoma (NHL) in the United States: An analysis from the national comprehensive cancer network (NCCN) NHL outcomes project. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. Natl Comprehens Canc Network, Rockledge, PA USA. MD Anderson Canc Ctr, Houston, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. City Hope Med Ctr, Duarte, CA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1800 BP 494A EP 494A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701800 ER PT J AU Gazda, HT Sanoudou, D Beggs, AH Sieff, CA AF Gazda, HT Sanoudou, D Beggs, AH Sieff, CA TI Identification of candidate genes on chromosome 8p in Diamond Blackfan Anemia using microarrays. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1837 BP 505A EP 505A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701837 ER PT J AU Tzachanis, D Appleman, LJ van Puijenbroek, AAAFL Berezovskaya, A Nadler, LM Boussiotis, VA AF Tzachanis, D Appleman, LJ van Puijenbroek, AAAFL Berezovskaya, A Nadler, LM Boussiotis, VA TI Differential localization and function of ARF6 in anergic T cells: A candidate marker for their phenotypic identificatiion. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1927 BP 526A EP 526A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701926 ER PT J AU Tavares, MJ Freeman, GJ van Grotel, M Henrique, D Carlesso, N Nadler, LM Cardoso, AA AF Tavares, MJ Freeman, GJ van Grotel, M Henrique, D Carlesso, N Nadler, LM Cardoso, AA TI Inhibition of vascular endothelium by the notch-ligand delta-4 unveils a novel therapeutic target. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Inst Mol Med, Dev Biol Unit, Lisbon, Portugal. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1944 BP 531A EP 531A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701943 ER PT J AU Wang, H Jiang, XH Schildmeyer, L Liao, D Yang, F Yang, XF Durante, W Rumbaut, RE Bryan, RM Schafer, AI AF Wang, H Jiang, XH Schildmeyer, L Liao, D Yang, F Yang, XF Durante, W Rumbaut, RE Bryan, RM Schafer, AI TI Hyperhomocysteinemia impairs endothelial function by nitric oxide inhibition in cystathionine beta-synthase knockout mice and in aortic endothelial cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1947 BP 531A EP 531A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701946 ER PT J AU Wang, H Tan, HW Yang, F Liao, D Shi, CV Yang, XF Durante, W Schafer, AI AF Wang, H Tan, HW Yang, F Liao, D Shi, CV Yang, XF Durante, W Schafer, AI TI Hyperhomocysteinemia promotes vascular fibrosis following vascular injury in cystathionine B-synthase knockout mice. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Nova Pharmaceut Corp, Summit, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1952 BP 532A EP 533A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701951 ER PT J AU Patel, KV Wijelath, ES Patel, YM Sumathipala, R Sobel, MS Murray, J Seago, J Savidge, GF Rahman, S AF Patel, KV Wijelath, ES Patel, YM Sumathipala, R Sobel, MS Murray, J Seago, J Savidge, GF Rahman, S TI Hepatocyte growth factor (HGF) binding domains on fibronectin and vitronectin promote enhanced endothelial cell migration via a specific ras and PI3-kinase dependent pathway. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 St Thomas Hosp, GKT Sch Med, Div Med, Coagulat Res Lab, London, England. Univ Washington, Div Vasc Surg, Sch Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 1955 BP 533A EP 533A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701954 ER PT J AU Larghero, J Soulier, J Leblanc, T Dastot, H Ternaux, B Guardiola, P Baruchel, A D'Andrea, AD Marolleau, JP Gluckman, E AF Larghero, J Soulier, J Leblanc, T Dastot, H Ternaux, B Guardiola, P Baruchel, A D'Andrea, AD Marolleau, JP Gluckman, E TI Stem cell clonogenic capacities in Fanconi Anemia patients are linked to somatic mosaicism. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Hop St Louis, Dept Hematol, Paris, France. Hop St Louis, Inst Hematol, Paris, France. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2070 BP 563A EP 563A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702068 ER PT J AU Rodrigues, NP Forkert, R Dombkowski, DM Zhang, JL Orford, KW Orkin, SH Enver, T Vyas, P Scadden, DT AF Rodrigues, NP Forkert, R Dombkowski, DM Zhang, JL Orford, KW Orkin, SH Enver, T Vyas, P Scadden, DT TI Haploinsufficiency of GAtA-2 effects adult stem cell homeostasis. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Oxford, Weatherall Inst Mol Med, MRC, Haematol Unit, Oxford, England. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 2078 BP 565A EP 565A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702076 ER PT J AU Hock, H Hamblen, MJ Rooke, HM Schindler, R Fujiwara, Y Orkin, SH AF Hock, H Hamblen, MJ Rooke, HM Schindler, R Fujiwara, Y Orkin, SH TI Loss of Gfi-1 compromises hematopoietic stem cell function. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2088 BP 567A EP 568A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702086 ER PT J AU Rodrigues, NP Cheng, T Cohen, KS Forkert, R Shao, Y Vyas, P Scadden, DT AF Rodrigues, NP Cheng, T Cohen, KS Forkert, R Shao, Y Vyas, P Scadden, DT TI Stem cells deficient in p21Cip1/Waf1 compete poorly in establishing long-term bone marrow hematopoiesis. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Pittsburgh Canc Inst, Pittsburgh, PA 15213 USA. Univ Oxford, Weatherall Inst Mol Med, MRC, Haematol Unit, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2097 BP 570A EP 570A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702095 ER PT J AU Hsu, K Traver, D Kutok, JL Hagen, A Liu, TX Paw, BH Rhodes, J Berman, J Zon, LI Kanki, J Look, AT AF Hsu, K Traver, D Kutok, JL Hagen, A Liu, TX Paw, BH Rhodes, J Berman, J Zon, LI Kanki, J Look, AT TI Expression of Pu.1 in embryonic and adult transgenic zebrafish. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2112 BP 574A EP 574A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702110 ER PT J AU Burel, S Yan, M Peterson, L Iwasaki, H Hines, R Kanbe, E Boyapati, A Akashi, K Zhang, DE AF Burel, S Yan, M Peterson, L Iwasaki, H Hines, R Kanbe, E Boyapati, A Akashi, K Zhang, DE TI When less is more: Truncation of AML1-ETO (RUNX1-MTG8) fusion protein results in a rapid onset of acute myeloid leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Scripps Res Inst, La Jolla, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2154 BP 585A EP 585A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702152 ER PT J AU Okuda, K Sato, Y Sonoda, Y Griffin, JD AF Okuda, K Sato, Y Sonoda, Y Griffin, JD TI Direct binding of GRB2 to the TEL/ARG fusion protein via tyrosine 314 in TEL contributes the activation of Raf/MAPK pathway and hyper-responsiveness to IL-3. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Kyoto Prefectural Univ Med, Kyoto 602, Japan. Int Med Ctr Japan, Tokyo, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2169 BP 588A EP 589A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702167 ER PT J AU Scheijen, BN Griffin, JD AF Scheijen, BN Griffin, JD TI Inhibition of FOXO3A function is essential for survival of human leukemia cells with genetic FLT3 abnormalities. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2170 BP 589A EP 589A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702168 ER PT J AU Cools, J Quentmeier, H Huntly, BJP Marynen, P Griffin, JD Drexler, HG Gilliland, DG AF Cools, J Quentmeier, H Huntly, BJP Marynen, P Griffin, JD Drexler, HG Gilliland, DG TI The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA positive chronic eosinophilic leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Univ Leuven VIB, Ctr Human Genet, Louvain, 02115, Belgium. German Collect Microorgan & Cell Cultures, Dept Human & Anim Cell Cultures, Braunschweig, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2185 BP 593A EP 593A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702183 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Kung, AL Anderson, KC AF Mitsiades, CS Mitsiades, N McMullan, CJ Kung, AL Anderson, KC TI IGF-II (IGF-2) is a major proliferative/anti-apoptotic cytokine and a therapeutic target in MM, other hematologic neoplasias and solid tumors. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2188 BP 593A EP 594A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702186 ER PT J AU Estey, EH Fisher, T Giles, F Feldman, EJ Ehninger, G Schiller, GJ Klimek, VM Nimer, SD De Angelo, DJ Gilliland, DG Fox, E Wang, YF Rosamilia, M Resta, D Cohen, P Stone, RM AF Estey, EH Fisher, T Giles, F Feldman, EJ Ehninger, G Schiller, GJ Klimek, VM Nimer, SD De Angelo, DJ Gilliland, DG Fox, E Wang, YF Rosamilia, M Resta, D Cohen, P Stone, RM TI A randomized phase II trial of the tyrosine kinase inhibitor PKC412 in patients (pts) with acute myeloid leukemia (AML)/high-risk myelodysplastic syndromes (MDS) characterized by wild-type (WT) or mutated FLT3. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Mainz, Ctr Canc, Mainz, Germany. Cornell Univ, Ctr Canc, New York, NY USA. Univ Carl Gustav Carus, Dresden, Germany. Univ Calif Los Angeles, Ctr Med, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Ctr, Boston, MA 02115 USA. Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 7 Z9 9 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 NOV 16 PY 2003 VL 102 IS 11 MA 2270 BP 614A EP 615A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702268 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Treon, SP Richardson, PG Munshi, NC Joseph, M Libermann, T Anderson, K AF Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Treon, SP Richardson, PG Munshi, NC Joseph, M Libermann, T Anderson, K TI Heat shock protein 90 (hsp90) inhibitors: A novel class of agents with activity against Waldenstrom's macroglobulinemia (WM): Pre-clinical studies, and molecular profiling and clinical implications. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. Harvard Univ, Inst Med, Genom Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2395 BP 648A EP 648A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702393 ER PT J AU Mohi, MG Boulton, C Gu, TL Sternberg, DW Neuberg, D Griffin, JD Gilliland, DG Neel, BG AF Mohi, MG Boulton, C Gu, TL Sternberg, DW Neuberg, D Griffin, JD Gilliland, DG Neel, BG TI Combination of rapamycin with PTK inhibitors for the treatment of leukemias caused by oncogenic PTKs. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2413 BP 652A EP 652A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702411 ER PT J AU Banerji, L Churchill, WH Griffin, JD AF Banerji, L Churchill, WH Griffin, JD TI Identification of an imatinib mesylate sensitive phosphoprotein in primary polycythemia vera cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 2461 BP 664A EP 664A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702459 ER PT J AU Rassenti, LZ Toy, TL Huynh, L Greaves, A Gribben, JG Keating, MJ Rai, KR Flinn, IW Byrd, JC Kay, NE Goldin, LR Caporaso, NE Kipps, TJ AF Rassenti, LZ Toy, TL Huynh, L Greaves, A Gribben, JG Keating, MJ Rai, KR Flinn, IW Byrd, JC Kay, NE Goldin, LR Caporaso, NE Kipps, TJ TI High similarity between familial and sporadic cases of chroni lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Long Isl Jewish Med Ctr, New York, NY USA. Johns Hopkins Univ, Ctr Canc, Baltimore, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Mayo Clin, Rochester, MN USA. Natl Canc Inst, Rockville, MD USA. Univ Calif San Diego, CLL Res Consortium, La Jolla, CA 92093 USA. NR 0 TC 4 Z9 4 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 NOV 16 PY 2003 VL 102 IS 11 MA 2481 BP 670A EP 670A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702479 ER PT J AU Gonzalez-Paz, N Qu, GZ McClure, R Price-Troska, T Blood, E Rajkumar, SV Oken, MM Kay, NE Kyle, RA Van Wier, SA Henderson, KJ Greipp, PR Van Ness, BG Fonseca, R AF Gonzalez-Paz, N Qu, GZ McClure, R Price-Troska, T Blood, E Rajkumar, SV Oken, MM Kay, NE Kyle, RA Van Wier, SA Henderson, KJ Greipp, PR Van Ness, BG Fonseca, R TI Clinical and biological implications of p16 methylation in of multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Dept Internal Med, Rochester, MN USA. Mayo Clin, Dept Lab Med, Rochester, MN USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. N Mem Canc Ctr, Robbinsdale, MN USA. Univ Minnesota, Dept Genet, Minneapolis, MN USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 2509 BP 677A EP 677A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702507 ER PT J AU Zhao, FY Kiffmeyer, WR Blood, E Rue, M Fonseca, R Oken, MM Kay, NE Kyle, RA Greipp, PR Van Ness, BG AF Zhao, FY Kiffmeyer, WR Blood, E Rue, M Fonseca, R Oken, MM Kay, NE Kyle, RA Greipp, PR Van Ness, BG TI Polymorphic variations in myeloma cytokine genes are associated with treatment outcomes in phase III ECOG trial E9486. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Minnesota, Minneapolis, MN USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. N Mem Med Ctr, Robbinsdale, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2511 BP 678A EP 678A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702509 ER PT J AU Shammas, MA Reis, RJS Koley, H Desarnaud, F Li, C Anderson, KC Munshi, NC AF Shammas, MA Reis, RJS Koley, H Desarnaud, F Li, C Anderson, KC Munshi, NC TI Elevated homologous recombination can be targeted to prevent chromosomal rearrangements leading to initiation and progression of multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Boston VA Hlth Care Syst, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Cent Arkansas Vet Hlth Care Syst, Little Rock, AR USA. RI Shmookler Reis, Robert/C-4112-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2516 BP 679A EP 679A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702514 ER PT J AU Shammas, MA Reis, RJS Koley, H Shah, S Desarnaud, F Tassone, P Anderson, KC Munshi, NC AF Shammas, MA Reis, RJS Koley, H Shah, S Desarnaud, F Tassone, P Anderson, KC Munshi, NC TI Elevated endonuclease activity affects homologous recombination and genomic re-arrangementsin MM cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Boston VA Hlth Care Syst, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Arkansas Med Sci, Little Rock, MA USA. Cent Arkansas Vet Hlth Care Syst, Little Rock, MA USA. RI Shmookler Reis, Robert/C-4112-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2515 BP 679A EP 679A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702513 ER PT J AU Treon, SP Braverman, E Branagan, AR Masotta, S Listewnik, M Morton, C Lee, C AF Treon, SP Braverman, E Branagan, AR Masotta, S Listewnik, M Morton, C Lee, C TI Deletions in 6q21-22 are commonly present in patients with familial and non-familial Waldenstrom's macroglobulinemia and IgM monoclonal gammopathy of unknown significance (MGUS). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Waldenstroms Macroglobulinemia Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2526 BP 682A EP 682A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702524 ER PT J AU McMullan, CJ Mitsiades, N Joseph, M Libermann, T Mitsiades, CS Anderson, KC AF McMullan, CJ Mitsiades, N Joseph, M Libermann, T Mitsiades, CS Anderson, KC TI Molecular profiling studies in a chemo-sensitive multiple myeloma (MM) cell line model and its chemo-resistant sub-lines: Insight into the regulation of tumor cell responsiveness to various cytotoxic chemotherapeutic agents. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Inst Med, Genom Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2531 BP 683A EP 683A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702529 ER PT J AU Ishitsuka, K Hideshima, T Hamasaki, M Hayashi, T Podar, K Chauhan, D Tai, YZ Tassone, P Jain, J Fram, R Anderson, KC AF Ishitsuka, K Hideshima, T Hamasaki, M Hayashi, T Podar, K Chauhan, D Tai, YZ Tassone, P Jain, J Fram, R Anderson, KC TI A novel inosine monophosphate dehydrogenase inhibitor VX-944 overcomes drug resistances in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Vertex Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2535 BP 684A EP 685A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702534 ER PT J AU Tassone, P Gozzini, A Goldmacher, VS Shammas, MA Shringarpure, R Catley, L Hayashi, T Hideshima, T Chauhan, D Anderson, KC Munshi, N AF Tassone, P Gozzini, A Goldmacher, VS Shammas, MA Shringarpure, R Catley, L Hayashi, T Hideshima, T Chauhan, D Anderson, KC Munshi, N TI In vitro and in vivo antitumor activity of the maytansinoid immunoconjugate BB-10901 (huN901-DM1) on CD56+multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Immunogen Inc, Cambridge, MA USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2554 BP 690A EP 690A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702553 ER PT J AU Treon, SP Branagan, AR Anderson, KC AF Treon, SP Branagan, AR Anderson, KC TI Paradoxical increases in serum IgM levels and serum viscosity following rituximab therapy in patients with Waldenstrom's macroglobulinemia (WM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Waldenstroms Macroglobulinemia Program, Boston, MA 02115 USA. NR 0 TC 2 Z9 3 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 NOV 16 PY 2003 VL 102 IS 11 MA 2555 BP 690A EP 690A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702554 ER PT J AU Friedenberg, WR Rue, M Dalton, W Schiffer, CA Shustik, C Cella, D Sonneveld, P Greipp, PR Kyle, R AF Friedenberg, WR Rue, M Dalton, W Schiffer, CA Shustik, C Cella, D Sonneveld, P Greipp, PR Kyle, R TI Phase 3 study of the multi-drug resistant modulator PSC-833 in relapsing or refractory multiple myeloma: An intergroup study led by ECOG (E1A45). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Guthrie Clin, Sayre, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wayne State Univ, Sch Med, Haper Hosp, Detroit, MI USA. McGill Univ, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. Northwestern Univ, CORE, Evanston, IL USA. H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2559 BP 691A EP 691A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702558 ER PT J AU Podar, K Tai, YT Carvalho, P Catley, LP Shringarpure, R Burger, R Hayashi, T Pandite, LN Kumar, R Pellman, D Hideshima, T Chauhan, D Anderson, KC AF Podar, K Tai, YT Carvalho, P Catley, LP Shringarpure, R Burger, R Hayashi, T Pandite, LN Kumar, R Pellman, D Hideshima, T Chauhan, D Anderson, KC TI The pan-inhibitor of VEGF receptors, GW654652 blocks growth and migration of multiple myeloma cells in the bone marrow microenvironment. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat Hematol & Oncol, Dana Farber Canc Inst, Boston, MA USA. Glaxo Inc, Res Triangle Pk, NC 27709 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 2563 BP 692A EP 692A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702562 ER PT J AU Rajkumar, SV Richardson, PG Gertz, MA Lacy, MQ Dispenzieri, A Greipp, PR Witzig, TE Schlossman, RL Sidor, C Anderson, KC AF Rajkumar, SV Richardson, PG Gertz, MA Lacy, MQ Dispenzieri, A Greipp, PR Witzig, TE Schlossman, RL Sidor, C Anderson, KC TI Novel therapy with 2-methoxyestradiol (2ME2) for the treatment of relapsed and plateau phase multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA USA. Mayo Clin, Rochester, MN USA. EntreMed Inc, Rockville, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2564 BP 692A EP 692A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702563 ER PT J AU Mitsiades, CS Richardson, PG Menon, K Rouleau, C Momtaz, P Mitsiades, N Teicher, B Iacobelli, M Anderson, KC AF Mitsiades, CS Richardson, PG Menon, K Rouleau, C Momtaz, P Mitsiades, N Teicher, B Iacobelli, M Anderson, KC TI Defibrotide (DF) has anti-neoplastic activity against multiple myeloma: Clinical implications for the incorporation of DF in cytotoxic chemotherapeutic regimens. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA USA. Gentium SpA, Como, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2567 BP 693A EP 693A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702566 ER PT J AU Vasir, B Rosenblatt, J Wu, ZW Mcdermott, D Joyce, R Levine, JD Ottaway, J Giallombardo, N Hurley, D Listewnik, M Avigan, D AF Vasir, B Rosenblatt, J Wu, ZW Mcdermott, D Joyce, R Levine, JD Ottaway, J Giallombardo, N Hurley, D Listewnik, M Avigan, D TI Dendritic cell chimerism and function following nonmyeloablative allogeneic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2575 BP 695A EP 695A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702574 ER PT J AU Rubio, MT Zhao, GL Kattleman, K Sykes, M AF Rubio, MT Zhao, GL Kattleman, K Sykes, M TI Mechanisms of donor graft rejection and antitumor effects induced by recipient leukocyte infusion in mixed chimeras prepared with nonmyeloablative conditioning: Differential roles of recipient CD4 and CD8 T cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2589 BP 699A EP 699A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702588 ER PT J AU Rubio, MT Sykes, M AF Rubio, MT Sykes, M TI Role of indirect presentation of donor antigens in the antitumor responses induced by recipient leukocyte infusion in mixed chimeras prepared with nonmyeloablative conditioning. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2592 BP 700A EP 700A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702591 ER PT J AU Alyea, EP Kim, HT Ho, V Cutler, C Gribben, J DeAngelo, D Lee, SJ Ritz, J Stone, RM Antin, JH Soiffer, RJ AF Alyea, EP Kim, HT Ho, V Cutler, C Gribben, J DeAngelo, D Lee, SJ Ritz, J Stone, RM Antin, JH Soiffer, RJ TI Comparable progression free survival and overall survival for patients > 50 years of age receiving allogeneic nonmyeloablative and myeloablative transplantation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2602 BP 703A EP 703A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702601 ER PT J AU Lee, SJ Loberiza, FR Logan, B Soiffer, RJ Alyea, EP Cutler, C Ho, VT Richardson, P Antin, JH AF Lee, SJ Loberiza, FR Logan, B Soiffer, RJ Alyea, EP Cutler, C Ho, VT Richardson, P Antin, JH TI Routine screening for psychosocial distress following hematopoietic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Med Coll Wisconsin, Hlth Policy Inst, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2604 BP 704A EP 704A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702603 ER PT J AU Ho, VT Sackstein, R Cutler, C Hochberg, E Alyea, EP Lee, SJ Antin, JH Soiffer, JS AF Ho, VT Sackstein, R Cutler, C Hochberg, E Alyea, EP Lee, SJ Antin, JH Soiffer, JS TI High incidence of peri-engraftment fever and rash in patients after CD8 T cell depleted allogeneic myeloablative peripheral blood stem cell transplantation (PBSCT). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 2627 BP 710A EP 710A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702626 ER PT J AU Alyea, EP Neuberg, D Cutler, C Parik, B Windawi, S Fisher, D Ho, V Gribben, J Ritz, J Spitzer, T Soiffer, R Antin, J AF Alyea, EP Neuberg, D Cutler, C Parik, B Windawi, S Fisher, D Ho, V Gribben, J Ritz, J Spitzer, T Soiffer, R Antin, J TI Sirolimus, tacrolimus and low dose methotrexate as graft versus host disease prophylaxis after matched related and unrelated nonmyeloablative transplantation is well tolerated and associated with a low incidence of acute GVHD. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 2632 BP 711A EP 711A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702631 ER PT J AU Lee, SJ Kim, HT Alyea, EP Ho, VT Cutler, C Antin, JH Soiffer, RJ AF Lee, SJ Kim, HT Alyea, EP Ho, VT Cutler, C Antin, JH Soiffer, RJ TI Quality of life associated with acute and chronic graft-vs.-host disease. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2669 BP 721A EP 722A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702668 ER PT J AU Loberiza, F Soiffer, RJ Zhang, MJ Alyea, EP Cutler, C Ho, VT Richardson, P Antin, JH Lee, SJ AF Loberiza, F Soiffer, RJ Zhang, MJ Alyea, EP Cutler, C Ho, VT Richardson, P Antin, JH Lee, SJ TI Depression and anxiety before hematopoietic stem cell transplantation are associated with increased mortality. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Med Coll Wisconsin, Hlth Policy Inst, Milwaukee, WI 53226 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2668 BP 721A EP 721A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702667 ER PT J AU Spitzer, TR Sykes, M Delmonico, F Tolkoff-Rubin, N McAfee, SL Dey, BR Ballen, K Sackstein, R Colby, C Saidman, S Ramos, EL Seyfert-Margolis, V Sachs, DH Cosimi, AB AF Spitzer, TR Sykes, M Delmonico, F Tolkoff-Rubin, N McAfee, SL Dey, BR Ballen, K Sackstein, R Colby, C Saidman, S Ramos, EL Seyfert-Margolis, V Sachs, DH Cosimi, AB TI Tolerance and antitumor responses following combined HLA-matched nonmyeloablative bone marrow and kidney transplantation for multiple myeloma with end-stage renal disease. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NIAID, Immune Tolerance Network, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2692 BP 728A EP 728A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702691 ER PT J AU Dey, BR McAfee, SL Caron, M Colby, C Anderson, D Abigail Preffer, F Saidman, S Sachs, DH Sykes, M Spitzer, TR AF Dey, BR McAfee, SL Caron, M Colby, C Anderson, D Abigail Preffer, F Saidman, S Sachs, DH Sykes, M Spitzer, TR TI Cellular contents within bone marrow and GCSF-mobilized peripheral blood stem cell grafts and their influence on clinical outcomes following nonmyeloablative HLA-matched stem cell transplant. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2699 BP 730A EP 730A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702698 ER PT J AU Wadleigh, M Zahrieh, D Stone, RM Soiffer, RJ Robertson, M Ritz, J Alyea, EP AF Wadleigh, M Zahrieh, D Stone, RM Soiffer, RJ Robertson, M Ritz, J Alyea, EP TI Addition of anti-CD33 purged autologous peripheral blood stem cells to purged marrow speeds time to engraftment compared with purged autologous marrow alone for acute myelogenous leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2734 BP 741A EP 741A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702734 ER PT J AU Prchal, JT Pospisilova, D Mims, MP Priwitzerova, M Indrak, K Ponka, P Guan, YL Divoky, V AF Prchal, JT Pospisilova, D Mims, MP Priwitzerova, M Indrak, K Ponka, P Guan, YL Divoky, V TI Identification of the first human mutation of DMT1 (Nramp2) in a patient with microcytic anemia and iron overload. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. McGill Univ, Montreal, PQ, Canada. Houston VA Med Ctr, Houston, TX USA. RI Ponka, Prem/A-4123-2011 NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 2781 BP 754A EP 754A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702781 ER PT J AU Means, RT Dallalio, G Fleury, T AF Means, RT Dallalio, G Fleury, T TI Serum hepcidin and cytokines in anemic patients. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. Med Univ S Carolina, Div Hematol Oncol, Charleston, SC USA. RI Means, Robert/A-4454-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2792 BP 757A EP 757A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702792 ER PT J AU Wu, CJ Rogers, SA Kutok, JL Hochberg, EP Biernacki, M Bridges, KR Antin, JH Ritz, J AF Wu, CJ Rogers, SA Kutok, JL Hochberg, EP Biernacki, M Bridges, KR Antin, JH Ritz, J TI Erythroid chimerism in peripheral blood exceeds bone marrow following non-myeloablative stem cell transplantation in adults with sickle cell anemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2816 BP 763A EP 763A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702816 ER PT J AU Li, LQ Berezovskaya, A Nadler, LM Boussiotis, VA AF Li, LQ Berezovskaya, A Nadler, LM Boussiotis, VA TI Independent, CDK- and GRB2-mediated regulatory functions of p27 control T cell activation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2834 BP 768A EP 768A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702834 ER PT J AU Italiano, JE Schulze, H Hartwig, JH Shivdasani, RA Osborn, EH AF Italiano, JE Schulze, H Hartwig, JH Shivdasani, RA Osborn, EH TI Relationship of microtubule dynamics to proplatelet elongation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol & Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 2872 BP 777A EP 777A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702872 ER PT J AU Resendiz, JC Lassila, R Kroll, MH AF Resendiz, JC Lassila, R Kroll, MH TI Distinct mechanisms of protease-activated receptor (PAR) 1 - and PAR 4-induced phosphatidylinositol 3-kinase activation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Wihuri Res Inst, SF-00140 Helsinki, Finland. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2870 BP 777A EP 777A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702870 ER PT J AU Feng, SJ Lu, X Kroll, MH AF Feng, SJ Lu, X Kroll, MH TI The cytoplasmic domain of glycoprotein (Gp) Ib alpha couples von Willebrand factor (VWF) - Dependent cell contact with rolling and stable adhesion. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2886 BP 781A EP 781A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702886 ER PT J AU Kutok, JL Yang, X Salahuddin, S Badovinac, RL Imitola, J Raddassi, K Lebedeva, T Folkerth, RD Donato, JL Lim, KH Abbott, J Chinami, M Saito, H Shirakawa, T Lawitts, J Sayegh, MH Khoury, S Scadden, DT Adra, C AF Kutok, JL Yang, X Salahuddin, S Badovinac, RL Imitola, J Raddassi, K Lebedeva, T Folkerth, RD Donato, JL Lim, KH Abbott, J Chinami, M Saito, H Shirakawa, T Lawitts, J Sayegh, MH Khoury, S Scadden, DT Adra, C TI HTm4 is a marker of hematopoiesis and early central nervous system development in mouse: Cloning, genomic organization, protein expression and functional characterization of the murine homologue of human HTm4. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. Kyushu Womens Univ, Dept Nutr, Fukuoka, Japan. Showa Univ, Sch Med, Tokyo, Japan. Natl Res Inst Child Hlth & Dev, Dept Allergy & Immunol, Tokyo, Japan. RIKEN, Res Ctr Allergy & Immunol, Res Team Allergy Transcriptome, Tokyo, Japan. Kyoto Univ, Grad Sch Publ Hlth, Dept Hlth Promot & Human Behav, Kyoto, Japan. RIKEN, SNP, Typing Ctr, Tokyo, Japan. Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3072 BP 829A EP 829A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703072 ER PT J AU Xu, K Chung, D Glasow, A Jing, YK Guidez, F Stegmaier, K Golub, TR Zelent, A Waxman, S AF Xu, K Chung, D Glasow, A Jing, YK Guidez, F Stegmaier, K Golub, TR Zelent, A Waxman, S TI Dithiophenes potentiate differentiation of APL cells by lowering the threshold for ligand mediated co-repressor/co-activator exchange with RAR alpha and enhancing changes in ATRA regulated gene expression. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Inst Canc Res, Leukaemia Res Fund Ctr, London SW3 6JB, England. Mt Sinai Sch Med, Dept Med, New York, NY USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RI Guidez, Fabien/B-3750-2009 NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 3195 BP 859A EP 859A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703195 ER PT J AU Ikeda, T Kimura, F Sato, K Nakata, Y Sporn, M Motoyoshi, K Kufe, D AF Ikeda, T Kimura, F Sato, K Nakata, Y Sporn, M Motoyoshi, K Kufe, D TI CDDO compounds induces apoptosis in malignant cells by disruption of intracellular redox imbalances. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Def Med Coll, Dept Internal Med 3, Tokorozawa, Saitama 359, Japan. Dartmouth Coll, Dept Pharmacol, Hanover, NH 03755 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3208 BP 862A EP 862A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703208 ER PT J AU Haining, WN Cardoso, AA Fleming, M Neuberg, DS De Angelo, DJ Silverman, LB Stone, RM Sallan, SE Guinan, EC Nadler, LM AF Haining, WN Cardoso, AA Fleming, M Neuberg, DS De Angelo, DJ Silverman, LB Stone, RM Sallan, SE Guinan, EC Nadler, LM TI Rapid disease progression precludes autologous tumor vaccination in patients with relapsed ALL. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3282 BP 882A EP 882A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703282 ER PT J AU Feuerhake, F Dal Cin, P Kurtin, P Pasqualucci, L Savage, KJ Kutok, JL Neuberg, D Aguiar, RC Monti, S Ladd, C Cattoretti, G Pinkus, GS Harris, NL Habermann, T Golub, TR Dalla-Favera, R Aster, JC Shipp, MA AF Feuerhake, F Dal Cin, P Kurtin, P Pasqualucci, L Savage, KJ Kutok, JL Neuberg, D Aguiar, RC Monti, S Ladd, C Cattoretti, G Pinkus, GS Harris, NL Habermann, T Golub, TR Dalla-Favera, R Aster, JC Shipp, MA TI Genetic heterogeneity in diffuse large B-cell lymphoma (DLBCL): Chromosomal translocations and increased copy numbers, gene amplification, and aberrant somatic hypermutation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA USA. Mayo Clin, Rochester, MN USA. Columbia Univ, Inst Canc Genet, New York, NY USA. MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3319 BP 892A EP 892A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703319 ER PT J AU Kriangkum, J Taylor, BJ Treon, SP Mant, MJ Belch, AR Pilarski, LM AF Kriangkum, J Taylor, BJ Treon, SP Mant, MJ Belch, AR Pilarski, LM TI Clonotypic B cells of Waldenstrom's macroglobulinemia are IgM(+)IgD(+) memory cells that frequently lack CD27. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. Dana Farber Canc Inst, Boston, MA USA. Univ Alberta, Edmonton, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3324 BP 893A EP 894A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703324 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Treon, SP Richardson, PG Munshi, NC Joseph, M Libermann, TA Anderson, KC AF Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Treon, SP Richardson, PG Munshi, NC Joseph, M Libermann, TA Anderson, KC TI Pre-clinical studies in support of the use of histone deacetylase (HDAC) inhibitors for the treatment of Waldenstrom's macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Inst Med, Genomics Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3357 BP 902A EP 902A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703357 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Treon, SP Richardson, PG Munshi, NC Joseph, M Libermann, TA Anderson, KC AF Mitsiades, CS Mitsiades, N McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Chauhan, D Treon, SP Richardson, PG Munshi, NC Joseph, M Libermann, TA Anderson, KC TI Immunomodulatory thalidomide derivatives have activity against tumor cells from Waldenstrom's macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Inst Med, Genom Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3360 BP 903A EP 903A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703360 ER PT J AU Strauss, SJ Lui, W Schenkein, D Shringarpure, R Anderson, K Lister, TA Joel, SP AF Strauss, SJ Lui, W Schenkein, D Shringarpure, R Anderson, K Lister, TA Joel, SP TI The effect of proteasome inhibitor with Bortezomib (Velcade (TM)) in B-cell lymphoma cell lines SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 St Bartholomews Hosp, Canc Res UK, Med Oncol Unit, London, England. Millennium Pharmaceut, Cambridge, MA USA. Dana Faber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3361 BP 903A EP 903A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703361 ER PT J AU Shikama, Y Shichishima, T Matsuoka, I Sieff, CA Jubinsky, P Maruyama, Y AF Shikama, Y Shichishima, T Matsuoka, I Sieff, CA Jubinsky, P Maruyama, Y TI A novel mutation in granulocyte-macrophage colony-stimulating factor receptor common beta subunit accumulated in myelodysplastic syndromes abolishes its cell-surface expression and function. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Fukushima Med Univ, Dept Pharmacol, Fukushima, Japan. Fukushima Med Univ, Dept Internal Med 1, Fukushima, Japan. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3397 BP 913A EP 913A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703397 ER PT J AU Liu, TGX Becker, MW Hsu, K Deng, M Clarke, MF Look, AT AF Liu, TGX Becker, MW Hsu, K Deng, M Clarke, MF Look, AT TI Loss of CTNNA1 in MDS and/or AML with del(5q). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Univ Michigan, Div Hematol Oncol, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3401 BP 914A EP 914A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703401 ER PT J AU Gotlib, J Berube, C Ruan, J Growney, J Dugan, K Falkow, R Rosamilia, M Resta, D Cohen, P Fabbro, D Heinrich, M Gilliland, DG Coutre, S AF Gotlib, J Berube, C Ruan, J Growney, J Dugan, K Falkow, R Rosamilia, M Resta, D Cohen, P Fabbro, D Heinrich, M Gilliland, DG Coutre, S TI PKC412, inhibitor of the KIT tyrosine kinase, demonstrates efficacy in mast cell leukemia with the D816V KIT mutation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Novartis Pharm Inc, E Hanover, NJ USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Harvard Univ, Sch Med, Boston, MA USA. Portland VA Med Ctr, Portland, OR USA. RI Heinrich, Michael/C-3727-2013 OI Heinrich, Michael/0000-0003-2611-6303 NR 0 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3420 BP 919A EP 919A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703420 ER PT J AU Tai, YT Catley, LP Podar, K Burger, R Shringapure, R Hideshima, T Chauhan, D Mitsiades, C Ishitsuka, K Hamasaki, M Munshi, NC Anderson, KC AF Tai, YT Catley, LP Podar, K Burger, R Shringapure, R Hideshima, T Chauhan, D Mitsiades, C Ishitsuka, K Hamasaki, M Munshi, NC Anderson, KC TI The role of membrane raft in modulating CD40 signaling, ERK activation and cytokine production in human multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3457 BP 929A EP 929A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703457 ER PT J AU Hideshima, T Hayashi, T Chauhan, D Akiyama, M Richardson, PG Anderson, KC AF Hideshima, T Hayashi, T Chauhan, D Akiyama, M Richardson, PG Anderson, KC TI Biologic sequelae of c-Jun NH2-terminal kinase (JNK) activation in multiple myeloma (MM) cell lines. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3463 BP 930A EP 930A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703463 ER PT J AU Chauhan, D Li, GL Hideshima, T Podar, K Catley, L Shringarpure, R Mitsiades, C Munshi, N Yew, PR Anderson, KC AF Chauhan, D Li, GL Hideshima, T Podar, K Catley, L Shringarpure, R Mitsiades, C Munshi, N Yew, PR Anderson, KC TI Role of ubiquitin-conjugating enzyme CDC34 in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Inst Biotechnol, San Antonio, TX 78285 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3472 BP 932A EP 933A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703472 ER PT J AU Crawford, LJ Morris, TC Chauhan, D Anderson, KC Walker, B Irvine, AE AF Crawford, LJ Morris, TC Chauhan, D Anderson, KC Walker, B Irvine, AE TI Proteasome activity is cell-type dependent. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland. Belfast City Hosp, Belfast BT9 7AD, Antrim, North Ireland. Dana Farber Canc Inst, Boston, MA 02115 USA. RI IRVINE, ALEXANDRA/B-3497-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3475 BP 933A EP 933A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703475 ER PT J AU Chauhan, D Li, GL Hideshima, T Podar, K Catley, L Munshi, N Sporn, MB Anderson, KC AF Chauhan, D Li, GL Hideshima, T Podar, K Catley, L Munshi, N Sporn, MB Anderson, KC TI Bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic apoptosis in multiple myeloma (MM) cells SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03756 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3480 BP 935A EP 935A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703480 ER PT J AU Hamasaki, M Hideshima, T Akiyama, M Hayashi, T Ishitsuka, K Tai, YT Podar, K Munshi, NC Anderson, KC AF Hamasaki, M Hideshima, T Akiyama, M Hayashi, T Ishitsuka, K Tai, YT Podar, K Munshi, NC Anderson, KC TI Atiprimod overcomes conventional drug resistance in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3484 BP 935A EP 936A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703484 ER PT J AU Tai, YT Mitsiades, CS Catley, LP Burger, R Podar, K Shringarpure, R Hideshima, T Chauhan, D Hamasaki, M Ishitsuka, K Richardson, P Munshi, N Treon, S Anderson, K AF Tai, YT Mitsiades, CS Catley, LP Burger, R Podar, K Shringarpure, R Hideshima, T Chauhan, D Hamasaki, M Ishitsuka, K Richardson, P Munshi, N Treon, S Anderson, K TI A chimeric humanized anti-CD40 antibody renders human multiple myeloma (MM) cells refractory to the mitogenic and protective effects of IL-6 SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3482 BP 935A EP 935A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703482 ER PT J AU Chabner, KT Adams, GB Qiu, JH Moskowitz, M Marsters, EM Topulos, G Scadden, DT AF Chabner, KT Adams, GB Qiu, JH Moskowitz, M Marsters, EM Topulos, G Scadden, DT TI Enhanced vascular delivery of primitive hematopoietic cells to bone marrow is insufficient to improve engraftment. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3508 BP 942A EP 942A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703508 ER PT J AU Asavaroengchai, W Sykes, M AF Asavaroengchai, W Sykes, M TI GVHD inhibition by FTY720 is associated with differentially altered accumulation of CD4 and CD8 cells in Peyer's patches, lymph nodes and spleen. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Transplantat Biol Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3533 BP 948A EP 949A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703533 ER PT J AU Hochberg, E Miklos, D Levin, J Beroukhim, R Antin, J Soiffer, R Ritz, J AF Hochberg, E Miklos, D Levin, J Beroukhim, R Antin, J Soiffer, R Ritz, J TI A novel method for the assessment of genetic disparity in stem cell transplant patients and donors using high-density single nucleotide polymorphism (SNP) microarrays. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 3530 BP 948A EP 948A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703530 ER PT J AU Asavaroengchai, W Bronson, RT Sykes, MA Yang, YG AF Asavaroengchai, W Bronson, RT Sykes, MA Yang, YG TI Donor-derived IFN-gamma inhibits GVHD in mice after CD4-depleted allogeneic hematopoietic cell transplantation: An essential role for IFN-gamma in controlling donor CD8 T cell activation, proliferation, and survival. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Transplantat Biol Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3534 BP 949A EP 949A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703534 ER PT J AU Chakraverty, R Buchli, J Zhao, GL Sachs, T Sykes, M AF Chakraverty, R Buchli, J Zhao, GL Sachs, T Sykes, M TI Comparison of donor T-cell activation, expansion and trafficking in freshly irradiated mice and delayed DLI recipients. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Transplant Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3535 BP 949A EP 949A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703535 ER PT J AU Miklos, DB Kim, HT Zorn, E Hochberg, EP Miller, KH Guo, LX Soiffer, RJ Antin, JH Ritz, J AF Miklos, DB Kim, HT Zorn, E Hochberg, EP Miller, KH Guo, LX Soiffer, RJ Antin, JH Ritz, J TI Antibody responses to multiple H-Y minor histocompatibility antigens are induced after allogeneic stem cell transplantation and in normal female donors. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 3537 BP 950A EP 950A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703537 ER PT J AU Soiffer, RJ Kim, HT Hochberg, EP Ho, V Cutler, C Lee, SJ Fisher, DC Alyea, EP Antin, JH AF Soiffer, RJ Kim, HT Hochberg, EP Ho, V Cutler, C Lee, SJ Fisher, DC Alyea, EP Antin, JH TI Preservation of graft-versus-leukemia activity after CD8 depleted allogeneic peripheral blood cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3593 BP 964A EP 965A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703593 ER PT J AU Gribben, JG Sequist, L Zahrieh, D Neuberg, D Alyea, EP Fisher, DC Freedman, AS Schlossman, RL Soiffer, RJ Ritz, J Nadler, LM AF Gribben, JG Sequist, L Zahrieh, D Neuberg, D Alyea, EP Fisher, DC Freedman, AS Schlossman, RL Soiffer, RJ Ritz, J Nadler, LM TI Outcome following autologous or allogeneic stem cell transplantation in chronic lymphocytic leukemia SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2003 VL 102 IS 11 MA 3649 BP 980A EP 981A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703649 ER PT J AU Lloyd-Jones, DM Camargo, CA Allen, LA Giugliano, RP O'Donnell, CJ AF Lloyd-Jones, DM Camargo, CA Allen, LA Giugliano, RP O'Donnell, CJ TI Predictors of long-term mortality after hospitalization for primary unstable angina pectoris and non-ST-elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK STRATIFICATION; CORONARY SYNDROMES; FOLLOW-UP; MANAGEMENT; PROGNOSIS; CLASSIFICATION; ASSOCIATION; GUIDELINES AB Data are sparse regarding long-term outcomes after hospitalization for unstable angina pectoris (UAP) and non-ST-elevation myocardial infarction (NSTEMI), as defined by contemporary criteria. We extended follow-up in a preexisting database of unselected patients with primary UAP and NSTEMI admitted by way of the emergency department from 1991 to 1992. Stepwise Cox models were used to identify multivariate predictors of long-term mortality. There were 275 patients (mean age 66 +/- 12 years, 33% women) who survived to hospital discharge; 134 patients (49%) died during follow-up (median 9.4 years). Significant multivariate predictors of long-term mortality were: age (hazard ratio [HR] per decade 1.7, 95% confidence interval [CI] 1.4 to 1.9); prior MI (HR 1.7, 95% Cl 1.2 to 2.5); diabetes (HR 1.7, 95% CI 1.2 to 2.4); congestive heart failure (HR 2.2, 95% CI 1.5 to 3.4); elevated creatinine (HR 2.5, 95% CI 1.7 to 3.8); elevated leukocyte count (HR 1.7, 95% CI 1.1 to 2.5); systolic blood pressure <120 mm Hg at presentation (HR 2.0, 95% CI 1.1 to 3.6); lack of coronary revascularization during the index hospitalization (HR 2.0, 95% Cl 1.3 to 3.0); and lack of discharge beta-blocker therapy (HR 1.5, 95% CI 1.1 to 2.2). A clinical prediction rule was generated by assigning weighted point scores for the presence of each significant covariate. Long-term mortality increased markedly with each quintile of score; for quintiles 1 to 5, mortality rates were 8.5%, 29.4%, 47.6%, 75.0%, and 91.5%, respectively (p value for trend <0.001). These data are among the first assessments of long-term mortality after hospitalization for primary UAP and NSTEMI, as defined by contemporary guideline criteria. Easily obtained clinical covariates provide excellent prediction of long-term mortality up to 10 years after hospitalization for primary UAP and NSTEMI. (C)2003 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Lloyd-Jones, DM (reprint author), Massachusetts Gen Hosp, Div Cardiol, CIN 064, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 18 TC 20 Z9 20 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2003 VL 92 IS 10 BP 1155 EP 1159 DI 10.1016/j.amjcard.2003.07.022 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 744NM UT WOS:000186638600003 PM 14609588 ER PT J AU Gault, J Hopkins, J Berger, R Drebing, C Logel, J Walton, C Short, M Vianzon, R Olincy, A Ross, RG Adler, LE Freedman, R Leonard, S AF Gault, J Hopkins, J Berger, R Drebing, C Logel, J Walton, C Short, M Vianzon, R Olincy, A Ross, RG Adler, LE Freedman, R Leonard, S TI Comparison of polymorphisms in the alpha 7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; mutation; promoter; nicotinic receptor; sensory processing; auditory gating ID ACETYLCHOLINE-RECEPTOR; LINKAGE DISEQUILIBRIUM; CHROMOSOME-15 LOCUS; MENTAL-ILLNESS; SUBUNIT GENE; CHRNA7; EXPRESSION; SUSCEPTIBILITY; BUNGAROTOXIN; SMOKING AB The hypothesis that the 15q13-15 region of chromosome 15 contains a gene that contributes to the etiology of schizophrenia is supported by multiple genetic linkage studies. The alpha7 neuronal nicotinic acetylcholine receptor (CHRNA7) gene was selected as the best candidate gene in this region for molecular investigation, based on these linkage findings and biological evidence in both human and rodent models. CHRNA7 receptors are decreased in expression in postmortem brain of schizophrenic subjects. A dinucleotide marker, D15S1360, in intron two of the CHRNA7 gene is genetically linked to an auditory gating deficit found in schizophrenics and half of the first-degree relatives of patients. Single strand conformation polymorphism (SSCP) and sequence analyses of DNA from schizophrenic and control individuals identified 33 variants in the coding region and intron/exon borders of the CHRNA7 gene and its partial duplication, dupCHRNA7, common polymorphisms were mapped. Twenty-one variants were found in the exons, but non-synonymous changes were rare. Although the expression of CHRNA7 is decreased in schizophrenia, the general structure of the remaining receptors is likely to be normal. (C) 2003 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. RP Leonard, S (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Box C-268-71,4200 E 9th Ave, Denver, CO 80262 USA. FU NIDA NIH HHS [DA09457, DA12281]; NIMH NIH HHS [MH38321, MH42212] NR 45 TC 62 Z9 67 U1 2 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 15 PY 2003 VL 123B IS 1 BP 39 EP 49 DI 10.1002/ajmg.b.20061 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 735ZU UT WOS:000186145800006 PM 14582144 ER PT J AU Faraone, SV Tsuang, MT AF Faraone, SV Tsuang, MT TI Heterogeneity and the genetics of bipolar disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Editorial Material ID DEFICIT HYPERACTIVITY DISORDER; CARDIO-FACIAL SYNDROME; EARLY ADOLESCENT BIPOLARITY; ALZHEIMERS-DISEASE LOCUS; FAMILIAL RISK ANALYSIS; LA-TOURETTES SYNDROME; INITIAL GENOME SCAN; CONDUCT DISORDER; FOLLOW-UP; TRINUCLEOTIDE REPEAT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Johnson & Johnson Ctr Pediat Psychopathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, WRN 705,55 Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37694]; NIMH NIH HHS [R01MH57934, R01MH43518, R01MH59624, R01MH60485, R13MH59126] NR 111 TC 18 Z9 18 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD NOV 15 PY 2003 VL 123C IS 1 BP 1 EP 9 DI 10.1002/ajmg.c.20017 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 738VR UT WOS:000186309000001 PM 14601031 ER PT J AU Smoller, JW Finn, CT AF Smoller, JW Finn, CT TI Family, twin, and adoption studies of bipolar disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE family studies; twin studies; adoption studies; bipolar disorder; genetic epidemiology ID POPULATION-ASCERTAINED SUBSAMPLES; MANIC-DEPRESSIVE ILLNESS; PILOT SWEDISH TWIN; PANIC DISORDER; EARLY-ONSET; PSYCHIATRIC-DISORDERS; PSYCHOTIC SYMPTOMS; II DISORDER; GENETIC TRANSMISSION; UNIPOLAR DEPRESSION AB Family, twin, and adoption studies have been essential in defining the genetic epidemiology of bipolar disorder over the past several decades. Family studies have documented that first-degree relatives of affected individuals have an excess risk of the disorder, while twin studies (and to a lesser extent, adoption studies) suggest that genes are largely responsible for this familial aggregation. We review these studies, including the magnitude of familial risk and heritability estimates, efforts to identify familial subtypes of bipolar disorder, and the implications of family/genetic data for validating nosologic boundaries. Taken together, these studies indicate that bipolar disorder is phenotypically and genetically complex. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Genet Training Program, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Mood & Anxiety Disorders Outpatient Div, Psychiat Genet Program, Boston, MA 02114 USA. RP Smoller, JW (reprint author), 15 Parkman St,WAC-812, Boston, MA 02114 USA. NR 85 TC 278 Z9 290 U1 5 U2 27 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD NOV 15 PY 2003 VL 123C IS 1 BP 48 EP 58 DI 10.1002/ajmg.c.20013 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 738VR UT WOS:000186309000006 PM 14601036 ER PT J AU Kraveka, JM Li, L Bielawski, J Obeid, LM Ogretmen, B AF Kraveka, JM Li, L Bielawski, J Obeid, LM Ogretmen, B TI Involvement of endogenous ceramide in the inhibition of telomerase activity and induction of morphologic differentiation in response to all-trans-retinoic acid in human neuroblastoma cells SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID EUKARYOTIC STRESS-RESPONSE; HUMAN NEURO-BLASTOMA; CATALYTIC SUBUNIT; N-MYC; REVERSE-TRANSCRIPTASE; SPHINGOLIPID METABOLISM; CRITICAL DETERMINANT; PROTEIN PHOSPHATASE; RNA COMPONENT; EXPRESSION AB In this study, we examined the role of endogenous ceramide in the inhibition of telomerase and induction of morphologic differentiation in response to all-trans-retinoic acid (ATRA) in the SK-N-SH and SK-N-AS human neuroblastoma cell lines. The results showed that ATRA inhibited the activity of telomerase significantly in a time- and dose-dependent manner, as determined by telomere repeat amplification protocol (TRAP). The inhibition of telomerase by ATRA was maximum (about 50-80% of untreated controls) at 5-10 muM for 4-8 days. Treatment of cells with ATRA (5 muM) also resulted in the inhibition of growth by about 30-70% after 4 and 8 days of treatment, respectively, which was measured by trypan blue exclusion method. Measurement of accumulation of endogenous ceramide by high pressure liquid chromatography coupled with mass spectroscopy (LC/MS) showed that treatment of cells with ATRA resulted in increased levels of mainly C24:0 and C24:1 ceramides at days 2, 4, and 8, respectively. Also, treatment of cells with ATRA in the presence of myriocin blocked the accumulation of ceramide significantly, and more importantly, presence of myriocin partially prevented the inhibition of telomerase. Mechanistically, inhibition of telomerase by endogenous ceramide in response to ATRA treatment involves, at least in part, down-regulation of the expression of telomerase reverse transcriptase (hTERT) mRNA, as determined by semi-quantitative RT-PCR, in these cells. In addition, the modulation of telomerase activity by ATRA correlated with the induction of morphologic differentiation, which was also blocked by myriocin, as determined by extension of neurites using phase-contrast microscopy. These results, therefore, reveal an important effect of ATRA on telomerase inhibition and induction of morphologic differentiation in human neuroblastoma cells. These data also demonstrate that endogenous ceramide is one of the upstream regulators of telomerase activity in human neuroblastoma cells in response to ATRA. (C) 2003 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Div Hematol & Oncol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Ogretmen, B (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA 88932]; NCRR NIH HHS [RR 17677-01]; NIA NIH HHS [AG 16583] NR 77 TC 31 Z9 35 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 2003 VL 419 IS 2 BP 110 EP 119 DI 10.1016/j.abb.2003.08.034 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 744CL UT WOS:000186610300003 PM 14592454 ER PT J AU Choy, HA Wang, XP Schotz, MC AF Choy, HA Wang, XP Schotz, MC TI Reduced atherosclerosis in hormone-sensitive lipase transgenic mice overexpressing cholesterol acceptors SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE hormone-sensitive lipase; atherosclerosis; efflux; cholesterol acceptor; macrophage ID LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN A-IV; MACROPHAGE FOAM CELLS; E-DEFICIENT MICE; MOUSE PERITONEAL-MACROPHAGES; ESTER HYDROLYSIS; MESSENGER-RNA; J774 MACROPHAGES; PROTEIN-KINASE; GENE-TRANSFER AB Macrophage-specific overexpression of cholesteryl ester hydrolysis in hormone-sensitive lipase transgenic (HSL Tg) female mice paradoxically increases cholesterol esterification and cholesteryl ester accumulation in macrophages, and thus susceptibility to diet-induced atherosclerosis compared to nontransgenic C57BL/6 mice. The current studies suggest that whereas increased cholesterol uptake could contribute to transgenic foam cell formation, there are no differences in cholesterol synthesis and the expression of cholesterol efflux mediators (ABCA1, ABCG1, apoE, PPARgamma, and LXRalpha) compared to wild-type macrophages. HSL Tg macrophages exhibit twofold greater efflux of cholesterol to apoA-I in vitro, suggesting the potential rate-limiting role of cholesteryl ester hydrolysis in efflux. However, macrophage cholesteryl ester levels appear to depend on the relative efficacy of alternate pathways for free cholesterol in either efflux or re-esterification. Thus, increased atherosclerosis in HSL Tg mice appears to be due to the coupling of the efficient re-esterification of excess free cholesterol to its limited removal mediated by the cholesterol acceptors in these mice. The overexpression of cholesterol acceptors in HSL-apoA-IV double-transgenic mice increases plasma HDL levels and decreases diet-induced atherosclerosis compared to HSL Tg mice, with aortic lesions reduced to sizes in nontransgenic littermates. The results in vivo are consistent with the effective efflux from HSL Tg macrophages supplemented with HDL and apoA-I in vitro, and highlight the importance of cholesterol acceptors in inhibiting atherosclerosis caused by imbalances in the cholesteryl ester cycle. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Schotz, MC (reprint author), Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Lipid Res Lab, Room 312,Bldg 113,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 76 TC 13 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD NOV 15 PY 2003 VL 1634 IS 3 BP 76 EP 85 DI 10.1016/j.bbalip.2003.09.001 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 750JL UT WOS:000186987500003 PM 14643795 ER PT J AU Wright, CI Martis, B McMullin, K Shin, LM Rauch, SL AF Wright, CI Martis, B McMullin, K Shin, LM Rauch, SL TI Amygdala and insular responses to emotionally valenced human faces in small animal specific phobia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anxiety disorder; functional magnetic resonance imaging; human; face perception; emotion; neuroimaging ID OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL BLOOD-FLOW; POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; GLUCOSE METABOLIC RATES; BASE-LINE CONDITIONS; FACIAL EXPRESSIONS; SYMPTOM PROVOCATION; SOCIAL PHOBIA; HUMAN BRAIN AB Background: Contemporary neurobiological models suggest that the amygdala plays an important role in the pathophysiology of anxiety disorders. However, it is not clear to what extent this concept applies across anxiety disorders. Several studies have examined brain function in specific phobias but did not demonstrate amygdala responses or use specific probes of the amygdala. Methods: Ten subjects with specific small animal phobia and 10 matched control subjects were studied with functional magnetic resonance imaging. Subjects viewed emotionally expressive and neutral faces, and amygdala blood oxygenation level dependent responses from each group were compared. Results: There was a significant response to the fearful versus neutral faces in the amygdala across both groups but no diagnosis X condition interaction. Post hoc analysis of the whole brain revealed a significantly greater response to the fearful versus neutral faces in the right insular cortex of the specific phobia group than in the control group. Conclusions: Amygdala hyperresponsivity to emotional faces was not observed in subjects with small animal specific phobia, in contrast to findings in other anxiety disorders (e.g., posttraumatic stress disorder). This suggests a restricted role for the amygdala in specific phobia. The insular hyperresponsivity to fearful versus neutral faces in the subjects with specific phobias warrants further study. Biol Psychiatry 2003;54:1067-1076 (C) 2003 Society of Biological Psychiatry C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Wright, CI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Grp, 13th St,Bldg 149,CNY-9119, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH60219, MH64806] NR 78 TC 99 Z9 100 U1 5 U2 14 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 NOV 15 PY 2003 VL 54 IS 10 BP 1067 EP 1076 DI 10.1016/S0006-3223(03)00548-1 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 742RC UT WOS:000186531000013 PM 14625149 ER PT J AU Prchal, JF Prchal, JT AF Prchal, JF Prchal, JT TI A specific test for polycythemia vera? SO BLOOD LA English DT Editorial Material C1 McGill Univ, Montreal, PQ H3A 2T5, Canada. Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. RP Prchal, JF (reprint author), McGill Univ, Montreal, PQ H3A 2T5, Canada. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2003 VL 102 IS 10 BP 3464 EP 3464 DI 10.1182/blood-2003-09-3089 PG 1 WC Hematology SC Hematology GA 741XT UT WOS:000186486200005 ER PT J AU Boros, LG Steinkamp, MP Fleming, JC Lee, WNP Cascante, M Neufeld, EJ AF Boros, LG Steinkamp, MP Fleming, JC Lee, WNP Cascante, M Neufeld, EJ TI Defective RNA ribose synthesis in fibroblasts from patients with thiamine-responsive megaloblastic anemia (TRMA) SO BLOOD LA English DT Article ID METABOLIC CONTROL ANALYSIS; HUMAN HEPATOMA-CELLS; CARBOHYDRATE METABOLISM; MASS ISOTOPOMER; DRUG DISCOVERY; TRANSPORTER; PROLIFERATION; APOPTOSIS; PATHWAYS; GLUCOSE AB Fibroblasts from patients with thiamine-responsive megaloblastic anemia (TRMA) syndrome with diabetes and deafness undergo apoptotic cell death in the absence of supplemental thiamine in their cultures. The basis of megaloblastosis in these patients has not been determined. Here we use the stable [1,2-C-13(2)]glucose isotope-based dynamic metabolic profiling technique to demonstrate that defective high-affinity thiamine transport primarily affects the synthesis of nucleic acid ribose via the nonoxidative branch of the pentose cycle. RNA ribose isolated from TRMA fibroblasts in thiamine-depleted cultures shows a time-dependent decrease in the fraction of ribose derived via transketolase, a thiamine-dependent enzyme in the pentose cycle. The fractional rate of de novo ribose synthesis from glucose is decreased several fold 2 to 4 days after removal of thiamine from the culture medium. No such metabolic changes are observed in wild-type fibroblasts or in TRMA mutant cells in thiamine-containing medium. Fluxes through glyco-lysis are similar in TRMA versus control fibroblasts in the pentose and TCA cycles. We conclude that reduced nucleic acid production through impaired transketolase catalysis is the underlying biochemical disturbance that likely induces cell cycle arrest or apoptosis in bone marrow cells and leads to the TRMA syndrome in patients with defective high-affinity thiamine transport. (C) 2003 by The American Society of Hematology. C1 Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Stable Isotope Res Lab, Sch Med,Res & Educ Inst, Torrance, CA 90502 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. RP Boros, LG (reprint author), Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Stable Isotope Res Lab, Sch Med,Res & Educ Inst, 1124 W Carson St,RB1, Torrance, CA 90502 USA. RI Neufeld, Ellis/F-9331-2011; OI Steinkamp, Mara/0000-0003-1226-9325; CASCANTE, MARTA/0000-0002-2062-4633 FU NCI NIH HHS [P01-CA42710]; NCRR NIH HHS [M01-RR00045]; NHLBI NIH HHS [K24 HLK24HL004184, R01 HL66182-01A1] NR 27 TC 37 Z9 37 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2003 VL 102 IS 10 BP 3556 EP 3561 DI 10.1182/blood-2003-05-1537 PG 6 WC Hematology SC Hematology GA 741XT UT WOS:000186486200025 PM 12893755 ER PT J AU Richards, MK Liu, FL Iwasaki, H Akashi, K Link, DC AF Richards, MK Liu, FL Iwasaki, H Akashi, K Link, DC TI Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway SO BLOOD LA English DT Article ID RECEPTOR-DEFICIENT MICE; HEMATOPOIETIC STEM-CELLS; BONE-MARROW; G-CSF; IN-VIVO; MYELODYSPLASTIC SYNDROMES; LINEAGE COMMITMENT; IRRADIATED MICE; SELF-RENEWAL; DIFFERENTIATION AB Granulocyte colony-stimulating factor (G-CSF) is the principal cytokine regulating granulopoiesis. G-CSF receptor-deficient mice (G-CSFR-/-) are neutropenic but have only a modest reduction of committed myeloid progenitors. Since it is likely that compensatory mechanisms are induced by the severe neutropenia present in G-CSFR-/- mice, a competitive repopulation assay was performed. These data show that under basal conditions, G-CSF drives nearly all of granulopoiesis through multiple mechanisms. Most importantly, G-CSFR signals regulate the production and/or maintenance of committed-myeloid progenitors. Surprisingly, G-CSFR signals also play a significant role in the regulation of primitive multipotential progenitors in vivo. The contribution of G-CSFR-/- cells to the hematopoietic stem cell compartment is modestly reduced. Moreover, a marked decrease in the contribution of G-CSFR-/- cells to other progenitors in the myeloid pathway, including erythroid and megakaryocytic progenitors, is observed. In contrast, relative to the hematopoietic stem cell compartment, the contribution of G-CSFR-/- cells to the lymphoid lineages is increased. These data suggest that G-CSFR signals may play a role in directing the commitment of primitive hematopoietic progenitors to the common myeloid lineage. Thus, regulation of G-CSF levels may provide a mechanism for directing primitive hematopoietic progenitors into the common myeloid lineage in response to environmental stresses. (C) 2003 by The American Society of Hematology. C1 Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Link, DC (reprint author), Washington Univ, Sch Med, Dept Med, Div Oncol, 660 S Euclid Ave,Campus Box 8007, St Louis, MO 63110 USA. FU NICHD NIH HHS [5T32HD0749904] NR 36 TC 63 Z9 66 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2003 VL 102 IS 10 BP 3562 EP 3568 DI 10.1182/blood-2003-02-0593 PG 7 WC Hematology SC Hematology GA 741XT UT WOS:000186486200026 PM 12893769 ER PT J AU Ni, HY Papalia, JM Degen, JL Wagner, DD AF Ni, HY Papalia, JM Degen, JL Wagner, DD TI Control of thrombus embolization and fibronectin internalization by integrin alpha IIb beta 3 engagement of the fibrinogen gamma chain SO BLOOD LA English DT Article ID VON-WILLEBRAND-FACTOR; PLATELET-AGGREGATION; MICE LACKING; FLOW CONDITIONS; MODEL; DISTINCT; PLASMA; HEMOSTASIS; AFIBRINOGENEMIA; THROMBASTHENIA AB Fibrin(ogen) deficiency (Fg(-/-)) was shown previously to be compatible with rapid thrombus growth within injured arterioles, but platelet fibronectin content was increased and newly formed thrombi were unstable. To further define the role of fibrin(ogen) in thrombus formation and stabilization, platelet biology was examined in mice expressing a form of fibrinogen that clots normally but lacks the gamma chain C-terminal binding site for alphallbbeta3 (FggammaDelta5). Thrombus growth within the arterioles of FggammaDelta5 mice appeared faster than in wild-type mice despite a far greater emboli formation. Unlike Fg(-/-) mice, the emboli were relatively small and released from the top of thrombi, rather than by fracture at the vessel wall. The fibronectin content in FggammaDelta5 platelets was also dramatically increased through a beta3 integrin-dependent mechanism. The following has been concluded: (1) Fibrin formation contributes to, but is not sufficient for, the stabilization of arterial thrombi. Platelet receptor engagement of the C-terminal of the Fggamma chain contributes to the stable incorporation of platelets into thrombi. (2) Alternative ligands to fibrinogen can support efficient thrombus growth. (3) Fibrinogen is internalized through alphallbbeta3 engagement of the fibrinogen gamma chain element, and this interaction secondarily controls the fibronectin content of platelets. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. RP Ni, HY (reprint author), Univ Toronto, St Michaels Hosp, Canadian Blood Serv, 30 Bond St,Rm 2-006,Bond Wing, Toronto, ON M5B 1W8, Canada. OI Ni, Heyu/0000-0002-7621-2945 FU NHLBI NIH HHS [P01 HL056949, R37HL41002, P01HL56949, R37 HL041002, R01HL63194] NR 38 TC 54 Z9 56 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2003 VL 102 IS 10 BP 3609 EP 3614 DI 10.1182/blood-2003-03-0850 PG 6 WC Hematology SC Hematology GA 741XT UT WOS:000186486200033 PM 12855554 ER PT J AU Ned, RM Swat, W Andrews, NC AF Ned, RM Swat, W Andrews, NC TI Transferrin receptor 1 is differentially required in lymphocyte development SO BLOOD LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; HUMAN ERYTHROID PRECURSORS; B-CELL DEVELOPMENT; IRON UPTAKE; HYPOTRANSFERRINEMIC MICE; INVITRO STIMULATION; MOUSE LYMPHOCYTES; RAT HEPATOCYTES; FERRITIN UPTAKE; BONE-MARROW AB Transferrin receptor (TfR) facilitates cellular iron uptake by mediating endocytosis of its ligand, iron-loaded transferrin. Although TfR is widely believed to be important for iron acquisition by all mammalian cells, direct experimental evidence is lacking. We have previously shown that mouse embryos homozygous for a disrupted transferrin receptor allele (TfR-/-) die of anemia before embryonic day 12.5, although most other embryonic tissues appear to be developing normally. Here, we have investigated the importance of TfR postnatally, by using TfR-/- embryonic stem cells to produce chimeric animals. We find that TfR-/- embryonic stem cells give rise to most tissues and organs, but do not contribute to hematopoietic tissues on a wild-type C57BL/6J background, indicating that both adult erythropoiesis and lymphopoiesis require TfR. On an Immunodeficient RAG2(-/-) background, TfR-/- B-cell development proceeds at least to the IgM(+) stage, although significantly fewer IgM(+) cells are present in peripheral lymphoid organs. Conversely, T cells lacking TfR are arrested very early in their development, at the CD4(-)8(-)3(-) stage. These results indicate that TfR is necessary for the normal maturation of thymocytes, but that B-cell development is less severely affected by the absence of TfR. (C) 2003 by The American Society of Hematology. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Div Med Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Dept Pathol, St Louis, MO 63130 USA. Washington Univ, Dept Immunol, St Louis, MO 63130 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Andrews, NC (reprint author), Childrens Hosp, Div Hematol Oncol, Enders 720,300 Longwood Ave, Boston, MA 02115 USA. RI Ned, Renee/D-3746-2009; OI Andrews, Nancy/0000-0003-0243-4462 FU NHLBI NIH HHS [R01 HL51057]; NICHD NIH HHS [P30 HD18655] NR 56 TC 35 Z9 38 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 NOV 15 PY 2003 VL 102 IS 10 BP 3711 EP 3718 DI 10.1182/blood-2003-04-1086 PG 8 WC Hematology SC Hematology GA 741XT UT WOS:000186486200047 PM 12881306 ER PT J AU Michaelson, JS Satija, S Kopans, D Moore, R Silverstein, M Comegno, A Hughes, K Taghian, A Powell, S Smith, B AF Michaelson, JS Satija, S Kopans, D Moore, R Silverstein, M Comegno, A Hughes, K Taghian, A Powell, S Smith, B TI Gauging the impact of breast carcinoma screening in terms of tumor size and death rate SO CANCER LA English DT Article DE breast carcinoma; survival; tumor size; mammography; screening ID RELIABLE SUPPORTING EVIDENCE; RANDOMIZED TRIALS; NATURAL-HISTORY; FOLLOW-UP; IN-SITU; CANCER; MAMMOGRAPHY; WOMEN; AGE; MORTALITY AB BACKGROUND. While the question of whether the trials of breast cancer screening have resulted in a reduction in breast cancer death has been the subject of much 4,5 scrutiny, there has been less attention to the reduction in tumor size achieved by screening. METHODS. Size data for invasive breast tumors were assembled from a variety of 2 sources. The health consequences that can be expected from finding tumors of various sizes were determined using a recently developed mathematical method for relating tumor size to death rate. RESULTS. First, in both the Swedish two-country trial and at the NIGH Breast Imaging Division, the sizes of the invasive breast cancers in the screening population (those masses seen at screening together with those found as palpable masses after screening examinations) were sufficiently smaller than the cancers found among women who had not used screening to have lead to considerable reductions in death. Second, the lack of reduction in death rates detected in both Canadian National Breast Screening Studies could be ascribed to the small reductions in tumor size achieved in these studies. Third, radiographic density had a small effect, whereas age had a negligible effect, on the capacity of mammographic screening to find breast carcinomas at smaller, and thus less lethal, sizes. 4 CONCLUSIONS. Prompt attendance at annual mammographic screening offers the potential to reduce tumor size and, presumably, breast carcinoma death, in 5 women of all ages and density groups. (C) 2003 Arnerican Cancer Society. C1 Massachusetts Gen Hosp, Dept Pathol, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Univ So Calif, Norris Canc Ctr, Harold E & Henrietta C Lee Breast Ctr, Los Angeles, CA 90089 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Michaelson, JS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Surg Oncol, Cox Bldg Room 626,100 Blossom St, Boston, MA 02114 USA. OI Hughes, Kevin/0000-0003-4084-6484 NR 46 TC 38 Z9 41 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2003 VL 98 IS 10 BP 2114 EP 2124 DI 10.1002/cncr.11766 PG 11 WC Oncology SC Oncology GA 740DY UT WOS:000186387800006 PM 14601080 ER PT J AU Michaelson, JS Silverstein, M Sgroi, D Cheongsiatmoy, JA Taghian, A Powell, S Hughes, K Comegno, A Tanabe, KK Smith, B AF Michaelson, JS Silverstein, M Sgroi, D Cheongsiatmoy, JA Taghian, A Powell, S Hughes, K Comegno, A Tanabe, KK Smith, B TI The effect of tumor size and lymph node status on breast carcinoma lethality SO CANCER LA English DT Article DE breast carcinoma; risk of death; tumor size; lymph node status ID PROGNOSTIC MARKERS; FOLLOW-UP; CANCER; SURVIVAL AB BACKGROUND. It has long been known that both tumor size and the presence of malignant disease in the regional lymph nodes are indicators Of Outcome for patients with invasive breast carcinoma; however, the way in which these two characteristics could be integrated into an overall assessment of prognosis has not been obvious. METHODS. Kaplan-Meier survival estimates (15 years) according to tumor size and lymph node status were obtained for women with invasive breast carcinoma who were observed at the University of Southern California/Van Nuys Breast Center (Van Nuys, California) or at Massachusetts General Hospital (Boston, Massachusetts). RESULTS. To isolate the individual contributions to death made by tumor size and lymph node status, data were sorted according to both of these variables. For women with turners of equivalent size, lethality increased with increasing number of positive lymph nodes, such that there was an extra approximate to6% chance of death associated with each positive lymph node. For women with equivalent lvmph node status, turner size was associated with increased lethality, such that each millimeter of tumor diameter was associated with an additional approximate to1% chance of death. The overall lethality was equal to the sum of the contribution from lvmph node status and the contribution from tumor size, and this finding led to the creation of a new technique (the Size+Nodes method) for predicting outcome. CONCLUSIONS. The Size+Nodes method was shown to be capable of accurately estimating the risk of death due to invasive breast carcinoma from information on the size of the primary tumor and the number of positive lymph nodes. In addition, this method was used to stratify women into groups according to breast carcinoma lethality. In contrast, classification of women according to lymph node positivity, T status, or disease stage created groups with wide and overlapping levels of lethality. (C) 2003 American Cancer Society. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ So Calif, Keck Sch Med, Dept Surg, Los Angeles, CA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Michaelson, JS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Cox Bldg Room 626,100 Blosson St, Boston, MA 02114 USA. OI Hughes, Kevin/0000-0003-4084-6484 NR 17 TC 75 Z9 78 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2003 VL 98 IS 10 BP 2133 EP 2143 DI 10.1002/cncr.11765 PG 11 WC Oncology SC Oncology GA 740DY UT WOS:000186387800008 PM 14601082 ER PT J AU Smith, MR AF Smith, MR TI Antitumor activity of bisphosphonates SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 4 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2003 VL 9 IS 15 BP 5433 EP 5434 PG 2 WC Oncology SC Oncology GA 750TM UT WOS:000187014200001 PM 14654520 ER PT J AU Kirsch, DG Hochberg, FH AF Kirsch, DG Hochberg, FH TI Targeting HER2 in brain metastases from breast cancer SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; SURVIVAL; PROTEIN; CHEMOTHERAPY; INHIBITOR; THERAPY; WOMEN C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Hochberg, FH (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, 100 Blossom St,Cox 315, Boston, MA 02114 USA. NR 13 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2003 VL 9 IS 15 BP 5435 EP 5436 PG 2 WC Oncology SC Oncology GA 750TM UT WOS:000187014200002 PM 14654521 ER PT J AU Gorlick, R Anderson, P Andrulis, I Arndt, C Beardsley, GP Bernstein, M Bridge, J Cheung, NK Dome, JS Ebb, D Gardner, T Gebhardt, M Grier, H Hansen, M Healey, J Helman, L Hock, J Houghton, J Houghton, P Huvos, A Khanna, C Kieran, M Kleinerman, E Ladanyi, M Lau, C Malkin, D Marina, N Meltzer, P Meyers, P Schofield, D Schwartz, C Smith, MA Toretsky, J Tsokos, M Wexler, L Wigginton, J Withrow, S Schoenfeldt, M Anderson, B AF Gorlick, R Anderson, P Andrulis, I Arndt, C Beardsley, GP Bernstein, M Bridge, J Cheung, NK Dome, JS Ebb, D Gardner, T Gebhardt, M Grier, H Hansen, M Healey, J Helman, L Hock, J Houghton, J Houghton, P Huvos, A Khanna, C Kieran, M Kleinerman, E Ladanyi, M Lau, C Malkin, D Marina, N Meltzer, P Meyers, P Schofield, D Schwartz, C Smith, MA Toretsky, J Tsokos, M Wexler, L Wigginton, J Withrow, S Schoenfeldt, M Anderson, B TI Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: Meeting summary SO CLINICAL CANCER RESEARCH LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; OSTEOSARCOMA LUNG METASTASES; SOFT-TISSUE SARCOMAS; P-GLYCOPROTEIN EXPRESSION; PARATHYROID-HORMONE 1-34; FAS-MEDIATED APOPTOSIS; MURINE OSTEOSARCOMA; GENE-EXPRESSION; CELL-LINES; CANINE OSTEOSARCOMA AB Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants. C1 NCI, Clin Invest Branch, Pediat Sect, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Rochester, MN USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. Yale Univ, Sch Med, New Haven, CT USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Univ Nebraska, Med Ctr, Omaha, NE USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Indiana Univ, Med Ctr, Indianapolis, IN 46202 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Connecticut, Ctr Hlth Sci, Farmington, CT USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. MD Anderson Canc Ctr, Houston, TX USA. Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Childrens Hosp, Los Angeles, CA 90027 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Colorado State Univ, Coll Vet Med & Biol Sci, Ft Collins, CO 80523 USA. EMMES Corp, Rockville, MD USA. RP Anderson, B (reprint author), NCI, Clin Invest Branch, Pediat Sect, Canc Therapy Evaluat Program, 6130 Execut Blvd,EPN 741, Rockville, MD 20852 USA. EM AndersonB@CTEP.NCI.NIH.gov RI Andrulis, Irene/E-7267-2013; OI Hock, Janet/0000-0001-8873-2545; Kieran, Mark/0000-0003-2184-7692 NR 126 TC 112 Z9 120 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2003 VL 9 IS 15 BP 5442 EP 5453 PG 12 WC Oncology SC Oncology GA 750TM UT WOS:000187014200004 PM 14654523 ER PT J AU O'Farrell, AM Foran, JM Fiedler, W Serve, H Paquette, RL Cooper, MA Yuen, HA Louie, SG Kim, H Nicholas, S Heinrich, MC Berdel, WE Bello, C Jacobs, M Scigalla, P Manning, WC Kelsey, S Cherrington, JM AF O'Farrell, AM Foran, JM Fiedler, W Serve, H Paquette, RL Cooper, MA Yuen, HA Louie, SG Kim, H Nicholas, S Heinrich, MC Berdel, WE Bello, C Jacobs, M Scigalla, P Manning, WC Kelsey, S Cherrington, JM TI An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; INTERNAL TANDEM DUPLICATION; GROWTH-FACTOR; CONSTITUTIVE ACTIVATION; CELL-GROWTH; MAP KINASE; RISK GROUP; C-KIT; MUTATIONS; DISEASE AB Purpose: Obtaining direct and rapid proof of molecular activity in early clinical trials is critical for optimal clinical development of novel targeted therapies. SU11248 is an oral multitargeted kinase inhibitor with selectivity for fms-related tyrosine kinase 3/Flk2 (FLT3), platelet-derived growth factor receptor alpha/beta, vascular endothelial growth factor receptor 1/2, and KIT receptor tyrosine kinases. FLT3 is a promising candidate for targeted therapy in acute myeloid leukemia (AML), because activating mutations occur in up to 30% of patients. We conducted an innovative single-dose clinical study with a primary objective to demonstrate inhibition of FLT3 phosphorylation by SU11248 in AML. Experimental Design: Twenty-nine AML patients each received a single dose of SU11248, escalated from 50 to 350 mg, in increments of 50 mg and cohorts of three to six patients. FLT3 phosphorylation and plasma pharmacokinetics were evaluated at seven time points over 48 h after SU11248 administration, and FLT3 genotype was deter-mined. Study drug-related adverse events occurred in 31% of patients, mainly grade 1 or 2 diarrhea and nausea, at higher dose levels. Results: Inhibition of FLT3 phosphorylation was apparent in 50% of FLT3-wild-type (WT) patients and in 100% of FLT3-mutant patients. FLT3 internal tandem duplication (ITD) mutants showed increased sensitivity relative to FLT3-WT, consistent with preclinical predictions. The primary end point, strong inhibition of FLT3 phosphorylation in >50% patients, was reached in 200 mg and higher dose cohorts. Downstream signaling pathways were also inhibited; signal transducer and activator of transcription 5 (STAT5) was reduced primarily in internal tandem duplication patients and at late time points in FLT3-WT patients, whereas extracellular signal-regulated kinase (ERK) activity was reduced in the majority of patients, independent of FLT3 inhibition. Conclusions: This novel translational study bridges preclinical models to the patient setting and provides the first evidence of anti-FLT3 activity in patients. Proof of target inhibition accomplishes a crucial milestone in the development of novel oncology therapeutics. C1 SUGEN Inc, San Francisco, CA USA. Univ Alabama, Birmingham, AL USA. Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. Univ Klinikum Munster, Munster, Germany. Community Canc Care Inc, Indianapolis, IN USA. Univ Calif Los Angeles, Stem Cell Serv, Los Angeles, CA 90024 USA. Oregon Hlth & Sci Canc Inst, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Pharmacia Corp, Bedminster, NJ USA. RP O'Farrell, AM (reprint author), 844 Fremont St 4, Menlo Pk, CA 94025 USA. NR 34 TC 215 Z9 225 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2003 VL 9 IS 15 BP 5465 EP 5476 PG 12 WC Oncology SC Oncology GA 750TM UT WOS:000187014200006 PM 14654525 ER PT J AU Znati, CA Rosenstein, M McKee, TD Brown, E Turner, D Bloomer, WD Watkins, S Jain, RK Boucher, Y AF Znati, CA Rosenstein, M McKee, TD Brown, E Turner, D Bloomer, WD Watkins, S Jain, RK Boucher, Y TI Irradiation reduces interstitial fluid transport and increases the collagen content in tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; SOLID TUMORS; MAMMARY-GLAND; RADIATION; PRESSURE; FIBROSIS; CONVECTION; EXPRESSION; DIFFUSION AB Purpose: We have shown that the interstitial diffusion of large molecules is significantly hindered in tumors with high collagen levels. Because large therapeutic agents (e.g., monoclonal antibodies and viral vectors) will be combined with radiation or chemotherapy, it is significant to determine how cytotoxic therapies modify the transport and composition of the interstitial space in tumors. To test the hypothesis that radiation alters tumor interstitial transport, we measured tumor hydraulic conductivity (K) and hyaluronan and collagen type I levels after irradiation. Experimental Design: K and the quantification of interstitial matrix components were determined in sections of s.c. implants of the human colon adenocarcinoma LS174T. K was measured on days 1 and 5 after 10 Gy of irradiation or on day 5 after 30 Gy of irradiation. Results: Compared with control tumors, K decreased by approximately 12-fold after 10 or 30 Gy of irradiation on day 5. At 24 h after irradiation with 10 Gy, the decrease in K was not significant. Five days after 10 and 30 Gy of irradiation, the decrease in K was associated with significantly higher levels of collagen type I. The collagen type I content was not changed 24 h after irradiation with 10 Gy. Irradiation did not significantly increase hyaluronan levels in LS174T tumors. Conclusions: After irradiation, the decrease in K and increase in collagen type I levels could significantly hinder the convective movement and diffusion of large therapeutic agents in tumors. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cell Biol & Physiol, Boston, MA 02114 USA. Carnegie Mellon Univ, Dept Chem Engn, Pittsburgh, PA 15213 USA. Evanston NW Healthcare, Dept Radiat Med, Evanston, IL USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. RP Boucher, Y (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Cox 7, Boston, MA 02114 USA. OI McKee, Trevor/0000-0002-2195-6146 FU NCI NIH HHS [P01-CA-80124, R35-CA56591] NR 28 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2003 VL 9 IS 15 BP 5508 EP 5513 PG 6 WC Oncology SC Oncology GA 750TM UT WOS:000187014200011 PM 14654530 ER PT J AU LaRocque, RC Katz, JT Perruzzi, P Baden, LR AF LaRocque, RC Katz, JT Perruzzi, P Baden, LR TI The utility of sputum induction for diagnosis of Pneumocystis pneumonia in immunocompromised patients without human immunodeficiency virus SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; CARINII PNEUMONIA; PULMONARY-DISEASE; BRONCHOSCOPY; AIDS AB Sputum induction for the diagnosis of Pneumocystis pneumonia (PCP) is widely used for patients with acquired immunodeficiency syndrome (AIDS), but its utility for patients with other forms of immunocompromise is less well defined. Immunocompromised patients with PCP who do not have human immunodeficiency virus (HIV) infection have a lower burden of organisms, and sputum induction may consequently have lower diagnostic yield in these patients. However, this retrospective review of the experience at a tertiary referral center suggests that sputum induction has clinical utility for diagnosing PCP in immunocompromised patients without HIV infection. C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst,Sch Med, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst,Sch Med, Div Pulm, Boston, MA 02115 USA. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM rclarocque@partners.org NR 13 TC 14 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2003 VL 37 IS 10 BP 1380 EP 1383 DI 10.1086/379071 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 737HN UT WOS:000186224500015 PM 14583873 ER PT J AU Mulholland, NM King, IFG Kingston, RE AF Mulholland, NM King, IFG Kingston, RE TI Regulation of Polycomb roup complexes by the sequence-specific DNA binding proteins Zeste and GAGA SO GENES & DEVELOPMENT LA English DT Article ID DROSOPHILA BITHORAX COMPLEX; RESPONSE ELEMENTS; GENE-REGULATION; HOMEOTIC GENE; IN-VITRO; REPRESSION; TRANSVECTION; MAINTENANCE; PROMOTER; ULTRABITHORAX AB Repression and activation of the expression of homeotic genes are maintained by proteins encoded by the Polycomb group (PcG) and trithorax group (trxG) genes. Complexes formed by these proteins are targeted by PcG or trxG response elements (PREs/TREs), which share binding sites. for several of the same factors. GAGA factor and Zeste hind specifically to PREs/TREs and have been shown to act as both activators and repressors. We have used purified proteins and complexes reconstituted from recombinant subunits to characterize the effects of GAGA and Zeste proteins on PcG function using a defined in vitro system. Zeste directly associates with the PRC1 core,complex (PCC) and enhances the inhibitory activity of this complex on all templates, with a preference for templates with Zeste binding sites. GAGA does not stably associate with PCC, but nucleosomal templates bound by GAGA are more efficiently bound and more efficiently inhibited by PCC. Thus Zeste and GAGA factor use distinct means to increase repression mediated by PRC1. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 33 TC 46 Z9 48 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 2003 VL 17 IS 22 BP 2741 EP 2746 DI 10.1101/gad.1143303 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 746FP UT WOS:000186736600002 PM 14630938 ER PT J AU Kuban, DA Thames, HD Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL AF Kuban, DA Thames, HD Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL TI Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 06-10, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Soc Therapeut Radiol & Oncol DE prostate cancer; radiotherapy; multi-institutional analysis; long-term outcome ID RADICAL PROSTATECTOMY; BIOCHEMICAL FAILURE; RADIATION-THERAPY; CONFORMAL RADIOTHERAPY; AMERICAN SOCIETY; ADENOCARCINOMA; IRRADIATION AB Purpose: To report the long-term outcome for patients with Stage T1-T2 adenocarcinoma of the prostate definitively irradiated in the prostate-specific antigen (PSA) era. Methods and Materials: Nine institutions combined data on 4839 patients with Stage T1b, T1c, and T2 adenocarcinoma of the prostate who had a pretreatment PSA level and had received greater than or equal to60 Gy as definitive external beam radiotherapy. No patient had hormonal therapy before treatment failure. The median follow-up was 6.3 years. The end point for outcome analysis was PSA disease-free survival at 5 and 8 years after therapy using the American Society for Therapeutic Radiology and Oncology (ASTRO) failure definition. Results: The PSA disease-free survival rate for the entire group of patients was 59% at 5 years and 53% at 8 years after treatment. For patients who had received greater than or equal to70 Gy, these percentages were 61% and 55%. Of the 4839 patients, 1582 had failure by the PSA criteria, 416 had local failure, and 329 had distant failure. The greatest risk of failure was at 1.5-3.5 years after treatment. The failure rate was 3.5-4.5% annually after 5 years, except in patients with Gleason score 8-10 tumors for whom it was 6%. In multivariate analysis for biochemical failure, pretreatment PSA, Gleason score, radiation dose, tumor stage, and treatment year were all significant prognostic factors. The length of follow-up and the effect of backdating as required by the ASTRO failure definition also significantly affected the outcome results. Dose effects were most significant in the intermediate-risk group and to a lesser degree in the high-risk group. No dose effect was seen at 70 or 72 Gy in the low-risk group. Conclusion: As follow-up lengthens and outcome data accumulate in the PSA era, we continue to evaluate the efficacy and durability of radiotherapy as definitive therapy for early-stage prostate cancer. Similar studies with higher doses and more contemporary techniques will be necessary to explore more fully the potential of this therapeutic modality. (C) 2003 Elsevier Inc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. William Beaumont Hosp, Dept Radiat Oncol, Detroit, MI USA. Washington Univ, Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO USA. Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Kuban, DA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Box 97, Houston, TX 77030 USA. NR 21 TC 176 Z9 179 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2003 VL 57 IS 4 BP 915 EP 928 DI 10.1016/S0360-3016(03)00632-1 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 738NB UT WOS:000186293800004 PM 14575822 ER PT J AU Thames, H Kuban, D Levy, L Horwitz, EM Kupelian, P Martinez, A Michalski, J Pisansky, T Sandler, H Shipley, W Zelefsky, M Zietman, A AF Thames, H Kuban, D Levy, L Horwitz, EM Kupelian, P Martinez, A Michalski, J Pisansky, T Sandler, H Shipley, W Zelefsky, M Zietman, A TI Comparison of alternative biochemical failure definitions' based on clinical outcome in 4839 prostate cancer patients treated by external beam radiotherapy between 1986 and 1995 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 06-10, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Soc Therapeut Radiol & Oncol DE prostate cancer; radiation; prostate-specific antigen; surrogate end point ID RADIATION-THERAPY; AMERICAN SOCIETY; RADIOLOGY AB Purpose: To assess the merit of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure after external beam radiotherapy for prostate cancer by testing alternative prostate-specific antigen (PSA) failure definitions against the "gold standard" of clinical failure and to study the effect of backdating the time of failure. Methods and Materials: Nine participating institutions agreed to submit follow-up results for all patients with clinically localized prostatic cancer (Stage T1b, T1c, T2, N0M0) treated between 1986 and 1995 by external beam radiotherapy only, to doses of greater than or equal to60 Gy, with no androgen deprivation before treatment. A total of 4839 men met the study criteria, with a median follow-up time of 6.3 years. The prediction of clinical failure by 102 definitions of biochemical failure was assessed using various quantitative measures. Results: Four definitions were superior as measured by the sensitivity, specificity, positive and negative predictive values, and hazard of clinical failure after biochemical failure: two rises of at least 0.5 ng/mL backdated, PSA level at or greater than the absolute nadir plus 2 ng/mL at the call date, and PSA level at or greater than the current nadir plus 2 or 3 ng/mL at the call date. The absolute nadir was the lowest measured PSA level during all of follow-up, and the current nadir was the lowest PSA measured previous to a particular PSA measurement during follow-up. With the possible exception of patients in the low-risk group, the likelihood of ultimate clinical failure decreased as the time of biochemical failure increased. Failure definitions based on PSA levels >0.2 or 0.5 ng/mL were inferior to other definitions. Backdating the failure time introduced bias into the estimate of freedom from biochemical failure, which was increasingly overestimated at shorter median follow-up times. This bias can be circumvented either by using a failure definition based on the call date or by backdating the censoring times of patients with one or two rises who could potentially have failure at a future (unobserved) time. A short follow-up time as such does not result in bias unless the failures are backdated; in the absence of backdating, it is the precision of failure-free survival that is increasingly compromised as the follow-up time is reduced. Conclusion: The ASTRO failure definition ended the confusion resulting from different failure definitions that had been in use, and it did so accurately enough that it is probably not necessary to recalculate previously published results. Nevertheless, for the current pooled analysis of outcome in 4839 men with a 6.3-year median follow-up, other definitions of biochemical failure were superior as assessed by various quantitative measures of concordance of biochemical and ultimate clinical failure. An additional disadvantage of the ASTRO definition is the bias introduced by backdating failures, as well as the necessarily retrospective nature of its application. Some "current" definitions, but not those based on the PSA level rising above a fixed threshold, have significantly higher sensitivity and specificity, do not lead to biased estimations of biochemical disease-free survival, and are directly applicable during patient counseling. These are all issues that would play a role in replacing the ASTRO consensus definition. (C) 2003 Elsevier Inc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Edward Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO 63110 USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Div Radiat Oncol, Rochester, MN 55905 USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Thames, H (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Box 237,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 14 TC 144 Z9 149 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2003 VL 57 IS 4 BP 929 EP 943 DI 10.1016/S0360-3016(03)00631-X PG 15 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 738NB UT WOS:000186293800005 PM 14575823 ER PT J AU Randall, TC Armstrong, K AF Randall, TC Armstrong, K TI Differences in treatment and outcome between African-American and white women with endometrial cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RACIAL-DIFFERENCES; CARDIOVASCULAR PROCEDURES; ROGERS,WILL PHENOMENON; HOSPITAL VOLUME; SURVIVAL; CARCINOMA; SURGERY; IMPACT; STAGE; RACE AB Purpose: To investigate disparities in treatment and outcomes between African-American and white women with endometrial cancer. Patients and Methods: We analyzed 1992 to 1998 Surveillance, Epidemiology, and End Results data for 21,561 women with epithelial cancers of the endometrium. Sequential Cox proportional hazard models were used to determine the association between tumor characteristics (stage, grade, and histologic type), sociodemographic characteristics (age and marital status), and treatment (surgery and radiation therapy) and the racial difference in mortality. Results: The unadjusted hazard ratio (HR) for death from endometrial cancer for African-American women compared with white women was 2.57. However, African-American women were significantly more likely to present with advanced-stage disease and have poorly differentiated tumors or tumors with an unfavorable histologic type and were significantly less likely to undergo definitive surgery at all stages of disease. Adjusting for tumor and sociodemographic characteristics lowered the HR for African-American women to 1.80. Further adjustment for the use of surgery reduced the HR to 1.51. The association between surgery and survival was stronger among white women (HR, 0.26) than among African-American women (HR, 0.44). Conclusion: African-American women with endometrial cancer are significantly less likely to undergo primary surgery and have significantly shorter survival than white women with endometrial cancer. Racial differences in treatment are associated with racial differences in survival. The association between use of surgery and survival is weaker among African-American than white women, raising questions about potential racial differences in the effectiveness of surgery. (C) 2003 by American Society of Clinical Oncology. C1 Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1204 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 31 TC 60 Z9 60 U1 3 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 15 PY 2003 VL 21 IS 22 BP 4200 EP 4206 DI 10.1200/JCO.2003.01.218 PG 7 WC Oncology SC Oncology GA 745BW UT WOS:000186669300021 PM 14615448 ER PT J AU Re, F Strominger, JL AF Re, F Strominger, JL TI Separate functional domains of human MD-2 mediate toll-like receptor 4-binding and lipopolysaccharide responsiveness SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CUTTING EDGE; BACTERIAL LIPOPOLYSACCHARIDE; ENDOTHELIAL-CELLS; MOUSE MD-2; TLR4; LPS; CD14; PROTEIN; COMPLEX; MICE AB Cellular responses to LPS are mediated by a cell surface receptor complex consisting of Toll-like receptor 4 (TLR4), MD-2, and CD14. MD-2 is a secreted protein that interacts with the extracellular portion of TLR4. Site-directed mutagenesis was used to identify the regions of human MD-2 involved in its ability to bind TLR4 and confer LIPS responsiveness. A separate region of MD-2 was found to mediate each function. MD-2 binding to TLR4 was dependent on Cys(95) and Cys(105), which might form an intramolecular disulfide bond. Hydrophilic and charged residues surrounding this area, such as R90, K91, D100, and Y102, also contributed to the formation of the TLR4-MD-2 complex. A different region of MD-2 was found to be responsible for conferring LPS responsiveness. This region is not involved in TLR4 binding and is rich in basic and aromatic residues, several of which cooperate for LPS responsiveness and might represent a LIPS binding site. Disruption of the endogenous MD-2-TLR4 complex by expression of mutant MD-2 inhibited LIPS responses in primary human endothelial cells. Thus, our data indicate that MD-2 interaction with TLR4 is necessary but not sufficient for cellular response to LIPS. Either of the two functional domains of MD-2 can be disrupted to impair LPS responses and therefore represent attractive targets for therapeutic interventions. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Re, F (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,Dana 1414, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-4952402, AI-05466501] NR 26 TC 81 Z9 83 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2003 VL 171 IS 10 BP 5272 EP 5276 PG 5 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300042 PM 14607928 ER PT J AU Montalbano, A Ogwaro, KM Tang, A Matthews, AGW Larijani, M Oettinger, MA Feeney, AJ AF Montalbano, A Ogwaro, KM Tang, A Matthews, AGW Larijani, M Oettinger, MA Feeney, AJ TI V(D)J recombination frequencies can be profoundly affected by changes in the spacer sequence SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE SEGMENT USAGE; HEAVY-CHAIN GENES; TCR-BETA LOCUS; SIGNAL SEQUENCE; REARRANGEMENT FREQUENCY; STRUCTURE REQUIREMENTS; SOMATIC RECOMBINATION; NUCLEOTIDE-SEQUENCE; DNA-SEQUENCE; IN-VIVO AB Each V, D, and J gene segment is flanked by a recombination signal sequence (RSS), composed of a conserved heptamer and nonamer separated by a 12- or 23-bp spacer. Variations from consensus in the heptamer or nonamer at specific positions can dramatically affect recombination frequency, but until recently, it had been generally held that only the length of the spacer, but not its sequence, affects the efficacy of V(D)J recombination. In this study, we show several examples in which the spacer sequence can significantly affect recombination frequencies. We show that the difference in spacer sequence alone of two V(H)S107 genes affects recombination frequency in recombination substrates to a similar extent as the bias observed in vivo. We show that individual positions in the spacer can affect recombination frequency, and those positions can often be predicted by their frequency in a database of RSS. Importantly, we further show that a spacer sequence that has an infrequently observed nucleotide at each position is essentially unable to support recombination in an extrachromosmal substrate assay, despite being flanked by a consensus heptamer and nonamer. This infrequent spacer sequence RSS shows only a 2-fold reduction of binding of RAG proteins, but the in vitro cleavage of this RSS is similar to9-fold reduced compared with a good RSS. These data demonstrate that the spacer sequence should be considered to play an important role in the recombination efficacy of an RSS, and that the effect of the spacer occurs primarily subsequent to RAG binding. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Feeney, AJ (reprint author), Scripps Res Inst, Dept Immunol, IMM-22,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NCRR NIH HHS [M01 RR00833]; NIAID NIH HHS [R01 AI29672, AI37098]; NIGMS NIH HHS [R01 GM48026, T32 GM08303] NR 41 TC 24 Z9 24 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2003 VL 171 IS 10 BP 5296 EP 5304 PG 9 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300045 PM 14607931 ER PT J AU Verschoor, A Brockman, MA Gadjeva, M Knipe, DM Carroll, MC AF Verschoor, A Brockman, MA Gadjeva, M Knipe, DM Carroll, MC TI Myeloid C3 determines induction of humoral responses to peripheral herpes simplex virus infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLEMENT COMPONENT C3; FOLLICULAR DENDRITIC CELLS; IMMUNE-RESPONSE; T-CELLS; ACQUIRED-IMMUNITY; ANTIBODY-RESPONSE; COVALENT BINDING; LOCAL SYNTHESIS; LYMPHOCYTES-B; BONE-MARROW AB The complement system, in addition to its role in innate immunity, is an important regulator of the B cell response. Complement exists predominantly in the circulation and although the primary source is hepatic, multiple additional cellular sources have been described that can contribute substantially to the complement pool. To date, however, complement produced by these secondary sources has been deemed redundant to that secreted by the liver. In contrast, using a bone marrow chimeric model, we observed that C3 synthesis by myeloid cells, a relatively minor source of complement, provided a critical function during the induction of Immoral responses to peripheral HSV infection. Anti-viral Ab, as generated in an efficient Immoral response, has been associated with protection from severe consequences of HSV dissemination. This report offers insight into the generation of the adaptive immune response in the periphery and describes a unique role for a nonhepatic complement source. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. OI Brockman, Mark/0000-0001-6432-1426 FU NIAID NIH HHS [AI42257, P01AI42257, R01AI36389]; NINDS NIH HHS [P01NS35138] NR 63 TC 42 Z9 44 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 NOV 15 PY 2003 VL 171 IS 10 BP 5363 EP 5371 PG 9 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300053 PM 14607939 ER PT J AU Kawahara, T Ohdan, H Zhao, GL Yang, YG Sykes, M AF Kawahara, T Ohdan, H Zhao, GL Yang, YG Sykes, M TI Peritoneal cavity B cells are precursors of splenic IgM natural antibody-producing cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; MIXED CHIMERISM; B-1 CELLS; LYMPHOID FOLLICLES; CHEMOKINE RECEPTOR; IMMUNE-RESPONSES; EPITOPES; XENOTRANSPLANTATION; ACTIVATION AB Peritoneal cavity B-I cells are believed to produce IgM natural Abs. We have used alpha1,3-galactosyltransferase-deficient (GalT(-/-)) mice, which, like humans, produce IgM natural Abs against the carbohydrate epitope Galalpha1,3Gal (Gal), to demonstrate that peritoneal cavity B-1b cells with anti-Gal receptors produce anti-Gal IgM Abs only after LPS stimulation. Likewise, peritoneal cavity cells of GaIT-/- and wild-type mice do not produce IgM Abs of other specificities without LPS stimulation. Development of Ab-secreting capacity is associated with loss of CD11b/CD18 (Mac-1) expression. In contrast, there are large numbers of cells producing anti-Gal and other IgM Abs in fresh splenocyte preparations from GalT(-/-) and (for non-Gal specificities) wild-type mice. These cells are Mac-1(-) but otherwise B-1b-like in their phenotype. We therefore hypothesized a pathway wherein peritoneal cavity B cells migrate into the spleen after activation in vivo and lose Mac-1 expression to become IgM Ab-producing cells. Consistent with this possibility, splenectomy reduced anti-Gal Ab production after immunization of GaIT-/- mice with Gal-positive rabbit RBC. Furthermore, splenectomized B6 GalT(-/-), Ig mu-chain mutant (mu(-/-)) (both Gal- and B cell-deficient) mice produced less anti-Gal IgM than nonsplenectomized controls after adoptive transfer of peritoneal cavity cells from B6 GaIT-/- mice. When sorted GalT(-/-) Mac-1(+) peritoneal cavity B cells were adoptively transferred to B6 GaIT-/-, mu(-/-) mice, IgM Abs including anti-Gal appeared, and IgM-producing and Mac1(-) B cells were present in the spleen 5 wk after transfer. These findings demonstrate that peritoneal cavity Mac-1(+) B-I cells are precursors of Mac-1- splenic IgM Ab-secreting cells. C1 Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Sch Med, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [P01 HL18646] NR 48 TC 80 Z9 81 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2003 VL 171 IS 10 BP 5406 EP 5414 PG 9 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300058 PM 14607944 ER PT J AU Andrassy, J Kusaka, S Jankowska-Gan, E Torrealba, JR Haynes, LD Marthaler, BR Tam, RC Illigens, BMW Anosova, N Benichou, G Burlingham, WJ AF Andrassy, J Kusaka, S Jankowska-Gan, E Torrealba, JR Haynes, LD Marthaler, BR Tam, RC Illigens, BMW Anosova, N Benichou, G Burlingham, WJ TI Tolerance to noninherited maternal MHC antigens in mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; RENAL-TRANSPLANT RECIPIENT; DONOR-SPECIFIC TRANSFUSION; DOSE ORAL TOLERANCE; T-CELLS; ANTERIOR-CHAMBER; GRAFT-REJECTION; HLA ANTIGENS; ALLOANTIBODY PRODUCTION; ALLOGRAFT ACCEPTANCE AB The phenomenon of tolerance to noninherited maternal Ags (NIMA) is poorly understood. To analyze the NIMA effect C57BL/6 (H-2(b/b)) males were mated with B6D2F(1) (H-2(b/d)) females, whereby 50% of the offspring are H-2(b/b) mice that have been exposed to maternal H-2(d) alloantigens. Controls were H-2(b/b) offspring of C57BL/6 mothers, either inbred C57BL/6 mice or F, backcross mice from breedings with H-2(b/d) fathers. We found that 57% of the H-2(b/b) offspring of semiallogeneic (H-2b/d) mothers accepted fully allogeneic DBA/2 (H-2(d/d)) heart grafts for >180 days, while similar transplants were all rejected by day 11 in controls (p < 0.0004). Foster nursing studies showed that both oral and in utero exposure to NIMA are required for this tolerogenic effect. An effect of NIMA was also found to extend the survival of skin grafts from a semiallogeneic donor (p < 0.02). Pretransplant analysis of splenocytes showed a 40-90% reduction of IL-2-, IL-5-, and IFN-gamma-producing T cells responding to H-2(d)-expressing APC in NIMA(d)-exposed vs control mice. Injection of pregnant BALB/c-dm2 (H-2L(d)-negative) female mice i.v. with H-2L(61-80)(d) peptide profoundly suppressed the offspring's indirect pathway alloreactive CD4(+) T cell response to H-2L(d). These results suggest that the natural exposure of the fetus and newborn to maternal cells and/or soluble MHC Ags suppresses NIMA-allospecific T cells of the offspring, predisposing to organ transplant tolerance in adult mice. C1 Univ Wisconsin, Dept Surg, Madison, WI 53792 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53792 USA. Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol Surg Transplant & Surg Oncol, Okayama 7008530, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. ICN Pharmaceut, Costa Mesa, CA 92626 USA. RP Burlingham, WJ (reprint author), Univ Wisconsin, Dept Surg, Room G4-702 CSC, Madison, WI 53792 USA. FU NEI NIH HHS [R01EY13310]; NIAID NIH HHS [AI33704, K02AI01452, R01AI44077] NR 60 TC 56 Z9 61 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 NOV 15 PY 2003 VL 171 IS 10 BP 5554 EP 5561 PG 8 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300077 PM 14607963 ER PT J AU Fishman, JA AF Fishman, JA TI Transplantation for patients infected with human immunodeficiency virus: No longer experimental but not yet routine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID HEPATITIS-C VIRUS; SOLID-ORGAN TRANSPLANTATION; ACTIVE ANTIRETROVIRAL THERAPY; HIV-ASSOCIATED NEPHROPATHY; INJECTION-DRUG USERS; SOCIETY-USA PANEL; LIVER-TRANSPLANTATION; RENAL-DISEASES; CLINICAL-COURSE; AIDS C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 74 TC 16 Z9 17 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 NOV 15 PY 2003 VL 188 IS 10 BP 1405 EP 1411 DI 10.1086/379256 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 745GW UT WOS:000186681800001 PM 14624364 ER PT J AU Oberdoerffer, P Otipoby, KL Maruyama, M Rajewsky, K AF Oberdoerffer, P Otipoby, KL Maruyama, M Rajewsky, K TI Unidirectional Cre-mediated genetic inversion in mice using the mutant loxP pair lox66/lox71 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SITE-SPECIFIC RECOMBINATION; PROTEIN TRANSDUCTION; CELL-DEVELOPMENT; MOUSE; IMMUNOGLOBULIN; DNA; INTEGRATION; DELIVERY; RECEPTOR; REGION AB The Cre/loxP recombination system is a commonly used tool to alter the mouse genome in a conditional manner by deletion or inversion of loxP-flanked DNA segments. While Cre-mediated deletion is essentially unidirectional, inversion is reversible and therefore does not allow the stable alteration of gene function in cells that constitutively express Cre. Site-directed mutagenesis yielded a pair of asymmetric loxP sites (lox66 and lox71) that display a favorable forward reaction equilibrium. Here, we demonstrate that lox66/lox71 mediates efficient and predominantly unidirectional inversion of a switch substrate targeted to the mouse genome in combination with either inducible or cell type-specific cre-transgenes in vivo. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Cologne, Inst Genet, D-50932 Cologne, Germany. Natl Inst Longev Sci, Pathol Lab, Dept Basic Gerontol, Obu, Aichi 4748522, Japan. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA92625-0, P01 CA092625]; NIAID NIH HHS [R37 AI054636] NR 28 TC 34 Z9 36 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 2003 VL 31 IS 22 AR e140 DI 10.1093/nar/gng140 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743TX UT WOS:000186590600039 PM 14602933 ER PT J AU Zelen, M AF Zelen, M TI The training of biostatistical scientists SO STATISTICS IN MEDICINE LA English DT Article C1 Harvard Univ, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zelen, M (reprint author), Harvard Univ, Boston, MA 02115 USA. NR 2 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 2003 VL 22 IS 21 BP 3427 EP 3430 DI 10.1002/sim.1642 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 737RK UT WOS:000186245400018 PM 14566925 ER PT J AU Zhong, WM Reche, PA Lai, CC Reinhold, B Reinherz, EL AF Zhong, WM Reche, PA Lai, CC Reinhold, B Reinherz, EL TI Genome-wide characterization of a viral cytotoxic T lymphocyte epitope repertoire SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLASS-I MOLECULES; SENDAI-VIRUS-INFECTION; CELL RESPONSE; CTL RESPONSES; MHC MOLECULES; PEPTIDES; ANTIGEN; IMMUNODOMINANCE; MOTIFS; VIVO AB A genome-wide search using major histocompatibility complex (MHC) class I binding and proteosome cleavage site algorithms identified 101 influenza A PR8 virus-derived peptides as potential epitopes for CD8(+) T cell recognition in the H-2(b) mouse. Cytokine-based flow cytometry, ELISPOT, and cytotoxic T lymphocyte assays reveal that 16 are recognized by CD8(+) T cells recovered directly ex vivo from infected animals, accounting for greater than 70% of CD8(+) T cells recruited to lung after primary infection. Only six of the 22 highest affinity MHC class I binding peptides comprise cytotoxic T lymphocyte epitopes. The remaining non-immunogenic peptides have equivalent MHC affinity and MHC-peptide complex half-lives, eliciting T cell responses when given in adjuvant and with T cell receptor-ligand avidity comparable with their immunogenic counterparts. As revealed by a novel high sensitivity nanospray tandem mass spectrometry methodology, failure to process those predicted epitopes may contribute significantly to the absent response. These results have important implications for rationale design of CD8(+) T cell vaccines. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 FU NIAID NIH HHS [AI50900] NR 44 TC 59 Z9 61 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 2003 VL 278 IS 46 BP 45135 EP 45144 DI 10.1074/jbc.M307417200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300013 PM 12960169 ER PT J AU Huber, WE Price, ER Widlund, HR Du, JY Davis, IJ Wegner, M Fisher, DE AF Huber, WE Price, ER Widlund, HR Du, JY Davis, IJ Wegner, M Fisher, DE TI A tissue-restricted cAMP transcriptional response - SOX10 modulates alpha-melanocyte-stimulating hormone-triggered expression of microphthalmia-associated transcription factor in melanocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WAARDENBURG-SYNDROME; FACTOR GENE; MOUSE MODEL; PROMOTER; MITF; ACTIVATION; PAX3; MUTATION; DEAFNESS; PATHWAY AB alpha-Melanocyte-stimulating hormone (MSH) utilizes cAMP to trigger pigmentation of melanocytes via activation of melanocyte-restricted microphthalmia-associated transcription factor (M-MITF) expression. M-MITF is a melanocyte-restricted helix-loop-helix transcription factor capable of transactivating promoters for multiple genes whose products modulate pigmentation. Although M-MITF promoter activation by MSH is known to occur through a conserved cAMP-response element (CRE), it remains unclear how this CRE exhibits such exquisitely tissue-restricted responsiveness. Here we show that cAMP-mediated CRE-binding protein activation of the M-MITF promoter requires a second DNA element located similar to100 bp upstream, a site that is bound and activated by SOX10. Mutations in the SOX10 transcription factor, like MITF, results in a disorder known as Waardenburg Syndrome. The cAMP response of the M-MITF promoter was analyzed in melanoma and neuroblastoma cells (which are neural crest-derived but lack both M-MITF and SOX10 expression). M-MITF promoter responsiveness to cAMP was found to depend upon SOX10, and reciprocally, SOX10 transactivation was dependent upon the CRE. Ectopic SOX10 expression, in cooperation with cAMP signaling, activated the M-MITF promoter function and the expression of measurable endogenous M-MITF transcripts in neuroblastoma cells. SOX10(dom), a mutant allele, failed to cooperate with cAMP in neuroblastoma cells and attenuated the cAMP responsiveness of the M-MITF promoter in melanoma cells. These observations demonstrate a means whereby the ubiquitous cAMP signaling machinery is harnessed to produce a highly tissue-restricted transcriptional response by cooperating with architectural factors, in this case SOX10. C1 Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Univ Erlangen Nurnberg, Inst Biochem, D-91054 Erlangen, Germany. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Div Pediat Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. OI Wegner, Michael/0000-0002-4586-3294 FU NIAMS NIH HHS [AR43369] NR 27 TC 53 Z9 55 U1 1 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 NOV 14 PY 2003 VL 278 IS 46 BP 45224 EP 45230 DI 10.1074/jbc.M309036200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300023 PM 12944398 ER PT J AU Tesco, G Koh, YH Tanzi, RE AF Tesco, G Koh, YH Tanzi, RE TI Caspase activation increases beta-amyloid generation independently of caspase cleavage of the beta-amyloid precursor protein (APP) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-SECRETASE ACTIVITIES; ALZHEIMERS-DISEASE; CEREBRAL-ISCHEMIA; APOPTOSIS; PEPTIDES; INVOLVEMENT; PRESENILIN; PROTEASES; A-BETA-42; PATHWAY AB The amyloid precursor protein (APP) undergoes "alternative" proteolysis mediated by caspases. Three major caspase recognition sites have been identified in the APP, i.e. one at the C terminus (Asp(720)) and two at the N terminus (Asp(197) and Asp(219)). Caspase cleavage at Asp(720) has been suggested as leading to increased production of Abeta. Thus, we set out to determine which putative caspase sites in APP, if any, are cleaved in Chinese hamster ovary cell lines concurrently with the increased Abeta production that occurs during apoptosis. We found that cleavage at Asp(720) occurred concurrently with caspase 3 activation and the increased production of total secreted Abeta and Abeta(1-42) in association with staurosporine- and etoposide-induced apoptosis. To investigate the contribution of caspase cleavage of APP to Abeta generation, we expressed an APP mutant truncated at Asp(720) that mimics APP caspase cleavage at the C-terminal site. This did not increase Abeta generation but, in contrast, dramatically decreased Abeta production in Chinese hamster ovary cells. Furthermore, the ablation of caspase-dependent cleavage at Asp(720), Asp(197), and Asp(219) (by site-directed mutagenesis) did not prevent enhanced Abeta production following etoposide-induced apoptosis. These findings indicate that the enhanced Abeta generation associated with apoptosis does not require cleavage of APP at its C-terminal (Asp(720)) and/or N-terminal caspase sites. C1 Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Genet & Aging Res Unit, Bldg 114,16th St C3009, Charlestown, MA 02129 USA. FU NIA NIH HHS [5P01 AG15379] NR 28 TC 36 Z9 36 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 NOV 14 PY 2003 VL 278 IS 46 BP 46074 EP 46080 DI 10.1074/jbc.M307809200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300124 PM 12960154 ER PT J AU Lingohr, MK Dickson, LM Wrede, CE Briaud, I McCuaig, JF Myers, MG Rhodes, CJ AF Lingohr, MK Dickson, LM Wrede, CE Briaud, I McCuaig, JF Myers, MG Rhodes, CJ TI Decreasing IRS-2 expression in pancreatic beta-cells (INS-1) promotes apoptosis, which can be compensated for by introduction of IRS-4 expression SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE insulin receptor substrate-2 (IRS-2); pancreatic beta-cell; apoptosis; signal transduction; free fatty acid ID RECEPTOR SUBSTRATE 2; INDUCED INSULIN-RESISTANCE; PROTEIN-KINASE-B; FREE FATTY-ACIDS; PROINSULIN BIOSYNTHESIS; DIFFERENTIAL ACTIVATION; SIGNAL-TRANSDUCTION; GLUCOSE-HOMEOSTASIS; ISLET CELLS; GROWTH AB IRS-2 plays a pivotal role in the control of pancreatic P-cell growth. Here, the effect of altering IRS-2 expression levels in the pancreatic p-cell line, INS-1, was examined. Adenoviral-mediated increased in IRS-2 protein levels protected against fatty acid (FFA)-induced apoptosis, associated with increased activation of PKB and decreased levels of activated caspase-9. Conversely, decreasing endogenous IRS-2 in INS-1 cells, using adenoviral-mediated expression of IRS-2 antisense, caused a three-fold increase in baseline apoptosis that was further enhanced in the presence of FFA. This was associated with decreased activation of PKB and increased caspase-9 activation. Although IRS-4 is not normally expressed in p-cells, it was found that adenoviral-mediated introduction of IRS-4 into INS-1 cells enhanced glucose/IGF-1 induced mitogenesis, and protected against FFA-induced apoptosis, similarly to IRS-2. Moreover, expression of IRS-4 in INS-1 cells depleted of IRS-2 levels by IRS-2 antisense, was able to compensate for the lack of IRS-2 and reduce apoptosis in these cells back to normal. Thus, in P-cells IRS-4 and -2 have similar biological functions. Also, this study further emphasizes the importance of IRS-2 signaling in control of p-cell survival. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Pacific NW Res Inst, Seattle, WA 98122 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98122 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Rhodes, CJ (reprint author), Pacific NW Res Inst, 720 Broadway, Seattle, WA 98122 USA. FU NIDDK NIH HHS [DK 55269, DK60266] NR 47 TC 50 Z9 54 U1 0 U2 1 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 NOV 14 PY 2003 VL 209 IS 1-2 BP 17 EP 31 DI 10.1016/j.mce.2003.08.003 PG 15 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 745CD UT WOS:000186670000003 PM 14604813 ER PT J AU Kodama, S Kuhtreiber, W Fujimura, S Dale, EA Faustman, DL AF Kodama, S Kuhtreiber, W Fujimura, S Dale, EA Faustman, DL TI Islet regeneration during the reversal of autoimmune diabetes in NOD mice SO SCIENCE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW CELLS; IN-VIVO; ADULT MICE; DIFFERENTIATE; FUSION; HEPATOCYTES; BRAIN; PROGENITORS; EXPRESSION AB Nonobese diabetic (NOD) mice are a model for type 1 diabetes in humans. Treatment of NOD mice with end-stage disease by injection of donor splenocytes and complete Freund's adjuvant eliminates autoimmunity and permanently restores normoglycemia. The return of endogenous insulin secretion is accompanied by the reappearance of pancreatic beta cells. We now show that live donor male or labeled splenocytes administered to diabetic NOD females contain cells that rapidly differentiate into islet and ductal epithelial cells within the pancreas. Treatment with irradiated splenocytes is also followed by islet regeneration, but at a slower rate. The islets generated in both instances are persistent, functional, and apparent in all NOD hosts with permanent disease reversal. C1 Massachusetts Gen Hosp, Immunobiol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Lab, Bldg 149,13th St,Room 3602, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [P30 DK57521-02] NR 36 TC 232 Z9 256 U1 2 U2 4 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 NOV 14 PY 2003 VL 302 IS 5648 BP 1223 EP 1227 DI 10.1126/science.1088949 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 742XW UT WOS:000186544300058 PM 14615542 ER PT J AU Ballantyne, JC Mao, JR AF Ballantyne, JC Mao, JR TI Opioid therapy for chronic pain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CHRONIC NONMALIGNANT PAIN; PLACEBO-CONTROLLED-TRIAL; CONTROLLED-RELEASE OXYCODONE; CHRONIC NEUROPATHIC PAIN; LONG-TERM USE; MORPHINE-TOLERANCE; DOUBLE-BLIND; POSTHERPETIC NEURALGIA; NONCANCER PAIN; OSTEOARTHRITIS PAIN C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Pain Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Pain Ctr, 15 Parkman St,WACC 333, Boston, MA 02114 USA. FU NIDA NIH HHS [R01DA08835] NR 102 TC 469 Z9 479 U1 2 U2 28 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 NOV 13 PY 2003 VL 349 IS 20 BP 1943 EP 1953 DI 10.1056/NEJMra025411 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 742EA UT WOS:000186502400011 PM 14614170 ER PT J AU Overdeck, DL Brugge, WR Pitman, MB Lewandrowski, KB Harris, NL Warshaw, AL AF Overdeck, DL Brugge, WR Pitman, MB Lewandrowski, KB Harris, NL Warshaw, AL TI Case 35-2003: A 75-year-old man with a cystic lesion of the pancreas - Intraductal papillary mucinous carcinoma of the pancreas, arising in an intraductal papillary mucinous neoplasm and involving both the main pancreatic duct and a side branch SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DIFFERENTIAL-DIAGNOSIS; FLUID ANALYSIS; TUMOR C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Overdeck, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 13 TC 6 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 13 PY 2003 VL 349 IS 20 BP 1954 EP 1961 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 742EA UT WOS:000186502400012 ER PT J AU Martemyanov, KA Lishko, PV Calero, N Keresztes, G Sokolov, M Strissel, KJ Leskov, IB Hopp, JA Kolesnikov, AV Chen, CK Lem, J Heller, S Burns, ME Arshavsky, VY AF Martemyanov, KA Lishko, PV Calero, N Keresztes, G Sokolov, M Strissel, KJ Leskov, IB Hopp, JA Kolesnikov, AV Chen, CK Lem, J Heller, S Burns, ME Arshavsky, VY TI The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo SO JOURNAL OF NEUROSCIENCE LA English DT Article DE DEP domains; RGS proteins; SNARE proteins; protein targeting; photoreceptors; retina ID MEDIATED MEMBRANE-FUSION; ACCELERATING PROTEIN; PHOTORECEPTOR-MEMBRANES; ROD PHOTORESPONSE; OUTER SEGMENT; TRANSDUCIN; COMPLEX; RHODOPSIN; REGULATOR; ANCHOR AB DEP (for Disheveled, EGL-10, Pleckstrin) homology domains are present in numerous signaling proteins, including many in the nervous system, but their function remains mostly elusive. We report that the DEP domain of a photoreceptor-specific signaling protein, RGS9 (for regulator of G-protein signaling 9), plays an essential role in RGS9 delivery to the intracellular compartment of its functioning, the rod outer segment. We generated a transgenic mouse in which RGS9 was replaced by its mutant lacking the DEP domain. We then used a combination of the quantitative technique of serial tangential sectioning-Western blotting with electrophysiological recordings to demonstrate that mutant RGS9 is expressed in rods in the normal amount but is completely excluded from the outer segments. The delivery of RGS9 to rod outer segments is likely to be mediated by the DEP domain interaction with a transmembrane protein, R9AP (for RGS9 anchoring protein), known to anchor RGS9 on the surface of photoreceptor membranes and to potentiate RGS9 catalytic activity. We show that both of these functions are also abolished as the result of the DEP domain deletion. These findings indicate that a novel function of the DEP domain is to target a signaling protein to a specific compartment of a highly polarized neuron. Interestingly, sequence analysis of R9AP reveals the presence of a conserved R-SNARE (for soluble N-ethylmaleimide-sensitive factor attachment protein receptor) motif and a predicted overall structural homology with SNARE proteins involved in vesicular trafficking and fusion. This presents the possibility that DEP domains might serve to target various DEP-containing proteins to the sites of their intracellular action via interactions with the members of extended SNARE protein family. C1 Harvard Univ, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. Univ Calif Davis, Dept Psychiat, Davis, CA 95616 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Univ Utah, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84112 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, Sch Med, Genet Program, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 12859, EY12008, EY14147, R01 EY014047, R01 EY014047-03]; NHLBI NIH HHS [P50HL63494]; NIDCD NIH HHS [DC04563] NR 41 TC 73 Z9 78 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 12 PY 2003 VL 23 IS 32 BP 10175 EP 10181 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 742UH UT WOS:000186536100001 PM 14614075 ER PT J AU Revzin, A Tompkins, RG Toner, M AF Revzin, A Tompkins, RG Toner, M TI Surface engineering with poly(ethylene glycol) photolithography to create high-density cell arrays on glass SO LANGMUIR LA English DT Article ID PROTEIN ADSORPTION; SANDWICH CONFIGURATION; FORCE MICROSCOPY; MAMMALIAN-CELL; ADHESION; FILMS; MICROFABRICATION; HEPATOCYTES; MONOLAYERS; COCULTURES AB This manuscript presents a microfabrication-derived approach for controlling mammalian cell-surface interactions. Poly(ethylene glycol)-diacrylate (PEG-DA) was patterned, in a process analogous to photolithography, to manufacture high-density arrays of micrometer-scale PEG hydrogel wells on glass. Individual wells consisted of PEG walls and glass attachment pads; thus, as a result of the biological inertness of PEG, microwell patterning created a highly ordered biointerface with modulating-cell or protein-repellent properties. Fabricated hydrogel microstrucures proved very effective in guiding and confining adhesion of transformed 3T3 fibroblasts and primary rat hepatocytes to defined regions on the glass substrate. PEG-patterned glass surfaces were selectively modified with collagen (type I) to induce hepatocyte attachment. Localization of the fluorescein-conjugated collagen within the glass attachment pads of PEG hydrogel microwells was visualized by fluorescence microscopy. Further surface analysis was performed by tapping mode atomic force microscopy conducted within individual PEG wells. Protein-modified regions inside the wells had a root-mean-square roughness of 1.13 +/- 0.03 nm compared to 0.7 +/- 0.04 nm for alkylsilane-treated regions lacking protein. The cell occupancy of 96.7 +/- 1.9% within the arrays of 30 x 30 mum individual wells was demonstrated for 3T3 fibroblasts. At the same time, cells remained effectively isolated in the individual PEG microwells. Primary hepatocytes attached and became fully confluent within the collagen-coated PEG after 24 h of incubation. Each 30 x 30 mum well contained one to three hepatocytes. Cells patterned on the surface remained viable after 24 h of incubation. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Toner, M (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. RI Yu, weiting/I-7417-2013 NR 48 TC 187 Z9 189 U1 4 U2 63 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD NOV 11 PY 2003 VL 19 IS 23 BP 9855 EP 9862 DI 10.1021/la035129b PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 741XC UT WOS:000186484800047 ER PT J AU Cestari, DM Rizzo, JF AF Cestari, DM Rizzo, JF TI Intracranial hypertension following epidural blood patch SO NEUROLOGY LA English DT Editorial Material ID AUTOLOGOUS BLOOD; INJECTION; PUNCTURE C1 Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Rizzo, JF (reprint author), Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 8 Z9 8 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 NOV 11 PY 2003 VL 61 IS 9 BP 1303 EP 1303 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 741UT UT WOS:000186479300036 PM 14610148 ER PT J AU Chong, PST Vucic, S Cros, DP AF Chong, PST Vucic, S Cros, DP TI Multiple sclerosis presenting as lower motor neuron wasting and weakness of the distal upper extremity SO NEUROLOGY LA English DT Editorial Material ID NEUROPATHY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vucic, S (reprint author), 55 Fruit St, Boston, MA 02114 USA. NR 7 TC 4 Z9 4 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 NOV 11 PY 2003 VL 61 IS 9 BP 1303 EP 1304 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 741UT UT WOS:000186479300037 ER PT J AU Nogueira, RG Seeley, WW AF Nogueira, RG Seeley, WW TI Ramsay Hunt syndrome associated with spinal trigeminal nucleus and tract involvement on MRI SO NEUROLOGY LA English DT Editorial Material ID HERPES-ZOSTER; ENCEPHALITIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Blake 12 Room 1291,55 Fruit St, Boston, MA 02114 USA. NR 7 TC 9 Z9 10 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 NOV 11 PY 2003 VL 61 IS 9 BP 1306 EP 1307 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 741UT UT WOS:000186479300040 PM 14610151 ER PT J AU Li, HW Roblin, G Liu, H Heller, S AF Li, HW Roblin, G Liu, H Heller, S TI Generation of hair cells by stepwise differentiation of embryonic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOUSE INNER-EAR; GROWTH-FACTOR-I; EXPRESSION; PROLIFERATION; INDUCTION; NEURONS; MATH1; GENE; STEREOCILIA; FIBROBLAST AB The increase in life expectancy is accompanied by the growing burden of chronic diseases. Hearing loss is perhaps the most prevalent of all chronic diseases. In addition to age-related hearing loss, a substantial number of cases of audiological impairment are either congenital in nature or acquired during childhood. The permanence of hearing loss is mainly due to the inability of the cochlear sensory epithelium to replace lost mechanoreceptor cells, or hair cells. Generation of hair cells from a renewable source of progenitors that can be transplanted into damaged inner ears is a principal requirement for potential cell replacement therapy in this organ. Here, we present an experimental protocol that enables us to routinely create inner ear progenitors from murine embryonic stem cells in vitro. These progenitors express a comprehensive set of marker genes that define the developing inner ear, in particular the organ's developing sensory patches. We further demonstrate that cells that express markers characteristic of hair cells differentiate from embryonic stem cell-derived progenitors. Finally, we show that these progenitors integrate into the developing inner ear at sites of epithelial injury and that integrated cells start expressing hair cell markers and display hair bundles when situated in cochlear or vestibular sensory epithelia in vivo. C1 Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Heller, S (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC006167, DC006167] NR 38 TC 148 Z9 175 U1 1 U2 25 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 NOV 11 PY 2003 VL 100 IS 23 BP 13495 EP 13500 DI 10.1073/pnas.2334503100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743LR UT WOS:000186573700069 PM 14593207 ER PT J AU Rubin, JB Kung, AL Klein, RS Chan, JA Sun, YP Schmidt, K Kieran, MW Luster, AD Segal, RA AF Rubin, JB Kung, AL Klein, RS Chan, JA Sun, YP Schmidt, K Kieran, MW Luster, AD Segal, RA TI A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; SIGNAL-REGULATED KINASES-1/2; CELL-DERIVED FACTOR-1; HUMAN GLIOBLASTOMA; EXPRESSION; CANCER; PROLIFERATION; METASTASIS; ASTROCYTES; MIGRATION AB The vast majority of brain tumors in adults exhibit glial characteristics. Brain tumors in children are diverse: Many have neuronal characteristics, whereas others have glial features. Here we show that activation of the G(i) protein-coupled receptor CXCR4 is critical for the growth of both malignant neuronal and glial tumors. Systemic administration of CXCR4 antagonist AMD 3100 inhibits growth of intracranial glioblastoma and medulloblastoma xenografts by increasing apoptosis and decreasing the proliferation of tumor cells. This reflects the ability of AMD 3100 to reduce the activation of extracellular signal-regulated kinases 1 and 2 and Akt, all of which are pathways downstream of CXCR4 that promote survival, proliferation, and migration. These studies (i) demonstrate that CXCR4 is critical to the progression of diverse brain malignances and (ii) provide a scientific rationale for clinical evaluation of AMD 3100 in treating both adults and children with malignant brain tumors. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. OI Kieran, Mark/0000-0003-2184-7692; Kung, Andrew/0000-0002-9091-488X NR 45 TC 453 Z9 473 U1 2 U2 13 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 NOV 11 PY 2003 VL 100 IS 23 BP 13513 EP 13518 DI 10.1073/pnas.2235846100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743LR UT WOS:000186573700072 PM 14595012 ER PT J AU Kleine-Lowinski, K Rheinwald, JG Fichorova, RN Anderson, DJ Basile, J Munger, K Daly, CM Rosl, F Rollins, BJ AF Kleine-Lowinski, K Rheinwald, JG Fichorova, RN Anderson, DJ Basile, J Munger, K Daly, CM Rosl, F Rollins, BJ TI Selective suppression of monocyte chemoattractant protein-1 expression by human papillomavirus E6 and E7 oncoproteins in human cervical epithelial and epidermal cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cervical cancer; human papillomavirus; E6; E7; chemokine; monocyte chemoattractant protein-I ID HUMAN KERATINOCYTES; IFN-GAMMA; INTRAEPITHELIAL NEOPLASIA; ANTIGEN PRESENTATION; MCP-1 GENE; T-CELLS; TYPE-16; DIFFERENTIATION; P53; TRANSCRIPTION AB Infection of cervical keratinocytes by high-risk HPV is involved in the etiology of cervical carcinoma. Since viral products are immunogenic, development of cancer may require suppression of immune responses directed against infected epithelial cells. Many markers of host immune effector responses decrease as cervical intraepithelial neoplasia progresses. Among these is epithelial cell expression of the chemokine MCP-I, though the mechanism for its suppression is unclear. Here, we show that the E6 and E7 viral oncogenes from high-risk HPV, individually and together, suppress MCP-I expression in primary epithelial cells derived from the female genital tract. This is not a consequence of global suppression of chemokine expression since other chemokines, including IP-10, IL-8 and RANTES, were less affected. Furthermore, 4 of 6 HPV-positive cervical carcinoma cell lines did not express MCP-I. Our data indicate that suppression of MCP-I expression is part of the program of high-risk HPV E6/E7-induced transformation of primary epithelial cells. These observations are consistent with a model in which MCP-I expression by infected keratinocytes, which would stimulate an immune attack on HPV-transformed cells, is suppressed for invasive cervical cancer to appear. (C) 2003 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Fichorova, Raina/G-9969-2014; OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [CA53091]; NIAMS NIH HHS [P30 AR042689]; NIDCR NIH HHS [R01 DE013178] NR 32 TC 41 Z9 46 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 10 PY 2003 VL 107 IS 3 BP 407 EP 415 DI 10.1002/ijc.11411 PG 9 WC Oncology SC Oncology GA 733DK UT WOS:000185984500012 PM 14506741 ER PT J AU Brau, N AF Brau, N TI Update on chronic hepatitis C in HIV/HCV-coinfected patients: viral interactions and therapy SO AIDS LA English DT Review DE HIV; hepatitis C virus; coinfection; HAART; ribavirin; interferon; combination therapy; liver disease ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; ACTIVE ANTIRETROVIRAL THERAPY; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; SUSTAINED VIROLOGICAL RESPONSE; HEPATOCELLULAR-CARCINOMA; COMBINATION THERAPY; DRUG-USERS; INITIAL TREATMENT; RANDOMIZED-TRIAL AB With highly active antiretroviral therapy (HAART), HIV-infected patients can now live longer and healthier lives, and other comorbid diseases, such as chronic hepatitis C, have emerged as a significant health concern. Coinfection with the hepatitis C virus (HCV) may limit life expectancy because it can lead to serious liver disease including decompensated liver cirrhosis and hepatocellular carcinoma. HCV-induced fibrosis progresses faster in HIV/HCV-coinfected persons, although HAART may be able to decrease this disease acceleration. Combination therapy for HCV with interferon and ribavirin can achieve a sustained viral response, although at a lower rate than in HCV-monoinfected patients. Combination treatment with pegylated interferon and ribavirin will probably emerge as the next HCV therapy of choice for HIV/HCV-coinfected patients. HCV combination therapy is generally safe, but serious adverse reactions, like lactic acidosis, may occur. Cytopenia may present a problem leading to dose reductions, but the role of growth factors is under study. All HIV/HCV-coinfected patients should be evaluated for therapy against the hepatitis C virus. A sustained viral load will probably lead to regression of liver disease, and even interferon-based treatment without viral clearance may slow down progression of liver disease. HIV/HCV-coinfected patients who have progressed to end-stage liver disease have few therapeutic options other than palliative care, since liver transplants are generally unavailable. The mortality post-transplant may be higher than in HCV-monoinfected patients. We are entering an era where safe and effective HCV therapy is being defined for HIV/HCV-coinfected patients, and all eligible patients should be offered treatment. C1 Bronx Vet Affairs Med Ctr, Infect Dis Sect 111F, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY USA. RP Brau, N (reprint author), Bronx Vet Affairs Med Ctr, Infect Dis Sect 111F, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 101 TC 35 Z9 40 U1 1 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 NOV 7 PY 2003 VL 17 IS 16 BP 2279 EP 2290 DI 10.1097/01.aids.0000088176.01779.19 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 809YO UT WOS:000220672200002 PM 14571179 ER PT J AU Hinoi, T Loda, M Fearon, ER AF Hinoi, T Loda, M Fearon, ER TI Silencing of CDX2 expression in colon cancer via a dominant repression pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID E-CADHERIN EXPRESSION; HOMEOBOX GENE CDX2; COLORECTAL-CANCER; PROTEIN EXPRESSION; BREAST-CANCER; MUTANT MICE; CARCINOMAS; EPITHELIUM; DROSOPHILA; CELLS AB CDX2 is a caudal-related homeobox transcription factor whose expression in the adult is normally restricted to intestinal epithelium. Mice heterozygous for germ line Cdx2 inactivation develop intestinal polyps, and the lesions lack Cdx2 expression. Prior studies indicate some human colon carcinomas also lack CDX2 expression. To address the role of CDX2 defects in colon cancer development, we analyzed CDX2 expression in 45 primary colorectal carcinomas. Four carcinomas lacked CDX2 expression, and three others showed aberrant cytoplasmic localization of CDX2, although no significant CDX2 gene defects were seen in the seven tumors. Marked reductions in CDX2 transcript and protein levels were seen in five of 13 colorectal cell lines, and nuclear run-off data indicated reduced transcription was a major factor in CDX2 silencing. Treatment with the DNA demethylating agent 5-aza- 2'-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A did not restore CDX2 expression in CDX2-negative lines. However, consistent with a role for dominant repression mechanisms in CDX2 silencing, all somatic cell hybrids resulting from pairwise fusions between colon cancer lines with intact CDX2 expression and lines lacking CDX2 had reduced CDX2 transcripts and protein. A roughly 9.5-kb 5'-flanking region from the human CDX2 gene contained key cis elements for regulating transcription in colon cancer cells. Restoration of CDX2 expression suppressed proliferation and soft agar growth in the CDX2-negative HT-29 colon cancer cell line. Our findings suggest CDX2 inactivation in colon cancer results from defects in trans-acting pathways regulating CDX2 transcription, and CDX2 silencing contributes to the altered phenotype of some colorectal cancers. C1 Univ Michigan, Med Ctr, Div Mol Med & Genet, Dept Internal Med,Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Ctr Canc, Ann Arbor, MI 48109 USA. Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Adult Oncol, Boston, MA 02115 USA. RP Fearon, ER (reprint author), Univ Michigan, Med Ctr, Div Mol Med & Genet, Dept Internal Med,Sch Med, 1150 W Med Ctr Dr,4301 MSRB 3, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [CA82223] NR 37 TC 74 Z9 76 U1 2 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 NOV 7 PY 2003 VL 278 IS 45 BP 44608 EP 44616 DI 10.1074/jbc.M307435200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700091 PM 12947088 ER PT J AU Gunaratnam, L Morley, M Franovic, A de Paulsen, N Mekhail, K Parolin, DAE Nakamura, E Lorimer, IAJ Lee, S AF Gunaratnam, L Morley, M Franovic, A de Paulsen, N Mekhail, K Parolin, DAE Nakamura, E Lorimer, IAJ Lee, S TI Hypoxia inducible factor activates the transforming growth factor-alpha/epidermal growth factor receptor growth stimulatory pathway in VHL-/- renal cell carcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LINDAU TUMOR-SUPPRESSOR; UBIQUITIN LIGASE COMPLEX; FACTOR-ALPHA; FAMILIAL PHEOCHROMOCYTOMA; PROLYL HYDROXYLATION/; GERMLINE MUTATIONS; TYROSINE KINASE; GENE-EXPRESSION; CANCER-CELLS; REGULATE HIF AB Bi-allelic-inactivating mutations of the VHL tumor suppressor gene are found in the majority of clear cell renal cell carcinomas (VHL-/- RCC). VHL-/- RCC cells overproduce hypoxia-inducible genes as a consequence of constitutive, oxygen-independent activation of hypoxia inducible factor (HIF). While HIF activation explains the highly vascularized nature of VHL loss lesions, the relative role of HIF in oncogenesis and loss of growth control remains unknown. Here, we report that HIF plays a central role in promoting unregulated growth of VHL-/- RCC cells by activating the transforming growth factor-alpha (TGF-alpha)/epidermal growth factor receptor (EGF-R) pathway. Dominant-negative HIF and enzymatic inhibition of EGF-R were equally efficient at abolishing EGF-R activation and serum-independent growth of VHL-/- RCC cells. TGF-alpha is the only known EGF-R ligand that has a VHL-dependent expression profile and its overexpression by VHL-/- RCC cells is a direct consequence of HIF activation. In contrast to TGF-alpha, other HIF targets, including vascular endothelial growth factor ( VEGF), were unable to stimulate serum-independent growth of VHL-/- RCC cells. VHL-/- RCC cells expressing reintroduced type 2C mutants of VHL, and which retain the ability to degrade HIF, fail to overproduce TGF-alpha and proliferate in serum-free media. These data link HIF with the overproduction of a bona fide renal cell mitogen leading to activation of a pathway involved in growth of renal cancer cells. Moreover, our results suggest that HIF might be involved in oncogenesis to a much higher extent than previously appreciated. C1 Univ Ottawa, Fac Med, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada. Univ Ottawa, Fac Med, Kidney Res Ctr, Ottawa, ON K1H 8M5, Canada. Univ Ottawa, Fac Med, Dept Internal Med, Ottawa, ON K1H 8M5, Canada. Univ Ottawa, Fac Med, Ottawa Reg Canc Ctr, Ottawa, ON K1H 8M5, Canada. Univ Ottawa, Fac Med, Dept Biochem & Immunol, Ottawa, ON K1H 8M5, Canada. Harvard Univ, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Lee, S (reprint author), Univ Ottawa, Fac Med, Dept Cellular & Mol Med, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. NR 80 TC 129 Z9 141 U1 0 U2 5 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 NOV 7 PY 2003 VL 278 IS 45 BP 44966 EP 44974 DI 10.1074/jbc.M305502200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700133 PM 12944410 ER PT J AU Cross, AS Opal, SM Palardy, JE Drabick, JJ Warren, HS Huber, C Cook, P Bhattacharjee, AK AF Cross, AS Opal, SM Palardy, JE Drabick, JJ Warren, HS Huber, C Cook, P Bhattacharjee, AK TI Phase I study of detoxified Escherichia coli J5 lipopolysaccharide (J5dLPS)/group B meningococcal outer membrane protein (OMP) complex vaccine in human subjects SO VACCINE LA English DT Article DE vaccine; lipopolysaccharide; phase I study; sepsis; E. coli J5 ID GRAM-NEGATIVE BACTEREMIA; SEPTIC SHOCK; OPSONOPHAGOCYTIC ASSAY; SEVERE SEPSIS; DOUBLE-BLIND; ANTIBODY; POLYSACCHARIDE; TRIAL; IMMUNIZATION; RESPONSES AB We previously observed that a detoxified Escherichia coli O111, Re chemotype J5 lipopolysaccharide (J5dLPS)/group B meningococcal outer membrane protein (OMP) vaccine protected animals from experimental lethal sepsis when immune antibodies were given passively as treatment at the onset of fever or when vaccine was given actively as prophylaxis. To test the safety and immunogenicity of this vaccine, we administered doses of 5, 10 and 25 mug (based on dLPS) of vaccine at days 0, 28 and 56 to 24 human subjects (8 per group). Temperatures of 100.3, 99.5 and 99.4 degreesF occurred in three subjects. At 24 h, pain at the injection site was moderate in 38%, mild in 44% and not present in 18%, while at 48 h, it was 1, 25 and 73%, respectively. No alterations in baseline renal, hepatic or hematologic functions occurred. There were two to three times mean-fold increases in anti-J5dLPS IgG (range: 1.9-5.1) and IgM (range: 1.2-9.2) levels in subjects receiving the 10 and 25 mug doses. At 12-month follow-up, three of the original responders had continued elevation of antibody levels. A 25 mug booster dose of vaccine did not increase antibody levels among those responders and did not elicit antibodies among three subjects with no previous antibody response. The plasma from the six volunteers inhibited LPS-induced cytokine generation in human whole blood ex vivo. We conclude that this J5dLPS/OMP vaccine was safe and well-tolerated with transient, local pain at the injection site. Vaccine formulations with different adjuvants are currently under investigation. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Dept Med, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Walter Reed Army Inst Res, Dept Bacterial Dis, Div Communicable Dis & Immunol, Silver Spring, MD USA. Brown Univ, Mem Hosp Rhode Isl, Infect Dis Unit, Pawtucket, RI 02860 USA. RP Cross, AS (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, Dept Med, 685 W Baltimore St,HSF 480, Baltimore, MD 21201 USA. FU NIAID NIH HHS [R01AI42181-04] NR 25 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 7 PY 2003 VL 21 IS 31 BP 4576 EP 4587 DI 10.1016/S0264-410X(03)00483-3 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 747XG UT WOS:000186830900012 PM 14575770 ER PT J AU Yohrling, GJ Jiang, GCT DeJohn, MM Miller, DW Young, AB Vrana, KE Cha, JHJ AF Yohrling, GJ Jiang, GCT DeJohn, MM Miller, DW Young, AB Vrana, KE Cha, JHJ TI Analysis of cellular, transgenic and human models of Huntington's disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathology SO MOLECULAR BRAIN RESEARCH LA English DT Article DE tyrosine hydroxylase; Huntingtin; substantia nigra; Huntington's disease; dopamine; mRNA ID SUBUNIT MESSENGER-RNA; MOUSE MODEL; TRYPTOPHAN-HYDROXYLASE; TRANSCRIPTION FACTORS; PROJECTION NEURONS; EXPRESSION; DOPAMINE; GENE; MICE; BRAIN AB Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerativedisorder that is pathologically characterized by a striatal-specific degeneration. Aberrant dopamine neurotransmission has been proposed as a mechanism underlying the movement disorder of HD. We report that the enzymatic activity of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine biosynthesis, is decreased in a transgenic mouse model of HD. In addition, mutant huntingtin was found to disrupt transcription of TH and dopamine beta-hydroxylase (DbetaH) promoter reporter constructs. In situ hybridization revealed extensive loss of TH mRNA and decreased dopaminergic cell size in human HD substantia nigra. TH-immunoreactive protein was reduced in human grade 4 HD substantia nigra by 32% compared to age-matched controls. These findings implicate abnormalities in dopamine neuro transmission in HD and may provide new insights into targets for pharmacotherapy. (C) 2003 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp East, Dept Neurol, Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. Wake Forest Univ, Sch Med, Mol Genet Program, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp East, Dept Neurol, Ctr Aging Genet & Neurodegenerat, 114 16th St,B114-2000, Charlestown, MA 02129 USA. OI Vrana, Kent/0000-0003-4902-7733 NR 49 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV 6 PY 2003 VL 119 IS 1 BP 28 EP 36 DI 10.1016/j.molbrainres.2003.08.009 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 745CJ UT WOS:000186670700004 ER PT J AU Young, PJ Francis, JW Lince, D Coon, K Androphy, EJ Lorson, CL AF Young, PJ Francis, JW Lince, D Coon, K Androphy, EJ Lorson, CL TI The Ewing's sarcoma protein interacts with the Tudor domain of the survival motor neuron protein SO MOLECULAR BRAIN RESEARCH LA English DT Article DE survival motor neuron; spinal muscular atrophy; Tudor domain; arginine/glycine domain; Ewing's sarcoma; surface plasmon resonance ID SPINAL MUSCULAR-ATROPHY; DISEASE GENE-PRODUCT; RNA-POLYMERASE-II; SMN PROTEIN; BINDING-PROTEIN; ENZYMATIC METHYLATION; SINGLE NUCLEOTIDE; SELF-ASSOCIATION; COILED BODIES; COMPLEX AB The survival motor neuron (SMN) gene is the spinal muscular atrophy (SMA) determining gene. Here we report that the SMN protein product interacts in vitro and in vivo with the arginine/glycine (RG)-rich RNA binding protein and transcription factor, Ewing's sarcoma (EWS). Recently, the SMN encoded Tudor domain (exon 3) and the YG-motifs (exon 6) have been shown to be involved in binding to RG-rich proteins. Here, we demonstrate that the Tudor domain encoded by SMN exon 3 is independently sufficient to mediate the interaction with EWS. Synthetic mutations within the Tudor domain, as well as a SMA patient-derived mutation within exon 3, reduced the levels of the SMN/EWS interaction. Carboxyl-terminal SMN mutations that prevent formation of SMN oligomers also indirectly reduced EWS binding. A role for arginine methylation has been observed in some RG-containing SMN-interacting proteins. Here we demonstrate that SMN interacts with non-methylated EWS and an EWS-derived RG-containing peptide. In contrast to previously reported results, symmetrical dimethylation of the EWS-derived RG-peptide results in a quantitative increase in the dissociation rate between SMN and the symmetrical dimethylated EWS RG-peptide. Consistent with the interaction data, endogenous and transiently expressed SMN co-localizes with endogenous EWS in a number of cultured cell lines, as well as rat primary neuron cultures. Anti-sense RNA experiments, however, demonstrate that EWS does not mediate the nuclear distribution of SMN or other Cajal body components. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. Massachusetts Gen Hosp, Dept Pathol, Cecil B Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. Arizona State Univ, Dept Biol, Tempe, AZ 85287 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. RP Lorson, CL (reprint author), Univ Missouri, Dept Vet Pathobiol, 210 Connaway Hall, Columbia, MO 65211 USA. OI Androphy, Elliot/0000-0002-8104-0703 NR 60 TC 13 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV 6 PY 2003 VL 119 IS 1 BP 37 EP 49 DI 10.1016/j.molbrainres.2003.08.011 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 745CJ UT WOS:000186670700005 ER PT J AU Burstein, HJ AF Burstein, HJ TI Beyond tamoxifen - Extending endocrine treatment for early-stage breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID AROMATASE INHIBITORS; DRUG-THERAPY; TRIAL C1 Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. NR 11 TC 13 Z9 13 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 6 PY 2003 VL 349 IS 19 BP 1857 EP 1859 DI 10.1056/NEJMe038174 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 739NR UT WOS:000186353800013 PM 14551340 ER PT J AU Nathan, DG Wilson, JD AF Nathan, DG Wilson, JD TI Clinical research and the NIH - A report card SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACADEMIC HEALTH CENTERS; INSTITUTES-OF-HEALTH; MEDICAL-SCHOOLS; CHALLENGES; FUTURE C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 17 TC 51 Z9 52 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 NOV 6 PY 2003 VL 349 IS 19 BP 1860 EP 1865 DI 10.1056/NEJMsb035066 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 739NR UT WOS:000186353800014 PM 14602885 ER PT J AU Burger, M Glodek, A Hartmann, T Schmitt-Graff, A Silberstein, LE Fujii, N Kipps, TJ Burger, JA AF Burger, M Glodek, A Hartmann, T Schmitt-Graff, A Silberstein, LE Fujii, N Kipps, TJ Burger, JA TI Functional expression of CXCR4 (CD184) on small-cell lung cancer cells mediates migration, integrin activation, and adhesion to stromal cells SO ONCOGENE LA English DT Article DE chemokine receptor; lung cancer; signal transduction; integrin activation; adhesion; migration ID HEMATOPOIETIC PROGENITOR CELLS; CHEMOKINE RECEPTOR CXCR4; BONE-MARROW; FACTOR-I; TRANSENDOTHELIAL MIGRATION; SIGNAL-TRANSDUCTION; CD34(+) CELLS; STEM-CELLS; APOPTOSIS; VLA-4 AB Small-cell lung cancer (SCLC) is an aggressive, rapidly metastasizing neoplasm. The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is constitutively secreted by marrow stromal cells and plays a key role for homing of hematopoietic cells to the marrow. Here, we report that tumor cells from patients with SCLC express high levels of functional CXCR4 receptors for the chemokine CXCL12. Reverse transcriptase-polymerase chain reaction and flow cytometry demonstrated CXCR4 mRNA and CXCR4 surface expression in SCLC cell lines. Immunohistochemistry of primary tumor samples from SCLC patients revealed high expression of CXCR4. CXCL12 elicited CXCR4 receptor endocytosis, actin polymerization, and a robust activation of phospho-p44/42 mitogen-activated protein kinase in SCLC cells. Furthermore, CXCL12 induced SCLC cell invasion into extracellular matrix and firm adhesion to marrow stromal cells. Stromal cell adhesion of SCLC cells was significantly inhibited by the specific CXCR4 antagonist T140, pertussis toxin, antivascular cell adhesion molecule-1(VCAM-1) antibodies, and CS-1 peptide, demonstrating the importance of CXCR4 chemokine receptor activation and alpha4beta1 integrin binding, respectively. In addition, CXCL12 enhanced the adhesion of SCLC cells to immobilized VCAM-1, demonstrating that CXCR4 chemokine receptors can induce integrin activation on SCLC cells. As SCLC has a high propensity for bone marrow involvement, our findings suggest that CXCR4 chemokine receptors and alpha4beta1 integrins play a critical role in the interaction of SCLC cells with stromal cells in the tumor microenvironment. C1 Freiburg Univ Hosp, Dept Internal Med, Freiburg, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Freiburg Univ Hosp, Dept Pathol, Freiburg, Germany. Kyoto Univ, Grad Sch Pharmaceut Sci, Kyoto, Japan. Univ Calif San Diego, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA. RP Burger, JA (reprint author), Freiburg Univ Hosp, Dept Med, Div Hematol Oncol, Hugstetterstr 55, D-79106 Freiburg, Germany. RI Hartmann, Tanja Nicole/C-9345-2017 OI Hartmann, Tanja Nicole/0000-0002-2633-7301 NR 44 TC 175 Z9 182 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 6 PY 2003 VL 22 IS 50 BP 8093 EP 8101 DI 10.1038/sj.onc.1207097 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 740LG UT WOS:000186403400004 PM 14603250 ER PT J AU Cheng, LP Chen, CL Luo, P Tan, M Qiu, MS Johnson, R Ma, QF AF Cheng, LP Chen, CL Luo, P Tan, M Qiu, MS Johnson, R Ma, QF TI Lmx1b, Pet-1, and Nkx2.2 coordinately specify serotonergic neurotransmitter phenotype SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Lmx1b; Pet-1; Nkx2.2; serotonergic; neurotransmitter specification; brainstem ID CENTRAL-NERVOUS-SYSTEM; TRANSCRIPTION FACTOR; NEURON DEVELOPMENT; CELL FATE; EXPRESSION; GENE; CLONING; RAT; SPECIFICATION; TRANSPORTER AB Serotonergic (5-HT) neurons in the brainstem modulate a wide range of physiological processes and behaviors. Two transcription factor genes, Pet-1 and Nkx2.2, are necessary but not sufficient to specify the 5-HT transmitter phenotype. Here we show that the Lim class homeobox gene Lmx1b is required for proper formation of the entire 5-HT system in the hindbrain, as indicated by the loss of expression of genes necessary for serotonin synthesis and transport in Lmx1b null mice. Lmx1b and Pet1 act downstream of Nkx2.2, and their expression is independently regulated at the time when 5-HT transmitter phenotype is specified. Ectopic expression of Lmx1b plus Pet-1 is able to induce formation of 5-HT cells in the most ventral spinal cord, where Nkx2.2 is normally expressed. Combined expression of all three genes, Lmx1b, Pet-1, and Nkx2.2, drives 5-HT differentiation in the dorsal spinal cord. Our studies therefore define a molecular pathway necessary and sufficient to specify the serotonergic neurotransmitter phenotype. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Program Genes & Dev, Houston, TX 77030 USA. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, SM1022B,1 Jimmy Fund Way, Boston, MA 02115 USA. FU NIDCR NIH HHS [1 R01 DE13843-01] NR 44 TC 113 Z9 118 U1 2 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 5 PY 2003 VL 23 IS 31 BP 9961 EP 9967 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 741RZ UT WOS:000186474200001 PM 14602809 ER PT J AU Gibson, CM Pinto, DS Murphy, SA Morrow, DA Hobbach, HP Wiviott, SD Giugliano, RP Cannon, CP Antman, EM Braunwald, E AF Gibson, CM Pinto, DS Murphy, SA Morrow, DA Hobbach, HP Wiviott, SD Giugliano, RP Cannon, CP Antman, EM Braunwald, E CA TIMI Study Grp TI Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TIMI FRAME COUNT; TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE CORONARY SYNDROMES; ARTERY-BYPASS-SURGERY; RENAL-INSUFFICIENCY; CLINICAL OUTCOMES; TRIAL; THROMBOLYSIS; DYSFUNCTION; COMBINATION AB OBJECTIVES We hypothesized that impaired renal function would also be associated with poorer clinical outcomes among patients with ST-segment elevation myocardial infarction (STEMI) treated with fibrinolysis. BACKGROUND Previous studies have demonstrated that impaired renal function is associated with poorer clinical outcomes in the setting of unstable angina and non-STEMI and after percutaneous coronary intervention. METHODS Data were drawn from the Thrombolysis In Myocardial Infarction (TIMI)-10, TIMI-14, and Intravenous nPA for the Treatment of Infarcting Myocardium Early (InTIME-II) trials. RESULTS Within each TIMI risk score (TRS) for STEMI category (0 to 2, 3 to 4, greater than or equal to5), 30-day mortality increased stepwise among patients with normal (creatinine [Cr] less than or equal to1.2 mg/dl), mildly (Cr >1.2 to 2 mg/dl), and severely (Cr >2.0 mg/dl) impaired renal function (p < 0.001) and in patients with normal (creatinine clearance [CrCl] greater than or equal to90 ml/min), mildly (60 to <90 ml/min), moderately (30 to <60 ml/min), and severely (<30 ml/min) impaired CrCl (p < 0.001). Impaired renal function was associated with increased mortality after adjusting for previously identified correlates of mortality (using Cr: odds ratio [OR] for mild impairment 1.52, 95% confidence interval [CI] 1.30 to 1.77, p < 0.001; OR for severe impairment 3.73, 95% CI 2.55 to 5.45, p < 0.001; using CrCl: OR for mild impairment 1.38, 95% CI 1.10 to 1.73, p = 0.006; OR for moderate impairment 2.06, 95% CI 1.59 to 2.66, p < 0.001; OR for severe impairment 3.81, 95% CI 2.57 to 5.65, p < 0.001). CONCLUSIONS In the setting of STEMI, elevated Cr and/or impaired CrCl on presentation is associated with increased mortality, independent of other conventional risk factors and TRS. This association does not appear to be mediated by reduced fibrinolytic efficacy among patients with impaired renal function or by the presence of congestive heart failure on presentation. (C) 2003 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, Dept Med, TIMI Study Chairmans Off, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. St Marienkrankenhaus Siegen, Siegen, Germany. RP Gibson, CM (reprint author), TIMI Study Chairmans Off, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 26 TC 181 Z9 199 U1 0 U2 0 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 NOV 5 PY 2003 VL 42 IS 9 BP 1535 EP 1543 DI 10.1016/S0735-1097(03)01067-2 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 739LU UT WOS:000186348600001 PM 14607434 ER PT J AU Wenger, NS Solomon, DH Roth, CP MacLean, CH Saliba, D Kamberg, CJ Rubenstein, LZ Young, RT Sloss, EM Louie, R Adams, J Chang, JT Venus, PJ Schnelle, JF Shekelle, PG AF Wenger, NS Solomon, DH Roth, CP MacLean, CH Saliba, D Kamberg, CJ Rubenstein, LZ Young, RT Sloss, EM Louie, R Adams, J Chang, JT Venus, PJ Schnelle, JF Shekelle, PG TI The quality of medical care provided to vulnerable community-dwelling older patients SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; OF-CARE; PROJECT; ELDERS; BENEFICIARIES; IMPROVEMENT; OUTCOMES AB Background: Many people 65 years of age and older are at risk for functional decline and death. However, the resource-intensive medical care provided to this group has received little evaluation. Previous studies have focused on general medical conditions aimed at prolonging life, not on geriatric issues important for quality of life. Objective: To measure the quality of medical care provided to vulnerable elders by evaluating the process of care using Assessing Care of Vulnerable Elders quality indicators (Qls). Design: Observational cohort study. Setting: Managed care organizations in the northeastern and southwestern United States. Patients: Vulnerable older patients identified by a brief interview from a random sample of community-dwelling adults 65 years of age or older who were enrolled in 2 managed care organizations and received care between July 1998 and July 1999. Measurements: Percentage of 207 Qls passed, overall and for 22 target conditions; by domain of care (prevention, diagnosis, treatment, and follow-up); and by general medical condition (for example, diabetes and heart failure) or geriatric condition (for example, falls and incontinence). Results: Patients were eligible for 10 711 Qls, of which 55% were passed. There was no overall difference between managed care organizations. Wide variation in adherence was found among conditions, ranging from 9% for end-of-life care to 82% for stroke care. More treatment Qls were completed (81%) compared with other domains (follow-up, 63%; diagnosis, 46%; and prevention, 43%). Adherence to Qls was lower for geriatric conditions than for general medical conditions (31% vs. 52%; P < 0.001). Conclusions: Care for vulnerable elders falls short of acceptable levels for a wide variety of conditions. Care for geriatric conditions is much less optimal than care for general medical conditions. C1 RAND Corp, Hlth, Santa Monica, CA 90407 USA. RAND Corp, Hlth, Washington, DC USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Los Angeles Jewish Home Aging, Los Angeles, CA USA. Borun Ctr Gerontol Res, Los Angeles, CA USA. United Healthcare Corp, Ctr Hlth Care Policy & Evaluat, Minnetonka, MN USA. RP Wenger, NS (reprint author), RAND Corp, Hlth, 1700 Main St,M-26, Santa Monica, CA 90407 USA. NR 26 TC 236 Z9 237 U1 3 U2 10 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 NOV 4 PY 2003 VL 139 IS 9 BP 740 EP 747 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 738XJ UT WOS:000186312900004 PM 14597458 ER PT J AU van Zante, A Gauguet, JM Bistrup, A Tsay, D von Andrian, UH Rosen, SD AF van Zante, A Gauguet, JM Bistrup, A Tsay, D von Andrian, UH Rosen, SD TI Lymphocyte-HEV interactions in lymph nodes of a sulfotransferase-deficient mouse SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE lymphocyte homing; L-selectin; sulfotransferase; endothelium; MECA79 ID HIGH ENDOTHELIAL VENULES; L-SELECTIN LIGAND; P-SELECTIN; VASCULAR ADDRESSIN; BETA-2 INTEGRINS; SIALOMUCIN CD34; DISTINCT ROLES; T-LYMPHOCYTES; IN-SITU; GLYCAM-1 AB The interaction of L-selectin expressed on lymphocytes with sulfated sialomucin ligands such as CD34 and GlyCAM-1 on high endothelial venules (HEV) of lymph nodes results in lymphocyte rolling and is essential for lymphocyte recruitment. HEC-GlcNAc6ST-deficient mice lack an HEV-restricted sulfotransferase with selectivity for the C-6 position of N-acetylglucosamine (GlcNAc). HEC-GlcNAc6ST - / - animals exhibit faster lymphocyte rolling and reduced lyrnphocyte sticking in HEV, accounting for the diminished lymphocyte homing. Isolated CD34 and GlyCAM-1 from HEC-GlcNAc6ST-/- animals incorporate similar to70% less sulfate than ligands from wild-type animals. Furthermore, these ligands exhibit a comparable reduction of the epitope recognized by MECA79, a function-blocking antibody that reacts with L-selectin ligands in a GIcNAc-6-sulfate-dependent manner. Whereas MECA79 dramatically inhibits lymphocyte rolling and homing to lymph nodes in wild-type mice, it has no effect on HEC-GlcNAc6ST-/- mice. In contrast, in vitro rolling on purified GlyCAM-1 from HEC-GlcNAc6ST-/- mice, although greatly diminished compared with that on the wild-type ligand, is inhibited by MECA79. Our results demonstrate that HEC-GlcNAc6ST contributes predominantly, but not exclusively, to the sulfation of HEV ligands for L-selectin and that alternative, non-MECA79-reactive ligands are present in the absence of HEC-GlcNAc6ST. C1 Univ Calif San Francisco, Cardiovasc Res Inst, Program Immunol, Dept Anat, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res Inc, Boston, MA 02115 USA. RP Rosen, SD (reprint author), Univ Calif San Francisco, Box 0452, San Francisco, CA 94122 USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL54936, HL62524, R01 HL054936]; NIGMS NIH HHS [GM57411, R01 GM057411]; PHS HHS [R376M23547] NR 53 TC 29 Z9 32 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 3 PY 2003 VL 198 IS 9 BP 1289 EP 1300 DI 10.1084/jem.20030057 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 740VY UT WOS:000186423700002 PM 14597732 ER PT J AU M'Rini, C Cheng, GY Schweitzer, C Cavanagh, LL Palframan, RT Mempel, TR Warnock, RA Lowe, JB Quackenbush, EJ von Andrian, UH AF M'Rini, C Cheng, GY Schweitzer, C Cavanagh, LL Palframan, RT Mempel, TR Warnock, RA Lowe, JB Quackenbush, EJ von Andrian, UH TI A novel endothelial L-selectin ligand activity in lymph node medulla that is regulated by alpha(1,3)-fucosyltransferase-IV SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE homing; intravital microscopy; leukocyte adhesion; leukocyte rolling; vascular addressin ID P-SELECTIN; IN-VIVO; LEUKOCYTE ADHESION; VASCULAR ADDRESSIN; DEFICIENT MICE; FUCT-VII; VENULES; LYMPHOCYTES; RECRUITMENT; RECIRCULATION AB Lymphocytes home to peripheral lymph nodes (PLNs) via high endothelial venules (HEVs) in the subcortex and incrementally larger collecting venules in the medulla. HEVs express ligands for L-selectin, which mediates lymphocyte rolling. L-selectin counterreceptors in HEVs are recognized by rnAb MECA-79, a surrogate marker for molecularly heterogeneous glycans termed peripheral node addressin. By contrast, we find that medullary venules express L-selectin ligands not recognized by MECA-79. Both L-selectin ligands must be fucosylated by alpha(1,3)fucosyltransferase (FucT)-IV or FucT-VII as rolling is absent in FucT-IV+VII-/- mice. Intravital microscopy experiments revealed that MECA-79-reactive ligands depend primarily on FucT-VII, whereas MECA-79-independent medullary L-selectin ligands are regulated by FucT-IV. Expression levels of both enzymes paralleled these anatomical distinctions. The relative mRNA level of FucT-IV was higher in medullary venules than in HEVs, whereas FucT-VII was most prominent in HEVs and weak in medullary venules. Thus, two distinct L-selectin ligands are segmentally confined to contiguous microvascular domains in PLNs. Although MECA-79-reactive species predominate in HEVs, medullary venules express another ligand that is spatially, antigenically, and biosynthetic ally unique. Physiologic relevance for this novel activity in medullary microvessels is suggested by the finding that L-selectin-dependent T cell homing to PLNs was partly insensitive to MECA-79 inhibition. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pathol, Lab Immunol & Vasc Biol, Stanford, CA 94305 USA. Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Merck & Co Inc, Div Pharmacol, Merck Res Labs, Rahway, NJ 07065 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL48675, HL54936, HL56949, P01 HL048675, P01 HL056949, R01 HL054936] NR 51 TC 39 Z9 41 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 3 PY 2003 VL 198 IS 9 BP 1301 EP 1312 DI 10.1084/jem.20030182 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 740VY UT WOS:000186423700003 PM 14597733 ER PT J AU Dudley, DD Sekiguchi, J Zhu, CM Sadofsky, MJ Whitlow, S DeVido, J Monroe, RJ Bassing, CH Alt, FW AF Dudley, DD Sekiguchi, J Zhu, CM Sadofsky, MJ Whitlow, S DeVido, J Monroe, RJ Bassing, CH Alt, FW TI Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE antigen receptor; DNA cleavage; RS; hybrid joint; immune deficiency ID T-CELL-RECEPTOR; IMMUNOGLOBULIN GENE REARRANGEMENTS; HEAVY-CHAIN LOCUS; B-CELL; SIGNAL SEQUENCE; OMENN-SYNDROME; TERMINAL REGION; RAG PROTEINS; IN-VITRO; MUTATIONS AB RAG1 and RAG2 are the lymphocyte-specific components of the V(D)J recombinase. In vitro analyses of RAG function have relied on soluble, highly truncated "core" RAG proteins. To identify potential functions for noncore regions and assess functionality of core RAG1 in vivo, we generated core RAG1 knockin (RAG1(c/c)) mice. Significant B and T cell numbers are generated in RAG1(c/c) mice, showing that core RAG1, despite missing similar to40% of the RAG1 sequence, retains significant in vivo function. However, lymphocyte development and the overall level of V(D)J recombination are impaired at the progenitor stage in RAG1(c/c) mice. Correspondingly, there are reduced numbers of peripheral RAG1(c/c) B and T lymphocytes. Whereas normal B lymphocytes undergo rearrangement of both J(H) loci, substantial levels of germline J(H) loci persist in mature B cells of RAG1(c/c) mice, demonstrating that DJ(H) rearrangement on both IgH alleles is not required for developmental progression to the stage of V-H to DJ(H), recombination. Whereas V-H to DJ(H) rearrangements occur, albeit at reduced levels, on the nonselected alleles of RAG1(c/c) B cells that have undergone D to J(H) rearrangements, we do not detect V-H to D-H rearrangenients in RAG(c/c) B cells that retain germline J(H) alleles. We discuss the potential implications of these findings for noncore RAG1 functions and for the ordered assembly of V-H, D-H, and J(H) segments. C1 Harvard Univ, Childrens Hosp, Ctr Blood Res, Howard Hughes Med Inst, Boston, MA 02115 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Ctr Blood Res, Howard Hughes Med Inst, Enders Bldg,Rm 861, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NIAID NIH HHS [AI20047, P01 AI035714, R37 AI020047, AI35714, R01 AI020047] NR 63 TC 49 Z9 50 U1 1 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 NOV 3 PY 2003 VL 198 IS 9 BP 1439 EP 1450 DI 10.1084/jem.20030627 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 740VY UT WOS:000186423700015 PM 14581608 ER PT J AU Yun, SH Tearney, GJ de Boer, JF Iftimia, N Bouma, BE AF Yun, SH Tearney, GJ de Boer, JF Iftimia, N Bouma, BE TI High-speed optical frequency-domain imaging SO OPTICS EXPRESS LA English DT Article ID COHERENCE TOMOGRAPHY; REFLECTOMETRY; RESOLUTION; LASER AB We demonstrate high-speed, high-sensitivity, high-resolution optical imaging based on optical frequency-domain interferometry using a rapidly-tuned wavelength-swept laser. We derive and show experimentally that frequency-domain ranging provides a superior signal-to-noise ratio compared with conventional time-domain ranging as used in optical coherence tomography. A high sensitivity of - 110 dB was obtained with a 6 mW source at an axial resolution of 13.5 mum and an A-line rate of 15.7 kHz, representing more than an order-of-magnitude improvement compared with previous OCT and interferometric imaging methods. (C) 2003 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Blossom St,BAR-7, Boston, MA 02114 USA. EM syun@bics.bwh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCI NIH HHS [R01 CA103769, R01 CA103769-02] NR 23 TC 568 Z9 575 U1 3 U2 53 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD NOV 3 PY 2003 VL 11 IS 22 BP 2953 EP 2963 DI 10.1364/OE.11.002953 PG 11 WC Optics SC Optics GA 739JH UT WOS:000186341000020 PM 19471415 ER PT J AU Mortele, KJ Tuncali, K Cantisani, V Shankar, S vanSonnenberg, E Tempany, C Silverman, SG AF Mortele, KJ Tuncali, K Cantisani, V Shankar, S vanSonnenberg, E Tempany, C Silverman, SG TI MRI-guided abdominal intervention SO ABDOMINAL IMAGING LA English DT Review ID INTERSTITIAL LASER PHOTOCOAGULATION; PERCUTANEOUS ETHANOL INJECTION; INTENSITY FOCUSED ULTRASOUND; LOCALIZED PROSTATE-CANCER; MAGNETIC-RESONANCE; LIVER METASTASES; INDUCED THERMOTHERAPY; HEPATIC CRYOSURGERY; TRACKING CATHETER; IMAGING GUIDANCE C1 Brigham & Womens Hosp, Dept Radiol, Sect Abdominal Imaging & Intervent, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Mortele, KJ (reprint author), Brigham & Womens Hosp, Dept Radiol, Sect Abdominal Imaging & Intervent, 75 Francis St, Boston, MA 02115 USA. OI CANTISANI, VITO/0000-0003-1525-214X NR 84 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD NOV-DEC PY 2003 VL 28 IS 6 BP 756 EP 774 DI 10.1007/s00261-003-0048-4 PG 19 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 736ZQ UT WOS:000186204500001 PM 14753588 ER PT J AU Tamayo-Sarver, JH Dawson, NV Hinze, SW Cydulka, RK Wigton, RS Albert, JM Ibrahim, SA Baker, DW AF Tamayo-Sarver, JH Dawson, NV Hinze, SW Cydulka, RK Wigton, RS Albert, JM Ibrahim, SA Baker, DW TI The effect of race/ethnicity and desirable social characteristics on physicians' decisions to prescribe opioid analgesics SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE emergency department; analgesia prescription; race/ethnicity; usual source of care; communication; access ID IMPLICIT ASSOCIATION TEST; RHEUMATOID-ARTHRITIS; RACIAL-DIFFERENCES; AFRICAN-AMERICAN; PATIENT RACE; MANAGED-CARE; CANCER; PAIN; ETHNICITY; HEALTH AB Objective: Racial/ethnic disparities in physician treatment have been documented in multiple areas, including emergency department (ED) analgesia. The purpose of this study was to determine if physicians were predisposed to different treatment decisions based on patient race/ethnicity and if physicians' treatment predispositions changed when socially desirable information about the patient (occupation, socioeconomic status, and relationship with a primary care physician) was made explicit. Methods: The authors developed three clinical vignettes designed to engage physicians' decision-making processes. The patient's race/ethnicity was included. Each vignette randomly included or omitted explicit socially desirable information. The authors mailed 5,750 practicing emergency physicians three clinical vignettes and a one-page questionnaire about demographic and practice characteristics. Chi-square tests of significance for bivariate analyses and multiple logistic regression were used for multivariate analyses. Results: A total of 2,872 (53%) of the 5,398 potential physician subjects participated. Patient race/ethnicity had no effect on physician prescription of opioids at discharge for African Americans, Hispanics, and whites: absolute differences in rates of prescribing opioids at discharge were less than 2% for all three conditions presented. Making socially desirable information explicit increased the prescribing rates by 4% (95% CI = 0.1%, to 8%) for the migraine vignette and 6% (95% CI = 3% to 8%) for the back pain vignette. Conclusions: Patient race/ethnicity did not influence physicians' predispositions to treatment plans in clinical vignettes. Even knowing that the patient had a high-prestige occupation and a primary care provider only minimally increased prescribing of opioid analgesics for conditions with few objective findings. C1 Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Ctr Hlth Care Res & Policy, Metrohlth Med Ctr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Sociol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH 44106 USA. Univ Nebraska, Med Ctr, Coll Med, Dept Internal Med,Div Gen Internal Med, Omaha, NE 68182 USA. Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Div Gen Internal Med, Chicago, IL 60611 USA. RP Tamayo-Sarver, JH (reprint author), 4009 Cullen Dr, Cleveland, OH 44105 USA. NR 58 TC 65 Z9 66 U1 2 U2 6 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2003 VL 10 IS 11 BP 1239 EP 1248 DI 10.1197/S1069-6563903)00494-9 PG 10 WC Emergency Medicine SC Emergency Medicine GA 740WY UT WOS:000186426300014 PM 14597500 ER PT J AU Thrall, JH AF Thrall, JH TI Molecular Imaging and molecular biology SO ACADEMIC RADIOLOGY LA English DT Editorial Material ID IN-VIVO C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, MZ-FND 216,14 Fruit St, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2003 VL 10 IS 11 BP 1213 EP 1214 DI 10.1016/S1076-6332(03)00504-X PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 738VA UT WOS:000186307500001 PM 14626295 ER PT J AU Mendoza, RJ Pittenger, DJ AF Mendoza, RJ Pittenger, DJ TI Mental health services for patients with multiple sclerosis residing in long-term skilled nursing facilities: Problems and recommendations SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article ID MINIMUM DATA SET; HOME RESIDENTS; DEPRESSION C1 Boston Home, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Tennessee, Dept Psychol, Chattanooga, TN 37403 USA. RP Mendoza, RJ (reprint author), 65 Oak St, Newton, MA 02464 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD NOV PY 2003 VL 31 IS 2 BP 171 EP 180 DI 10.1023/B:APIH.0000003020.68713.89 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 756KK UT WOS:000187464100005 PM 14756198 ER PT J AU Kampov-Polevoy, AB Garbutt, JC Khalitov, E AF Kampov-Polevoy, AB Garbutt, JC Khalitov, E TI Family history of alcoholism and response to sweets SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE sweet taste; alcoholism; genetic marker ID PITUITARY BETA-ENDORPHIN; SACCHARIN INTAKE; ETHANOL-CONSUMPTION; TASTE PREFERENCES; NUCLEUS-ACCUMBENS; HEDONIC RESPONSE; WISTAR RATS; BODY-WEIGHT; DRINKING; SUCROSE AB Background: The relationship between a hedonic response to sweet tastes and a propensity to excessive alcohol drinking is supported by both animal and human studies. This study was designed to test the hypothesis that the genetic risk for alcoholism as measured by a paternal history of alcoholism in young social drinkers is associated with sweet-liking, defined as rating the strongest offered sucrose solution (i.e., 0.83 M) as the most palatable during the standard sweet test. Methods: Participants were 163 subjects (39% male) without a lifetime history of alcohol or drug abuse or dependence. Eighty-one subjects had a paternal history of alcoholism (FH+), and 82 did not (FH-). Each subject rated a series of sucrose solutions for intensity of sweetness and palatability. Subjects were categorized as sweet-likers if they rated the highest sucrose concentration as the most pleasurable. Results: The estimated odds of being a sweet-liker were 2.5 times higher for FH+ than for FH- subjects. FH+ subjects disliked the tastes of the two weakest offered sucrose concentrations (0.05 and 0.10 M), whereas FH- subjects reported these tastes to be neutral. Conclusions: The results of this study support the hypothesis that sweet-liking is associated with a genetic vulnerability to alcoholism. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Univ N Carolina, Ctr Alcohol Studies, Chapel Hill, NC USA. Univ Minnesota, Sch Stat, Minneapolis, MN 55455 USA. RP Kampov-Polevoy, AB (reprint author), Bronx Vet Affairs Med Ctr, Dept Psychiat, 536 OOMH,130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 68 TC 51 Z9 52 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2003 VL 27 IS 11 BP 1743 EP 1749 DI 10.1097/01.ALC.0000093739.05809.DD PG 7 WC Substance Abuse SC Substance Abuse GA 747TF UT WOS:000186820400007 PM 14634489 ER PT J AU Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S AF Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S CA Veterans Affairs Cooperative Study TI I. Veterans affairs cooperative study of polyenylphosphatidylcholine in alcoholic liver disease: Effects on drinking behavior by nurse/physician teams SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE brief invention; control of drinking ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; BRIEF PHYSICIAN ADVICE; UNITED-STATES; FOLLOW-UP; CIRRHOSIS; DRINKERS; FIBROSIS; TRIAL AB Background: This multicenter prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the effectiveness of polyenylphosphatidylcholine against the progression of liver fibrosis toward cirrhosis in alcoholics. Seven hundred eighty-nine alcoholics with an average intake of 16 drinks per day were enrolled. To control excessive drinking, patients were referred to a standard 12-step-based alcoholism treatment program, but most patients refused to attend. Accordingly, study follow-up procedures incorporated the essential features of the brief-intervention approach. An overall substantial and sustained reduction in drinking was observed. Hepatic histological and other findings are described in a companion article. Methods: Patients were randomized to receive daily three tablets of either polyenylphosphatidylcholine or placebo. Monthly follow-up visits included an extensive session with a medical nurse along with brief visits with a study physician (hepatologist or gastroenterologist). A detailed physical examination occurred every 6 months. In addition, telephone consultations with the nurse were readily available. All patients had a liver biopsy before entry; a repeat biopsy was scheduled at 24 and, 48 months. Results: There was a striking decrease in average daily alcohol intake to approximately 2.5 drinks per day. This was sustained over the course of the trial, lasting from 2 to 6 years. The effect was similar both in early dropouts and long-term patients, i.e., those with a 24-month biopsy or beyond. Conclusions: In a treatment trial of alcoholic liver fibrosis, a striking reduction in alcohol consumption from 16 to 2.5 daily drinks was achieved with a brief-intervention approach, which consisted of a relative economy of therapeutic efforts that relied mainly on treatment sessions with a medical nurse accompanied by shorter reinforcing visits with a physician. This approach deserves generalization to address the heavy drinking problems commonly encountered in primary care and medical specialty practices. C1 Bronx Vet Affairs Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, Bronx, NY USA. Univ Maryland, Sch Med, Perry Point Vet Affairs Med Ctr, Perry Point, MD USA. W Haven Vet Affairs Med Ctr, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. San Antonio Vet Affairs Med Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Lieber, CS (reprint author), VA Med Ctr, Alcohol Res Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 25 TC 42 Z9 43 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2003 VL 27 IS 11 BP 1757 EP 1764 DI 10.1097/01.ALC.0000093744.12232.34 PG 8 WC Substance Abuse SC Substance Abuse GA 747TF UT WOS:000186820400009 PM 14634491 ER PT J AU Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S AF Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S CA Veterans Affairs Cooperative Study TI II. Veterans affairs cooperative study of polyenylphosphatidylcholine in alcoholic liver disease SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases DE phospholipids; ascites; cirrhosis ID CHRONIC ETHANOL-CONSUMPTION; CHRONIC HEPATITIS-C; CLINICAL-TRIALS; FIBROSIS; CIRRHOSIS; LEVEL AB Background: Polyenylphosphatidylcholine (PPC) has been shown to prevent alcoholic cirrhosis in animals. Our aims were to determine the effectiveness of PPC in preventing or reversing liver fibrosis in heavy drinkers and to assess the extent of liver injury associated with the reduced drinking achieved in these patients. Methods: This randomized, prospective, double-blind, placebo-controlled clinical trial was conducted in 20 Veterans Affairs Medical Centers with 789 patients (97% male; mean age, 48.8 years) averaging 16 drinks per day (1 drink = 14 g of alcohol) for 19 years. A baseline liver biopsy confirmed the presence of perivenular or septal fibrosis or incomplete cirrhosis. They were randomly assigned either PPC or placebo. Liver biopsy was repeated at 24 months, and the main outcome measure was the stage of fibrosis compared with baseline. Progression was defined as advancing to a more severe stage. Results: The 2-year biopsy was completed in 412 patients. PPC did not differ significantly from placebo in its effect on the main outcome. Alcohol intake was unexpectedly reduced in both groups to approximately 2.5 drinks per day. With this intake, 21.4% advanced at least one stage (22.8% of PPC patients and 20.0% of placebo patients). The hepatitis C virus-positive subgroup exhibited accelerated progression. Improvement in transaminases and bilirubin favoring PPC was seen at some time points in other subgroups (hepatitis C virus-positive drinkers or heavy drinkers). Conclusions: PPC treatment for 2 years did not affect progression of liver fibrosis. A trend in favor of PPC was seen for transaminases and bilirubin (in subgroups). One of five patients progressed even at moderate levels of drinking, and thus health benefits commonly associated with moderate drinking do not necessarily extend to individuals in the early stages of alcoholic liver disease. C1 Bronx Vet Affairs Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, Bronx, NY USA. Univ Maryland, Sch Med, Perry Point Vet Affairs Med Ctr, Perry Point, MD USA. W Haven Vet Affairs Med Ctr, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. San Antonio Vet Affairs Med Ctr, San Antonio, TX USA. Hlth & Sci Ctr, San Antonio, TX 78285 USA. RP Lieber, CS (reprint author), VA Med Ctr, Alcohol Res Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 36 TC 66 Z9 74 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2003 VL 27 IS 11 BP 1765 EP 1772 DI 10.1097/01.ALC.0000093743.03049.80 PG 8 WC Substance Abuse SC Substance Abuse GA 747TF UT WOS:000186820400010 PM 14634492 ER PT J AU Morrow, DA AF Morrow, DA TI New insight into clinical risk scores for patients with acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID ELEVATION MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; PRISM-PLUS; TIMI; STRATIFICATION; MANAGEMENT; PROGNOSIS; UA/NSTEMI; TIROFIBAN; ISCHEMIA C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. NR 21 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2003 VL 146 IS 5 BP 754 EP 756 DI 10.1067/S0002-8703(03)00455-1 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 741ZW UT WOS:000186491100003 PM 14597922 ER PT J AU Januzzi, JL Cannon, CP Theroux, P Boden, WE AF Januzzi, JL Cannon, CP Theroux, P Boden, WE TI Optimizing glycoprotein IIb/IIIa receptor antagonist use for the non-ST-segment elevation acute coronary syndromes: Risk stratification and therapeutic intervention SO AMERICAN HEART JOURNAL LA English DT Article ID WAVE MYOCARDIAL-INFARCTION; REFRACTORY UNSTABLE ANGINA; PROSPECTIVE RANDOMIZED MULTICENTER; ISCHEMIC SYNDROME MANAGEMENT; PLACEBO-CONTROLLED TRIAL; TROPONIN-T; ARTERY DISEASE; PRISM-PLUS; CONSERVATIVE STRATEGIES; UNFRACTIONATED HEPARIN AB Despite extensive data supporting their use for non-ST-segment elevation acute coronary syndromes, glycoprotein (GP) IIb/IIIa antagonists are underutilized. This is likely the consequence of confusion as to which patients should receive these agents, as well as to the most appropriate timing and venue for their initiation. We will review the advances in the understanding of GP IIb/IIIa antagonist therapy, emphasizing methods of identifying those most likely to benefit from the use of GP IIb/IIIa receptor blockade. In addition, we will consider appropriate methods/venues for use of GP IIb/IIIa receptor antagonism, including its role in an "early invasive" catheterization strategy. C1 Hartford Hosp, Div Cardiol, Hartford, CT 06102 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. Montreal Heart Inst, Div Cardiol, Montreal, PQ H1T 1C8, Canada. RP Boden, WE (reprint author), Hartford Hosp, Div Cardiol, 80 Seymour St,Box 5037, Hartford, CT 06102 USA. NR 73 TC 10 Z9 10 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2003 VL 146 IS 5 BP 764 EP 774 DI 10.1067/S0002-8703(03)00437-X PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 741ZW UT WOS:000186491100005 PM 14597924 ER PT J AU Dieterich, DT Wasserman, R Brau, N Hassanein, TI Bini, EJ Bowers, PJ Sulkowski, MS AF Dieterich, DT Wasserman, R Brau, N Hassanein, TI Bini, EJ Bowers, PJ Sulkowski, MS TI Once-weekly epoetin alfa improves anemia and facilitates maintenance of ribavirin dosing in hepatitis C virus-infected patients receiving ribavirin plus interferon alfa SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week/102nd Annual Meeting of the American-Gastroenterological-Association CY MAY 20-23, 2001 CL ATLANTA, GEORGIA SP Amer Gastroenterol Assoc ID QUALITY-OF-LIFE; RANDOMIZED TRIAL; CHEMOTHERAPY PATIENTS; COMMUNITY ONCOLOGY; INITIAL TREATMENT; THERAPY; COMBINATION; DISEASE; CANCER; ERYTHROPOIETIN AB OBJECTIVE: The aim of this study was to determine the efficacy of epoetin alfa in alleviating anemia and minimizing ribavirin (RBV) dose reductions in patients with chronic hepatitis C virus (HCV) infection receiving combination RBV/interferon alfa (IFN) therapy. METHODS: HCV-infected patients who had Hb levels of 12 g/dl or less during the first 24 wk of combination RBV/IFN therapy (n = 64) were randomized to treatment with epoetin alfa (40,000 units) s.c. q.w. or to standard of care (SOC) for anemia management (RBV dose reduction or discontinuation, transfusions). Primary and secondary efficacy end-points were changes in Hb level and RBV dosage, respectively, from baseline to week 16 of epoetin alfa. therapy. RESULTS: Based on intent-to-treat analysis, the mean changes from baseline Hb levels at week 16 were +2.8 g/dl for epoetin alfa versus +0.4 g/dl for SOC (p < 0.0001), and the mean changes in RBV dosage were -34 mg/day for epoetin alfa versus -146 mg/day (p = 0.060) for SOC. The mean Hb level at week 16 in the epoetin alfa. group (13.8 g/dl) was significantly (p < 0.0001) higher than that of the SOC group (11.4 g/dl). At week 4 and subsequently, significantly more patients in the epoetin alfa group did not have RBV dosage reductions (p < 0.011). At study end, 83% of epoetin alfa-treated patients maintained RBV dosages of at least 800 mg/day, compared with 54% of patients receiving SOC (p = 0.022). Epoetin alfa was well tolerated. CONCLUSIONS: In anemic HCV-infected patients treated with RBV/IFN, epoetin alfa increases Hb levels and maintains RBV dosing. Based on these results, epoetin alfa seems to be promising in the treatment of HCV treatment-related anemia. Further research is warranted to determine the potential impact on outcomes, including quality of life and sustained viral response rate. (C) 2003 by Am. Coll. of Gastroenterology. C1 CUNY Mt Sinai Sch Med, Sch Med, Dept Med, New York, NY 10029 USA. New York VA Med Ctr, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Hepatitis Resource Ctr, Walnut Creek, CA USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Ortho Biotech Prod, Bridgewater, MA USA. Johns Hopkins Univ, Ctr Viral Hepatitis, Baltimore, MD USA. RP Dieterich, DT (reprint author), CUNY Mt Sinai Sch Med, Sch Med, Dept Med, Box 1118,1 Gustave L Levy Pl, New York, NY 10029 USA. NR 37 TC 143 Z9 145 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2003 VL 98 IS 11 BP 2491 EP 2499 DI 10.1016/j.amjgastroenterol.2003.08.006 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 746MQ UT WOS:000186750500025 PM 14638354 ER PT J AU Hiasa, Y Kamegaya, Y Nuriya, H Onji, M Kohara, M Schmidt, EV Chung, RT AF Hiasa, Y Kamegaya, Y Nuriya, H Onji, M Kohara, M Schmidt, EV Chung, RT TI Protein kinase R is increased and is functional in hepatitis C virus-related hepatocellular carcinoma SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NONSTRUCTURAL 5A PROTEIN; MALIGNANT-TRANSFORMATION; CELLULAR INHIBITOR; PKR; RNA; INTERFERON; ACTIVATION; CELLS; AMPLIFICATION; TRANSLATION AB OBJECTIVE: Protein kinase R (PKR) interacts with dsRNA and phosphorylates eukaryotic initiation factor-2 (eIF2alpha), which in turn inhibits host translation initiation as well as hepatitis C virus (HCV) translation. Because PKR inhibits host cell growth and proliferation, it has also been proposed to act as a eukaryotic tumor suppressor. To evaluate the role of PKR in HCV-related hepatocellular carcinoma (HCC), we compared PKR and related protein expression in paired tumor (T) and surrounding nontumor (NT) tissue. METHODS: Tissue samples were obtained from 12 HCV-infected HCCs. To determine PKR and related protein expression, Western blotting and semiquantitative reverse transcriptase-polymerase chain reaction were performed. RESULTS: PKR protein levels were consistently increased in HCV-related HCC compared with NT (p = 0.001); similar increases were seen in total eIF2alpha and the PKR inhibitor p58(IPK) in T compared with NT (p = 0.022, p = 0.048, respectively). Relative increases in phosphorylated eIF2alpha (peIF2alpha) were also seen, and the ratio of peIF2alpha/total eIF2alpha did not change in T compared with NT, suggesting that PKR remains functional within T. Cytoplasmic levels of HCV RNA within T were decreased compared with NT. CONCLUSIONS: These findings indicate that PKR has increased activity in human HCC compared with LC, and suggest that PKR acts as a growth inducer in HCC. (C) 2003 by Am. Coll. of Gastroenterology. C1 Massachusetts Gen Hosp, Hosp Children, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hosp Children, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Tokyo Metropolitan Inst Med Sci, Dept Microbiol & Cell Biol, Tokyo 113, Japan. Ehime Univ, Sch Med, Dept Internal Med 3, Matsuyama, Ehime 790, Japan. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Hosp Children, Gastrointestinal Unit, GRJ 825,55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI43478]; NIDDK NIH HHS [R01 DK57857] NR 35 TC 21 Z9 23 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 NOV PY 2003 VL 98 IS 11 BP 2528 EP 2534 DI 10.1016/S0002-9270(03)01696-4 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 746MQ UT WOS:000186750500030 PM 14638359 ER PT J AU Goodgame, B Shaheen, NJ Galanko, J El-Serag, HB AF Goodgame, B Shaheen, NJ Galanko, J El-Serag, HB TI The risk of end stage liver disease and hepatocellular carcinoma among persons infected with hepatitis C virus: Publication bias? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NON-B-HEPATITIS; TERM FOLLOW-UP; SINGLE-SOURCE OUTBREAK; NON-A; NATURAL-HISTORY; POSTTRANSFUSION HEPATITIS; IMMUNE GLOBULIN; ITALIAN PATIENTS; COHORT; TRANSFUSION AB OBJECTIVES: In persons infected with hepatitis C virus (HCV), the incidence of cirrhosis and hepatocellular carcinoma (HCC) can be estimated by examining over time entire cohorts with known onset of HCV infection. We performed a systematic review of the literature to identify and to analyze studies that examine such cohorts. METHODS: A search of all articles from 1980 to 2001 was performed. Published studies were included in which chronic HCV infection was defined by elevation of liver enzymes or persistent RNA. We excluded studies in which cohorts were selected from patients with prevalent liver disease or in whom the onset of infection could not be estimated. Two investigators abstracted the data. The incidences of cirrhosis and HCC were analyzed in all studies and in categories based on study design, mode of HCV acquisition, sample size and duration of follow-up, age at the onset of infection, and the quality of estimating the onset of HCV infection. RESULTS: Of the articles, 21 fulfilled the selection criteria. Studies varied in sample size (17-1,680), duration of follow-up (8-45 yr), total person-years (157-34,098), and the mean age at onset of HCV (5-58 yr). The mean time to end stage liver disease (ESLD) was 4-23 yr and to HCC was 9-31 yr. A funnel plot showed a possible publication bias against studies with low incidence of ESLD and HCC. The pooled weighted incidence rates for ESLD and HCC based on infection mode were as follows: community-acquired HCV, 1.9 and 0 per 1,000 person-years; transfusion associated, 4.5 and 0.7; hemophilia patients, 7.9 and 1.0; anti-D IgG, 0.7 and 0 per 1,000 person-years. Poisson regression modeling showed that the incidence of ESLD is increased in studies with a low quality estimate of the onset of HCV infection, in community-acquired and transfusion-associated HCV, and in studies with prospective design. CONCLUSIONS: We found large variation in the incidence estimates of cirrhosis and HCC. Short duration of follow-up, small sample size, and possible publication bias may explain some of this variation. Low quality estimates of the onset of HCV infection, a prospective study design, and a transfusion- or hemophilia-related mode of acquisition were independent predictors of high reported incidence of ESLD. (C) 2003 by Am. Coll. of Gastroenterology. C1 Houston Vet Affairs Med Ctr 152, Gastroenterol Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr 152, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ N Carolina, Div Digest Dis, Chapel Hill, NC 27515 USA. Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27515 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Shaheen, Nicholas/A-1898-2013 FU NIDDK NIH HHS [P30DK34987, K23DK59311-01] NR 55 TC 23 Z9 24 U1 0 U2 2 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 NOV PY 2003 VL 98 IS 11 BP 2535 EP 2542 DI 10.1016/S0002-9270(03)00663-4 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 746MQ UT WOS:000186750500031 PM 14638360 ER PT J AU Otto, E Schermer, B Obara, T O'Toole, JF Landau, D Goodship, JA Strachan, T Antignac, C Walz, G Drummond, IA Benzing, T Hildebrandt, F AF Otto, E Schermer, B Obara, T O'Toole, JF Landau, D Goodship, JA Strachan, T Antignac, C Walz, G Drummond, IA Benzing, T Hildebrandt, F TI Mutations in Inversin cause Nephronophthisis type 2, linking cystic kidney disease to the function of primary cilia and left-right axis determination. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Michigan, Dept Ped, Ann Arbor, MI 48109 USA. Univ Hosp, Renal Div, Freiberg, Germany. Univ Hosp, Ctr Clin Res, Freiberg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA USA. Soroka Med Ctr, Dept Ped, IL-84101 Beer Sheva, Israel. Univ Newcastle, Inst Human Genet, Int Ctr Life, Newcastle Upon Tyne, Tyne & Wear, England. Ren Descartes Univ, Necker Hosp, INSERM, U574, Paris, France. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RI Schermer, Bernhard/E-9972-2014 OI Schermer, Bernhard/0000-0002-5194-9000 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 3 BP 162 EP 162 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700003 ER PT J AU Slaugenhaupt, S Mull, J Leyne, M Gill, S Hims, M Cuajungco, M Reed, R Gusella, J AF Slaugenhaupt, S Mull, J Leyne, M Gill, S Hims, M Cuajungco, M Reed, R Gusella, J TI Can drugs enhance mRNA splicing efficiency in human genetic disease? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet 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 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 NOV PY 2003 VL 73 IS 5 MA 98 BP 181 EP 181 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700100 ER PT J AU Gabriel, SB Patterson, N Reich, DE Lochner, A McDonald, G Moore, JM Roy, J Shaffner, SF Daly, MJ Altshuler, D AF Gabriel, SB Patterson, N Reich, DE Lochner, A McDonald, G Moore, JM Roy, J Shaffner, SF Daly, MJ Altshuler, D TI A survey of the genomic background of low frequency SNPs. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Whitehead Inst, Ctr Genome Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 123 BP 186 EP 186 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700123 ER PT J AU Scacheri, PC Rozenblatt-Rosen, O Caplen, N Wolfsberg, T Meyerson, M Collins, FS AF Scacheri, PC Rozenblatt-Rosen, O Caplen, N Wolfsberg, T Meyerson, M Collins, FS TI WARNING: siRNAs can induce off-target effects in mammalian cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV PY 2003 VL 73 IS 5 MA 230 BP 207 EP 207 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700231 ER PT J AU Herbert, A Liu, C Karamohamed, S Liu, S Wilson, PWF Meigs, JA Cupples, LA AF Herbert, A Liu, C Karamohamed, S Liu, S Wilson, PWF Meigs, JA Cupples, LA TI Body mass index modifies the association of interleukin 6 genotype with insulin resistance in men: the Framingham Offspring Study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study Genet Lab, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Gen Med Div, Gen Internal Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gen Med Div, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 240 BP 209 EP 209 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700241 ER PT J AU Comeau, A Parad, R Dorkin, H Dovey, M Haver, K Lapey, A Gerstle, R O'Sullivan, B AF Comeau, A Parad, R Dorkin, H Dovey, M Haver, K Lapey, A Gerstle, R O'Sullivan, B TI Increased sensitivity at the cost of increased referrals when population-based newborn screening incorporates testing for multiple mutations (MM): Cystic fibrosis (CF) newborn screening (NBS) as a model SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Massachusetts, Sch Med, New England Newborn Screening Program, Amherst, MA 01003 USA. New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Baystate Med Ctr, Springfield, MA USA. Univ Massachusetts, Worcester, MA 01605 USA. RI Parad, Richard/E-8559-2010 NR 0 TC 0 Z9 0 U1 0 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 NOV PY 2003 VL 73 IS 5 MA 256 BP 213 EP 213 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700259 ER PT J AU Lee, C Drandi, D Dal Cin, P Gribben, J AF Lee, C Drandi, D Dal Cin, P Gribben, J TI Prognostic markers in CLL by array-based comparative genomic hybridization. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI drandi, daniela/Q-6504-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 283 BP 218 EP 218 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700283 ER PT J AU Phelan, CM Lubinski, J Ghadirian, P Lynch, HT Garbers, J Weber, B Horsman, D Aube, J Sun, P Narod, S AF Phelan, CM Lubinski, J Ghadirian, P Lynch, HT Garbers, J Weber, B Horsman, D Aube, J Sun, P Narod, S TI Cancer variation associated with the position of BRCA2 gene mutation SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Ctr Res Womens Hlth, Toronto, ON, Canada. Pomeranian Acad Med, Hered Canc Ctr, Szczecin, Poland. CHUM, Hotel Dieu, Unite Rech, Montreal, PQ, Canada. Creighton Univ, Omaha, NE 68178 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. BC Canc Agcy, Vancouver, BC, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 413 BP 240 EP 240 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700412 ER PT J AU Wei, MJ Dignam, J Sveen, L Fackenthal, J Taniguchi, T Hagos, F D'Andrea, AD Olopade, OI AF Wei, MJ Dignam, J Sveen, L Fackenthal, J Taniguchi, T Hagos, F D'Andrea, AD Olopade, OI TI FANCF promoter is methylated in human sporadic breast cancers. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 471 BP 250 EP 250 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700471 ER PT J AU Leach, NT Bruns, GAP Eisenman, R Ferguson, HL Gusella, JF Harris, DJ Herrick, SR Higgins, AW Kim, HG Ligon, AH Lu, W Maas, RL Michaud, S Michelson, AM Moore, SD Peters, RE Quade, BJ Quintero-Rivera, F Williamson, RE Morton, CC AF Leach, NT Bruns, GAP Eisenman, R Ferguson, HL Gusella, JF Harris, DJ Herrick, SR Higgins, AW Kim, HG Ligon, AH Lu, W Maas, RL Michaud, S Michelson, AM Moore, SD Peters, RE Quade, BJ Quintero-Rivera, F Williamson, RE Morton, CC TI Developmental Genome Anatomy Project (DGAP): Identification of genes involved in human development. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 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 NOV PY 2003 VL 73 IS 5 MA 795 BP 306 EP 306 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700796 ER PT J AU Gao, H Espinola, J MacDonald, ME AF Gao, H Espinola, J MacDonald, ME TI CLN6 encodes linclin, a novel 28kD transmembrane protein. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Harvard Univ, Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 1016 BP 344 EP 344 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701017 ER PT J AU Grody, W Ogino, S AF Grody, W Ogino, S TI Generalized Bayesian risk calculations for autosomal recessive disease when only one mutation is detected, incorporating test sensitivity and each parent's ethnicity information: what if a fetus has echogenic bowel and one detectable CFTR mutation? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 1100 BP 358 EP 358 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701102 ER PT J AU Wilson, R Ogino, S AF Wilson, R Ogino, S TI Accurate carrier risk calculations for autosomal recessive disorders. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Penn, Pathol Lab Med, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 1106 BP 359 EP 359 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701108 ER PT J AU Moscarillo, T Go, R Holt, H Goldberg, S Chaglassian, A Stoler, J Blacker, D AF Moscarillo, T Go, R Holt, H Goldberg, S Chaglassian, A Stoler, J Blacker, D TI Genetic knowledge arid attitudes among individuals at risk for Alzheimer's disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Alabama, Birmingham, AL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 1120 BP 361 EP 361 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701121 ER PT J AU Ogino, S AF Ogino, S TI Frequencies of normal and disease SMN1 alleles, SMN1-SMN2 haplotypes, and de novo SMN1 mutations: implications in SMA genetic risk assessment and molecular evolution of SMN. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 NOV PY 2003 VL 73 IS 5 MA 1312 BP 394 EP 394 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701311 ER PT J AU Hennigan, A Hayes, L Tatis, M Sisson, J Greenough, K Kertiles, L Gallardo, E Illa, I Brown, RH Batish, SD Seltzer, WK AF Hennigan, A Hayes, L Tatis, M Sisson, J Greenough, K Kertiles, L Gallardo, E Illa, I Brown, RH Batish, SD Seltzer, WK TI A blood based diagnostic test for LGMD 2B and Miyoshi Myopathy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Athena Diagnost Inc, Worcester, MA 01605 USA. Hosp Santa Cruz & San Pablo, Dept Neurol, E-08025 Barcelona, Spain. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 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 NOV PY 2003 VL 73 IS 5 MA 1416 BP 412 EP 412 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701419 ER PT J AU Perry, RT Wiener, H Harrell, LE Blacker, D Tanzi, RE McInnis, M Bassett, SS Go, RCP AF Perry, RT Wiener, H Harrell, LE Blacker, D Tanzi, RE McInnis, M Bassett, SS Go, RCP TI Association of polymorphisms in MTHFR and TGF beta 1 in Alzheimer's disease patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Alabama, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Charleston, MA USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 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 NOV PY 2003 VL 73 IS 5 MA 1764 BP 471 EP 471 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701767 ER PT J AU Skol, AD Faraone, SV Tsuang, DW Bingham, S Young, KA Haverstock, SL Mena, F Menon, AS Sautter, F Vanden Eng, JL Keith, T Boehnke, M Tsuang, MT Schellenberg, GD AF Skol, AD Faraone, SV Tsuang, DW Bingham, S Young, KA Haverstock, SL Mena, F Menon, AS Sautter, F Vanden Eng, JL Keith, T Boehnke, M Tsuang, MT Schellenberg, GD TI A genome-wide linkage scan for schizophrenia in veterans affairs cooperative study families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Massachusetts Mental Hlth Ctr, Harvard Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Genet, Boston, MA USA. Genome Therapeut Inc, Waltham, MA USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 1828 BP 481 EP 481 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701829 ER PT J AU Moore, JM Blumenstiel, B Chanoux, R Defelice, M Faggart, M Goyette, M Lochner, A Nguyen, H Stahl, E Winchester, E Ziaugra, L Altshuler, D Gabriel, SB AF Moore, JM Blumenstiel, B Chanoux, R Defelice, M Faggart, M Goyette, M Lochner, A Nguyen, H Stahl, E Winchester, E Ziaugra, L Altshuler, D Gabriel, SB TI SNP genotyping production for the WICGR Hap Map project. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Whitehead Inst, Ctr Genome Res, Cambridge, MA 02142 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 0 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 NOV PY 2003 VL 73 IS 5 MA 1835 BP 483 EP 483 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701836 ER PT J AU Butler, J Bretsky, P Haiman, C Stram, DO Pike, MC Lunetta, KL Ardlie, KG Henderson, BE Daly, MJ Altshuler, D Hirschhorn, JN AF Butler, J Bretsky, P Haiman, C Stram, DO Pike, MC Lunetta, KL Ardlie, KG Henderson, BE Daly, MJ Altshuler, D Hirschhorn, JN TI Haplotype structure of ESR1 and association studies with complex traits. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. USC, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Genom Collaborat, Cambridge, MA USA. MIT Ctr Genome Res, Cambridge, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 0 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 NOV PY 2003 VL 73 IS 5 MA 1863 BP 487 EP 487 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701862 ER PT J AU Li, JL Hayden, M Almqvist, EW Durr, A Dod, C Morrison, PJ Suchowersky, O Ross, CA Margolis, RL Gmez-Tortosa, E Mayo, D Novelletto, A Nance, M Trent, RJA Zanko, A Abramson, RK Russ, AL Gusella, JF MacDonald, ME Myers, RH AF Li, JL Hayden, M Almqvist, EW Durr, A Dod, C Morrison, PJ Suchowersky, O Ross, CA Margolis, RL Gmez-Tortosa, E Mayo, D Novelletto, A Nance, M Trent, RJA Zanko, A Abramson, RK Russ, AL Gusella, JF MacDonald, ME Myers, RH TI A genome scan for modifiers of age at onset in Huntington's disease: The HD MAPS study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Bioinformat Program, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. RI Ross, Christopher/H-8395-2013; Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 1891 BP 492 EP 492 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701891 ER PT J AU Yang, RX Kelley, MJ McMaster, M Liebsch, NJ Bergen, AW Beerman, M Haque, K Goldstein, AM Parry, DM AF Yang, RX Kelley, MJ McMaster, M Liebsch, NJ Bergen, AW Beerman, M Haque, K Goldstein, AM Parry, DM TI Genetic heterogeneity in familial chordoma SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, DHHS, Dept DCEG, NIH, Rockville, MD USA. Duke Univ, Dept Med, Durham, NC USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. NCI, DHHS, CGF, NIH, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 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 NOV PY 2003 VL 73 IS 5 MA 1908 BP 495 EP 495 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701911 ER PT J AU Graham, FL Allingham, RR Hauser, M LaRocque-Abramson, K Santiago, CM Ventura, A DelBono, E Shi, JR Haines, JL Wiggs, JL Pericak-Vance, MA AF Graham, FL Allingham, RR Hauser, M LaRocque-Abramson, K Santiago, CM Ventura, A DelBono, E Shi, JR Haines, JL Wiggs, JL Pericak-Vance, MA TI Evidence for linkage but not association to the GABRB3 region of chromosome 15 in a subset of primary open angle glacoma (POAG) families SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Duke Univ, Ctr Med, Durham, NC USA. Vanderbilt Univ, Nashville, TN USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 1923 BP 497 EP 497 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701922 ER PT J AU Santangelo, SL Book, K Yen, CH Seddon, JM AF Santangelo, SL Book, K Yen, CH Seddon, JM TI A genome-wide scan for age-related macular degeneration provides evidence for linkage to several chromosomal regions including significant linkage to chromosomes 2,3,6, and 8 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 1946 BP 501 EP 501 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701948 ER PT J AU Walter, JW Allingham, RR Flor, JD Abramson, KR Graham, FL Cohen, CS Santiago, C del Bono, EA Auguste, J Rogers, K Haines, JL Pericak-Vance, MA Wiggs, JL Hauser, MA AF Walter, JW Allingham, RR Flor, JD Abramson, KR Graham, FL Cohen, CS Santiago, C del Bono, EA Auguste, J Rogers, K Haines, JL Pericak-Vance, MA Wiggs, JL Hauser, MA TI Optineurin sequence variants do not contribute to high-tension primary open-angle glaucoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Duke Univ, Durham, NC USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 NOV PY 2003 VL 73 IS 5 MA 1975 BP 506 EP 506 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701975 ER PT J AU Paschou, P Pakstis, AJ Speed, WC DeMille, MMC Kidd, JR Ruggeri, V Kurlan, R Pauls, DL Kidd, KK AF Paschou, P Pakstis, AJ Speed, WC DeMille, MMC Kidd, JR Ruggeri, V Kurlan, R Pauls, DL Kidd, KK TI Fine mapping of 17q25 supports linkage with Gilles de la Tourette Syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14627 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 2149 BP 535 EP 535 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702148 ER PT J AU Abramson, KR Hauser, MA Marks, OA Santiago, C Graham, FL del Bono, EA Pericak-Vance, MA Wiggs, JL Haines, JL Allingham, RR AF Abramson, KR Hauser, MA Marks, OA Santiago, C Graham, FL del Bono, EA Pericak-Vance, MA Wiggs, JL Haines, JL Allingham, RR TI Investigating candidate genes and novel ESTS in primary open angle glaucoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Vanderbilt Univ, Nashville, TN USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 2189 BP 542 EP 542 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702189 ER PT J AU Leyne, M Nesta, F Dai, D Acierno, J Freed, L Levine, R Slaugenhaupt, S AF Leyne, M Nesta, F Dai, D Acierno, J Freed, L Levine, R Slaugenhaupt, S TI Examination of the mitral valve prolapse locus on chromosome 11p15.4. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Harvard Inst Human Genet, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 73 IS 5 MA 2272 BP 556 EP 556 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702272 ER PT J AU Hims, MM Leyne, M Ibrahim, E Mull, J Gill, SP Reed, R Slaugenhaupt, SA AF Hims, MM Leyne, M Ibrahim, E Mull, J Gill, SP Reed, R Slaugenhaupt, SA TI The introduction of exonic splice enhancer elements improves axon inclusion in familial dysautonomia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 NOV PY 2003 VL 73 IS 5 MA 2442 BP 584 EP 584 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702441 ER PT J AU Sharon, D Sandberg, MA Rabe, VW Stillberger, M Dryja, TP Berson, EL AF Sharon, D Sandberg, MA Rabe, VW Stillberger, M Dryja, TP Berson, EL TI RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NUCLEOTIDE-EXCHANGE FACTOR; NORTH-AMERICAN COHORT; EXON ORF15; POSITIONAL CLONING; GENE; FAMILIES; LOCUS; IDENTIFICATION; DEGENERATION; DYSTROPHY AB We determined the mutation spectrum of the RP2 and RPGR genes in patients with X-linked retinitis pigmentosa (XLRP) and searched for correlations between categories of mutation and severity of disease. We screened 187 unrelated male patients for mutations, including 135 with a prior clinical diagnosis of XLRP, 11 with probable XLRP, 30 isolate cases suspected of having XLRP, and 11 with cone-rod degeneration. Mutation screening was performed by single-strand conformation analysis and by sequencing of all RP2 exons and RPGR exons 1-14, ORF15, and 15a. The refractive error, visual acuity, final dark-adapted threshold, visual field area, and 30-Hz cone electroretinogram (ERG) amplitude were measured in each patient. Among the 187 patients, we found 10 mutations in RP2, 2 of which are novel, and 80 mutations in RPGR, 41 of which are novel; 66% of the RPGR mutations were within ORF15. Among the 135 with a prior clinical diagnosis of XLRP, mutations in the RP2 and RPGR genes were found in 9 of 135 (6.7%) and 98 of 135 (72.6%), respectively, for a total of 79% of patients. Patients with RP2 mutations had, on average, lower visual acuity but similar visual field area, final dark-adapted threshold, and 30-Hz ERG amplitude compared with those with RPGR mutations. Among patients with RPGR mutations, those with ORF15 mutations had, on average, a significantly larger visual field area and a borderline larger ERG amplitude than did patients with RPGR mutations in exons 1-14. Among patients with ORF15 mutations, regression analyses showed that the final dark-adapted threshold became lower (i.e., closer to normal) and that the 30-Hz ERG amplitude increased as the length of the wild-type ORF15 amino acid sequence increased. Furthermore, as the length of the abnormal amino acid sequence following ORF15 frameshift mutations increased, the severity of disease increased. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. RP Berson, EL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. RI Sharon, Dror/P-4539-2015 OI Sharon, Dror/0000-0002-1789-5811 FU NEI NIH HHS [EY08683, EY00169, R01 EY000169, R01 EY008683, R37 EY000169] NR 36 TC 105 Z9 110 U1 3 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 NOV PY 2003 VL 73 IS 5 BP 1131 EP 1146 DI 10.1086/379379 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 742AR UT WOS:000186493400014 PM 14564670 ER PT J AU Bond, J Scott, S Hampshire, DJ Springell, K Corry, P Abramowicz, MJ Mochida, GH Hennekam, RCM Maher, ER Fryns, JP Alswaid, A Jafri, H Rashid, Y Mubaidin, A Walsh, CA Roberts, E Woods, CG AF Bond, J Scott, S Hampshire, DJ Springell, K Corry, P Abramowicz, MJ Mochida, GH Hennekam, RCM Maher, ER Fryns, JP Alswaid, A Jafri, H Rashid, Y Mubaidin, A Walsh, CA Roberts, E Woods, CG TI Protein-truncating mutations in ASPM cause variable reduction in brain size SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RECESSIVE MICROCEPHALY MAPS; ABNORMAL SPINDLE; MITOTIC SPINDLE; LOCUS; DROSOPHILA; GENE AB Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common cause of human autosomal recessive primary microcephaly (MCPH), a condition in which there is a failure of normal fetal brain development, resulting in congenital microcephaly and mental retardation. We have performed the first comprehensive mutation screen of the 10.4-kb ASPM gene, identifying all 19 mutations in a cohort of 23 consanguineous families. Mutations occurred throughout the ASPM gene and were all predicted to be protein truncating. Phenotypic variation in the 51 affected individuals occurred in the degree of microcephaly (5-11 SDs below normal) and of mental retardation (mild to severe) but appeared independent of mutation position. C1 Univ Leeds, St James Hosp, Mol Med Unit, Leeds LS9 7TF, W Yorkshire, England. Univ Leeds, St James Hosp, Dept Clin Genet, Leeds LS9 7TF, W Yorkshire, England. St Lukes Hosp, Dept Pediat, Bradford BD5 0NA, W Yorkshire, England. Free Univ Brussels, Hop Erasme, B-1070 Brussels, Belgium. Med Genet Lab, Brussels, Belgium. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Harvard Inst Med,Dept Neurol,Div Neurogenet, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. Univ Amsterdam, Acad Med Ctr, Dept Pediat, NL-1105 AZ Amsterdam, Netherlands. Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med Mol Genet, Birmingham, W Midlands, England. Univ Hosp Gasthuisberg, Ctr Human Genet, B-3000 Louvain, Belgium. Riyadh Armed Forces Hosp, Riyadh, Saudi Arabia. King Hussein Med Ctr, Dept Neurol, Amman, Jordan. RP Bond, J (reprint author), Univ Leeds, St James Hosp, Mol Med Unit, Beckett St, Leeds LS9 7TF, W Yorkshire, England. RI woods, christopher/A-1361-2010; MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 20 TC 87 Z9 93 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 NOV PY 2003 VL 73 IS 5 BP 1170 EP 1177 DI 10.1086/379085 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 742AR UT WOS:000186493400018 PM 14574646 ER PT J AU Zhou, XP Marsh, DJ Morrison, CD Chaudhury, AR Maxwell, M Reifenberger, G Eng, C AF Zhou, XP Marsh, DJ Morrison, CD Chaudhury, AR Maxwell, M Reifenberger, G Eng, C TI Germline inactivation of PTEN and dysregulation of the phosphoinositol-3-kinase/Akt pathway cause human Lhermitte-Duclos disease in adults SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet ID CELL-CYCLE ARREST; GENOTYPE-PHENOTYPE CORRELATIONS; BANNAYAN-ZONANA-SYNDROME; TUMOR-SUPPRESSOR PTEN; BREAST-CANCER MODEL; COWDEN-DISEASE; PHOSPHATASE-ACTIVITY; MUTATION SPECTRUM; PTEN/MMAC1 GENE; SOMA SIZE AB Lhermitte-Duclos disease (LDD), or dysplastic gangliocytoma of the cerebellum, is an unusual hamartomatous overgrowth disorder. LDD can be familial or, more commonly, sporadic. It has been only recently recognized that LDD may be associated with Cowden syndrome (CS). Over 80% of patients with CS carry germline mutations in PTEN. It remains unclear whether all cases of LDD, even without features of CS, are caused by germline PTEN mutation and whether somatic PTEN mutation occurs in sporadic LDD. We obtained paraffin-embedded LDD lesions from 18 unselected, unrelated patients and performed mutational analysis of PTEN. Overall, 15 (83%) of 18 samples were found to carry a PTEN mutation. All individuals with mutations were adult-onset patients, but the three without mutations were diagnosed at the ages of 1, 3, and 11 years. Germline DNA was available from six adult-onset cases, and all had germline PTEN mutations. Of these six, two had CS features, one did not have CS features, and three were of unknown CS status. Immunohistochemistry revealed that 75% of the LDD samples had complete or partial loss of PTEN expression accompanied by elevated phosphorylated Akt, specifically in the dysplastic gangliocytoma cells. These data suggest that the loss of PTEN function is sufficient to cause LDD. The high frequency and spectrum of germline PTEN mutations in patients ascertaining by LDD alone confirm that LDD is an important defining feature of CS. Individuals with LDD, even without apparent CS features, should be counseled as in CS. C1 Ohio State Univ, Human Canc Genet Program, Ctr Comprehens Canc,Div Human Canc Genet, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Ohio State Univ, Clin Canc Genet Program, Ctr Comprehens Canc,Div Human Canc Genet, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Dept Adult Oncol, Translat Res Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA USA. Royal N Shore Hosp, Kolling Inst Med Res, Canc Genet Lab, Sydney, NSW, Australia. Univ Sydney, Dept Mol Med, Sydney, NSW 2006, Australia. Univ Dusseldorf, Inst Neuropathol, D-4000 Dusseldorf, Germany. Univ Cambridge, Human Canc Genet Res Grp, Canc Res UK, Cambridge CB2 1TN, England. RP Eng, C (reprint author), Ohio State Univ, Human Canc Genet Program, Ctr Comprehens Canc,Div Human Canc Genet, Dept Mol Virol Immunol & Med Genet, 420 W 12th Ave,Suite 690 TMRF, Columbus, OH 43210 USA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [P30 CA016058, P30CA16058] NR 47 TC 82 Z9 91 U1 0 U2 5 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 NOV PY 2003 VL 73 IS 5 BP 1191 EP 1198 DI 10.1086/379382 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 742AR UT WOS:000186493400020 PM 14566704 ER PT J AU Kim, JY Hauser, R Wand, MP Herrick, RF Houk, RS Aeschliman, DB Woodin, MA Christiani, DC AF Kim, JY Hauser, R Wand, MP Herrick, RF Houk, RS Aeschliman, DB Woodin, MA Christiani, DC TI Association of expired nitric oxide with urinary metal concentrations in boilermakers exposed to residual oil fly ash SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE biological monitoring; metals; air pollutants; occupational; nitric oxide; epidemiology ID OCCUPATIONAL CHRONIC EXPOSURE; STAINLESS-STEEL WELDERS; FUEL-OIL; LUNG INJURY; AIRWAY INFLAMMATION; MASS-SPECTROMETRY; TRANSITION-METALS; WORKERS; CHROMIUM; VANADIUM AB Background Exposure to metal-containing particulate matter has been associated with adverse pulmonary responses. Metals in particulate matter are soluble, hence are readily recovered in urine of exposed individuals. This study investigated the association between urinary metal concentrations and the fractional concentration of expired nitric oxide (FENO) in boilermakers (N = 32) exposed to residual oil fly ash (ROFA). Methods Subjects were monitored at a boiler overhaul site located in the New England area, USA. FENO and urine samples were collected pre- and post-workshift for 5 consecutive workdays. Metals investigated included vanadium (V), chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), and lead (Pb). Results The median FENO was 7.5 ppb (95% CI: 7.4-8.0), and the median creatinine-adjusted urinary metal concentrations (mug/g creatinine) were: vanadium, 1.37; chromium, 0.48; manganese, 0.30; nickel, 1.52; copper, 3.70; and lead, 2.32. Linear mixed-effects models indicated significant inverse exposure-response relationships between log FENO and the log-transformed urinary concentrations of vanadium, manganese, nickel, copper, and lead at several lag times, after adjusting for smoking status. Conclusions Urine samples may be utilized as a biomarker of occupational metal exposure. The inverse association between FENO and urinary metal concentrations suggests that exposure to metals in particulate matter may have an adverse effect on respiratory health. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Iowa State Univ, US Dept Energy, Dept Chem, Ames Lab, Ames, IA 50011 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1402, Boston, MA 02115 USA. RI Wand, Matt /F-9413-2012 OI Wand, Matt /0000-0003-2555-896X FU NIEHS NIH HHS [ES00002, ES09860]; NIOSH CDC HHS [OH00152]; PHS HHS [T42110421, T3206709] NR 40 TC 2 Z9 2 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2003 VL 44 IS 5 BP 458 EP 466 DI 10.1002/ajim.10305 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 742NE UT WOS:000186523300002 PM 14571509 ER PT J AU McKinley, LL Moriarty, HJ Short, TH Johnson, CC AF McKinley, LL Moriarty, HJ Short, TH Johnson, CC TI Effect of comparative data feedback on intensive care unit infection rates in a Veterans Administration Hospital Network System SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article ID WOUND-INFECTION; SURVEILLANCE; STATES AB Background: Infection control surveillance is not performed with standardized methodology within the Veterans Affairs (VA) health system. The purposes of this study were (1) to provide network hospitals with a standardized intensive care unit (ICU) surveillance system developed by the Centers for Disease Control and Prevention (CDC); (2) to compare ICU infection rates in hospitals that receive comparative data with those that do not; and (3) to compare network device-associated infection trends to national trends. Methods: One VA Medical Center served as the central coordination site where surveillance data were analyzed with CDC's criteria and reported back to the sites. During 1999, the experimental group received risk-adjusted infection rates with national comparative data, and the control group received only risk-adjusted infection rates without comparative data. In 2000, hospitals in both groups received risk-adjusted infection rates accompanied by national data. Results: In 1999, the device-associated infection rates were significantly higher in the control group compared with the experimental group. In the control group, the device-associated infection rates were significantly higher than the national comparative CDC rates; in the experimental group, the device-associated infection rates were not significantly different from the national comparative CDC rates. In 2000, the control group device-associated infection rates were not significantly different from the experimental group. The observed rates in both groups were not significantly different from the CDC rates. Conclusions: Study results suggest that infection rate outcomes may be reduced when national comparative data are provided. The study may serve as an infection control surveillance model for VA hospital networks. C1 Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. Vet Affairs Med Ctr, Patient Care Serv, Philadelphia, PA USA. Indiana Univ Penn, Indiana, PA USA. RP McKinley, LL (reprint author), VA Med Ctr, Dept Med, 2500 Overlake Terrace, Madison, WI 53705 USA. NR 20 TC 8 Z9 9 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD NOV PY 2003 VL 31 IS 7 BP 397 EP 404 DI 10.1067/mic.2003.46 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 742LU UT WOS:000186519700003 PM 14639435 ER PT J AU Saha, S Hickam, DH AF Saha, S Hickam, DH TI Explaining low ratings of patient satisfaction among Asian-Americans SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE Asian-Americans; ethnic groups; minority groups; patient satisfaction ID PRIMARY-CARE PERFORMANCE; HEALTH-CARE; QUALITY; SERVICES; VISITS AB Asian-Americans report lower levels of satisfaction with health care than other racial or ethnic groups. To determine potential reasons for this observation, we analyzed data from a national household telephone survey examining various aspects of health and health care across racial or ethnic groups. As in previous studies, Asians reported lower satisfaction with their physicians and health care services than other racial or ethnic groups, even after adjusting for demographic and health-related variables. However, Asians also reported lower satisfaction with their health insurance and with life in general and were less likely than non-Asians to have changed physicians due to dissatisfaction. We conclude that lower satisfaction ratings among Asians may be due to different response tendencies rather than to differences in quality of care. Further research is needed to explain this phenomenon and assess its potential impact on quality-of-care evaluations for clinicians and health care organizations providing care for large numbers of Asian-Americans. C1 Oregon Hlth & Sci Univ, Gen Internal Med Sect, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Hlth Serv Res & Dev Serv, Portland Vet Affairs Med Ctr, Div Gen Internal Med & Geriatr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. RP Saha, S (reprint author), Oregon Hlth & Sci Univ, Gen Internal Med Sect, P3MED,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 24 TC 16 Z9 16 U1 0 U2 0 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD NOV-DEC PY 2003 VL 18 IS 6 BP 256 EP 264 DI 10.1177/106286060301800606 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 752JD UT WOS:000187156600006 PM 14738037 ER PT J AU Lawrence, VA AF Lawrence, VA TI The relation between postoperative cardiac and noncardiac complications: Pathophysiological dominoes or doubles tennis? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID SURGERY; OUTCOMES; STAY C1 Univ Texas, Hlth Sci Ctr, Div Gen Med, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, Div Gen Med, San Antonio, TX 78229 USA. VERDICT, Audie Murphy Div, Div Gen Med, San Antonio, TX 78229 USA. RP Lawrence, VA (reprint author), Univ Texas, Hlth Sci Ctr, Div Gen Med, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM vlawrence@uthscsa.edu NR 7 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 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 2003 VL 115 IS 7 BP 580 EP 581 DI 10.1016/S0002-9343(03)00553-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 740PX UT WOS:000186411700012 PM 14599640 ER PT J AU Freitas, FRS Moriscot, AS Jorgetti, V Soares, AG Passarelli, M Scanlan, TS Brent, GA Bianco, AC Gouveia, CHA AF Freitas, FRS Moriscot, AS Jorgetti, V Soares, AG Passarelli, M Scanlan, TS Brent, GA Bianco, AC Gouveia, CHA TI Spared bone mass in rats treated with thyroid hormone receptor TR beta-selective compound GC-1 SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE thyrotoxicosis; osteopenia; osteoporosis; bone mineral density; bone histomorphometry ID GROWTH-FACTOR-I; BIOCHEMICAL MARKERS; MINERAL METABOLISM; MICE; EXPRESSION; ALPHA-1; TISSUE; HYPERTHYROIDISM; RESISTANCE; PHENOTYPE AB Thyrotoxicosis is frequently associated with increased bone turnover and decreased bone mass. To investigate the role of thyroid hormone receptor-beta (TRbeta) in mediating the osteopenic effects of triiodothyronine (T-3), female adult rats were treated daily ( 64 days) with GC-1 (1.5 mug/100 g body wt), a TRbeta-selective thyromimetic compound. Bone mass was studied by dual-energy X-ray absorptiometry of several skeletal sites and histomorphometry of distal femur, and the results were compared with T-3-treated (3 mug/100 g body wt) or control animals. As expected, treatment with T-3 significantly reduced bone mineral density (BMD) in the lumbar vertebrae (L-2-L-5), femur, and tibia by 10-15%. In contrast, GC-1 treatment did not affect the BMD in any of the skeletal sites studied. The efficacy of GC-1 treatment was verified by a reduction in serum TSH (-52% vs. control, P < 0.05) and cholesterol (-21% vs. control, P < 0.05). The histomorphometric analysis of the distal femur indicated that T-3 but not GC-1 treatment reduced the trabecular volume, thickness, and number. We conclude that chronic, selective activation of the TRbeta isoform does not result in bone loss typical of T-3-induced thyrotoxicosis, suggesting that the TRbeta isoform is not critical in this process. In addition, our findings suggest that the development of TR-selective T-3 analogs that spare bone mass represents a significant improvement toward long-term TSH-suppressive therapy. C1 Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508900 Sao Paulo, Brazil. Univ Sao Paulo, Inst Biomed Sci, Dept Histol, BR-05508900 Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, BR-05508900 Sao Paulo, Brazil. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Los Angeles, CA 91301 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 91301 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 91301 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Thyroid Div, Boston, MA 02115 USA. RP Gouveia, CHA (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof Lineu Prestes 2415,Rm 114, BR-05508900 Sao Paulo, Brazil. RI Bianco, Antonio/A-4965-2008; Moriscot, Anselmo/C-4506-2012; Moriscot, Anselmo/H-6985-2012; Freitas, Fatima/I-5678-2012; Soares, Antonio/C-9179-2016; JORGETTI, VANDA/C-9470-2012 OI Bianco, Antonio/0000-0001-7737-6813; Soares, Antonio/0000-0001-5814-3475; JORGETTI, VANDA/0000-0002-4824-8879 NR 39 TC 43 Z9 49 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV 1 PY 2003 VL 285 IS 5 BP E1135 EP E1141 DI 10.1152/ajpendo.00506.2002 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 730HB UT WOS:000185822500025 PM 12965872 ER PT J AU Klerman, EB Adler, GK Jin, MS Maliszewski, AM Brown, EN AF Klerman, EB Adler, GK Jin, MS Maliszewski, AM Brown, EN TI A statistical model of diurnal variation in human growth hormone SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE compartment model; constant routine ID GH-RELEASING HORMONE; ULTRASENSITIVE CHEMILUMINESCENCE ASSAY; METABOLIC-CLEARANCE; SECRETION; SOMATOSTATIN; PITUITARY; PULSATILE; RECEPTOR; TIME; BASAL AB The diurnal pattern of growth hormone (GH) serum levels depends on the frequency and amplitude of GH secretory events, the kinetics of GH infusion into and clearance from the circulation, and the feedback of GH on its secretion. We present a two-dimensional linear differential equation model based on these physiological principles to describe GH diurnal patterns. The model characterizes the onset times of the secretory events, the secretory event amplitudes, as well as the infusion, clearance, and feedback half-lives of GH. We illustrate the model by using maximum likelihood methods to fit it to GH measurements collected in 12 normal, healthy women during 8 h of scheduled sleep and a 16-h circadian constant-routine protocol. We assess the importance of the model components by using parameter standard error estimates and Akaike's Information Criterion. During sleep, both the median infusion and clearance half-life estimates were 13.8 min, and the median number of secretory events was 2. During the constant routine, the median infusion half-life estimate was 12.6 min, the median clearance half-life estimate was 11.7 min, and the median number of secretory events was 5. The infusion and clearance half-life estimates and the number of secretory events are consistent with current published reports. Our model gave an excellent fit to each GH data series. Our analysis paradigm suggests an approach to decomposing GH diurnal patterns that can be used to characterize the physiological properties of this hormone under normal and pathological conditions. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Sleep Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med,Massachusetts Gen Hosp, MIT,Div Hlth Sci & Technol, Dept Anesthesia & Crit Care,Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Klerman, EB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Sleep Med, 221 Longwood Ave, Boston, MA 02115 USA. RI Jin, Moonsoo/D-6128-2011 FU NCRR NIH HHS [M01-RR-20635, M01 RR002635]; NIA NIH HHS [K01 AG000661, P01 AG009975, K01 AG000661-05, K01-AG-00661]; NIAMS NIH HHS [R01-AR-43130, R01 AR043130]; NIGMS NIH HHS [R01-GM-53559]; NIMH NIH HHS [K02-MH-61637] NR 40 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV 1 PY 2003 VL 285 IS 5 BP E1118 EP E1126 DI 10.1152/ajpendo.00562.2002 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 730HB UT WOS:000185822500023 PM 12888486 ER PT J AU Levin, BE Dunn-Meynell, AA Ricci, MR Cummings, DE AF Levin, BE Dunn-Meynell, AA Ricci, MR Cummings, DE TI Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE ghrelin receptor; arcuate nucleus; dorsomedial nucleus; ventromedial nucleus; leptin receptor ID DIET-INDUCED OBESITY; GROWTH-HORMONE SECRETAGOGUE; SPRAGUE-DAWLEY RATS; FOOD-INTAKE; ARCUATE NUCLEUS; CIRCULATING GHRELIN; INSULIN-RESISTANCE; ACYLATED PEPTIDE; NEUROPEPTIDE-Y; NERVOUS-SYSTEM AB Rats selectively bred to develop diet-induced obesity (DIO) spontaneously gain more body weight between 5 and 7 wk of age than do those bred to be diet resistant (DR). Here, chow-fed DIO rats ate 9% more and gained 19% more body weight from 5 to 6 wk of age than did DR rats but had comparable leptin and insulin levels. However, 6-wk-old DIO rats had 29% lower plasma ghrelin levels at dark onset but equivalent levels 6 h later compared with DR rats. When subsequently fed a high-energy (HE; 31% fat) diet for 10 days, DIO rats ate 70% more, gained more body and adipose depot weight, had higher leptin and insulin levels, and had 22% lower feed efficiency than DR rats fed HE diet. In DIO rats on HE diet, leptin levels increased significantly at 3 days followed by increased insulin levels at 7 days. These altered DIO leptin and ghrelin responses were associated with 10% lower leptin receptor mRNA expression in the arcuate (ARC), dorsomedial (DMN), and ventromedial hypothalamic nuclei and 13 and 15% lower ghrelin receptor (GHS-R) mRNA expression in the ARC and DMN than in the DR rats. These data suggest that increased ghrelin signaling is not a proximate cause of DIO, whereas reduced leptin sensitivity might play a causal role. C1 Dept Vet Affairs Med Ctr, Serv Neurol, E Orange, NJ 07018 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurosci, Newark, NJ 07103 USA. Res Diets Inc, New Brunswick, NJ 08901 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Endocrine, Seattle, WA 98108 USA. RP Levin, BE (reprint author), Vet Affairs Med Ctr, Neurol Serv 127C, 385 Tremont Ave, E Orange, NJ 07018 USA. FU NIDDK NIH HHS [R01 DK-30066, DK-61516, F32 DK-59682] NR 51 TC 92 Z9 95 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV 1 PY 2003 VL 285 IS 5 BP E949 EP E957 DI 10.1152/ajpendo.00186.2003 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 730HB UT WOS:000185822500003 PM 12865257 ER PT J AU Mundinger, TO Mei, Q Figlewicz, DP Lernmark, A Taborsky, GJ AF Mundinger, TO Mei, Q Figlewicz, DP Lernmark, A Taborsky, GJ TI Impaired glucagon response to sympathetic nerve stimulation in the BB diabetic rat: effect of early sympathetic islet neuropathy SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE norepinephrine; 6-hydroxydopamine; neuropathy ID INSULIN-INDUCED HYPOGLYCEMIA; NOREPINEPHRINE SPILLOVER; EPINEPHRINE SECRETION; AUTONOMIC NEUROPATHY; PANCREATIC GLUCAGON; STRUCTURAL-CHANGES; CELL ACTIVITY; SYSTEM; SOMATOSTATIN; ACTIVATION AB We investigated the functional impact of a recently described islet-specific loss of sympathetic nerves that occurs soon after the autoimmune destruction of beta-cells in the BB diabetic rat (35). We found that the portal venous (PV) glucagon response to sympathetic nerve stimulation (SNS) was markedly impaired in newly diabetic BB rats ( BB D). We next found a normal glucagon response to intravenous epinephrine in BB D, eliminating the possibility of a generalized secretory defect of the BB D alpha-cell as the mediator of the impaired glucagon response to SNS. We then sought to determine whether the glucagon impairment to SNS in BB D was due solely to their loss of islet sympathetic nerve terminals or whether other effects of autoimmune diabetes contributed. We therefore reproduced, in nondiabetic Wistar rats, an islet nerve terminal loss similar to that in BB D with systemic administration of the sympathetic neurotoxin 6-hydroxydopamine. The impairment of the glucagon response to SNS in these chemically denervated, nondiabetic rats was similar to that in the spontaneously denervated BB D. We conclude that the early sympathetic islet neuropathy of BB D causes a functional defect of the sympathetic pathway to the alpha-cell that can, by itself, account for the impaired glucagon response to postganglionic SNS. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Mundinger, TO (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, 1660 S Columbian Wy, Seattle, WA 98108 USA. FU NIAID NIH HHS [AI-42380]; NIDDK NIH HHS [DK-12829, DK-50154, DK-12047] NR 46 TC 20 Z9 20 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV 1 PY 2003 VL 285 IS 5 BP E1047 EP E1054 DI 10.1152/ajpendo.00136.2003 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 730HB UT WOS:000185822500014 PM 12876072 ER PT J AU Sakamoto, K Aschenbach, WG Hirshman, MF Goodyear, LJ AF Sakamoto, K Aschenbach, WG Hirshman, MF Goodyear, LJ TI Akt signaling in skeletal muscle: regulation by exercise and passive stretch SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE contraction; fiber type; glycogen synthase kinase-3; glycogen synthase ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; PHOSPHOINOSITIDE 3-KINASE; GLUCOSE-TRANSPORT; PHOSPHATIDYLINOSITOL 3-KINASE; OXIDATIVE STRESS; CARDIAC MYOCYTES; INSULIN; PHOSPHORYLATION; CONTRACTION AB Akt/protein kinase B is a serine/threonine kinase that has emerged as a critical signaling component for mediating numerous cellular responses. Contractile activity has recently been demonstrated to stimulate Akt signaling in skeletal muscle. Whether physiological exercise in vivo activates Akt is controversial, and the initiating factors that result in the stimulation of Akt during contractile activity are unknown. In the current study, we demonstrate that treadmill running exercise of rats using two different protocols ( intermediate high or high-intensity exhaustive exercise) significantly increases Akt activity and phosphorylation in skeletal muscle composed of various fiber types. To determine if Akt activation during contractile activity is triggered by mechanical forces applied to the skeletal muscle, isolated skeletal muscles were incubated and passively stretched. Passive stretch for 10 min significantly increased Akt activity (2-fold) in the fast-twitch extensor digitorum longus (EDL) muscle. However, stretch had no effect on Akt in the slow-twitch soleus muscle, although there was a robust phosphorylation of the stress-activated protein kinase p38. Similar to contraction, stretch-induced Akt activation in the EDL was fully inhibited in the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin, whereas glycogen synthase kinase-3 (GSK3) phosphorylation was only partially inhibited. Stretch did not cause dephosphorylation of glycogen synthase on GSK3-targeted sites in the absence or presence of wortmannin. We conclude that physiological exercise in vivo activates Akt in multiple skeletal muscle fiber types and that mechanical tension may be a part of the mechanism by which contraction activates Akt in fast-twitch muscles. C1 Joslin Diabet Ctr, Div Res, Metab Sect, 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, Yokohama, Kanagawa 232, Japan. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, Metab Sect, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR-42238, AR-45670]; NIDDK NIH HHS [DK-59769] NR 49 TC 112 Z9 118 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV 1 PY 2003 VL 285 IS 5 BP E1081 EP E1088 DI 10.1152/ajpendo.00228.2003 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 730HB UT WOS:000185822500018 PM 12837666 ER PT J AU Derose, SF Asch, SM Fielding, JE Schuster, MA AF Derose, SF Asch, SM Fielding, JE Schuster, MA TI Developing quality indicators for local health departments - Experience in Los Angeles County SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PERFORMANCE; CARE AB Objectives: To develop public health quality indicators for local health department (LHD) use. Methods: An indicator development team utilized public health quality measurement concepts, reviewed existing quality measurement-related initiatives, and conducted interviews with LHD staff in order to identify and develop quality indicators for the Los Angeles County Health Department. Results: Sixty-one recommended and 50 acceptable (i.e., scientifically sound but less useful) indicators were developed, with an emphasis on measuring process quality in services delivery. Pre-existing indicators from external sources, when available, were often not well suited to the Health Department's needs. The indicator development process clarified conceptual issues, highlighted strengths and limitations of potential indicators, and revealed implementation barriers. Conclusions: A limited number of generally available, quantitative indicators of local public health quality exist. Indicators addressing the delivery of LHD services can be locally developed to fill an important gap in public health quality-improvement efforts. However, implementation of quality measurement is difficult due to limited evidence on public health practices, sparse data resources, unclear accountability, and inconsistent organizational motivation. C1 So Calif Kaiser Permanente, Dept Res & Evaluat, Pasadena, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Cty Los Angeles Dept Hlth Serv, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Cty Los Angeles Dept Hlth Serv, Dept Hlth Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Cty Los Angeles Dept Hlth Serv, Dept Pediat, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Derose, SF (reprint author), 393 E Walnut St,991, Pasadena, CA 91188 USA. FU ODCDC CDC HHS [U48/CCU 915773] NR 40 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2003 VL 25 IS 4 BP 347 EP 357 DI 10.1016/S0749-3797(03)00208-3 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 734HC UT WOS:000186048300014 PM 14580639 ER PT J AU Geller, DA Biederman, J Stewart, SE Mullin, B Martin, A Spencer, T Faraone, SV AF Geller, DA Biederman, J Stewart, SE Mullin, B Martin, A Spencer, T Faraone, SV TI Which SSRI? A meta-analysis of pharmacotherapy trials in pediatric obsessive-compulsive disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the American-Academy-of-Child-and-Adolescent-Psychiatry CY OCT 22-27, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Child & Adolescent Psychiat ID DOUBLE-BLIND; TOURETTES-SYNDROME; CLOMIPRAMINE TREATMENT; MULTICENTER TRIAL; CLINICAL-TRIALS; TIC DISORDER; CHILDREN; ADOLESCENTS; FLUOXETINE; PLACEBO AB Objective: The authors conducted a meta-analysis of published randomized, controlled medication trials in children and adolescents with obsessive-compulsive disorder (OCD) to assess evidence for differential efficacy based on type of drug, study design, and outcome measure. Method: A systematic literature search was performed for articles pertaining to the pharmacological treatment of pediatric and/or adolescent OCD. All baseline, posttreatment, and change scores with standard deviations reported in each study were included in the analyses. Effect sizes for dependent measures were expressed as standardized mean differences. The analysis included data on efficacy for four selective serotonin reuptake inhibitors (SSRIs) (paroxetine, fluoxetine, fluvoxamine, and sertraline) and clomipramine, four study designs, four dependent outcome measures, and two types of outcome scores (change and posttreatment scores). Multivariate regression was performed to assess the degree to which the effect sizes varied with the methodological features of each study. Results: Twelve studies with a total of 1,044 participants met all inclusion criteria for the analysis. The pooled standardized mean difference for the results of all studies was 0.46 and showed a highly significant difference between drug and placebo treatment. Only one of the four outcome measures evaluated was not sensitive to change with treatment. A multivariate regression analysis of drug effect with other variables controlled showed that clomipramine was significantly superior to each of the SSRIs but that the SSRIs were comparably effective. Conclusions: Although highly significant, the overall effect sizes for medication were modest. Similarities and differences between the variables studied that emerged in the meta-analysis may have implications for both clinical care and future research. C1 Massachusetts Gen Hosp, Pediat OCD Program, Clin & Res Program Pediat Psychol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Pediat OCD Program, Clin & Res Program Pediat Psychol, WACC 725,15 Parkham St, Boston, MA 02114 USA. RI Stewart, Evelyn/K-6961-2014; OI Faraone, Stephen/0000-0002-9217-3982; Stewart, S. Evelyn/0000-0002-0994-6383 FU NIMH NIH HHS [MH 01792, MH 01481] NR 34 TC 184 Z9 188 U1 1 U2 20 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2003 VL 160 IS 11 BP 1919 EP 1928 DI 10.1176/appi.ajp.160.11.1919 PG 10 WC Psychiatry SC Psychiatry GA 740PB UT WOS:000186409800003 PM 14594734 ER PT J AU Ouellette, H Thomas, BJ Torriani, M AF Ouellette, H Thomas, BJ Torriani, M TI Using dynamic sonography to diagnose extensor digitorum brevis manus SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID HAND; WRIST C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 15 Parkman St,WACC 515, Boston, MA 02114 USA. NR 8 TC 10 Z9 10 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 NOV PY 2003 VL 181 IS 5 BP 1224 EP 1226 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 735RY UT WOS:000186129400022 PM 14573408 ER PT J AU Yeh, ED AF Yeh, ED TI Characterization of breast lesions with proton MR Spectroscopy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yeh, ED (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, ACC 219,15 Parkman St, Boston, MA 02114 USA. NR 5 TC 4 Z9 6 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 NOV PY 2003 VL 181 IS 5 BP 1273 EP 1274 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 735RY UT WOS:000186129400032 PM 14573419 ER PT J AU Ptak, T Sheridan, RL Rhea, JT Gervasini, AA Yun, JH Curran, MA Borszuk, P Petrovick, L Novelline, RA AF Ptak, T Sheridan, RL Rhea, JT Gervasini, AA Yun, JH Curran, MA Borszuk, P Petrovick, L Novelline, RA TI Cerebral fractional anisotropy score in trauma patients: A new indicator of white matter injury after trauma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DIFFUSE AXONAL INJURY; STROKE AB OBJECTIVE. Previous studies evaluating quantitative cerebral white matter diffusion anisotropy indexes have shown alteration in patients after trauma. To date, no clinically applicable scale exists by which to gauge and test the relevance of these findings. We propose the cerebral fractional anisotropy score in trauma (C-FAST) as an index of white matter injury, and we correlate C-FAST with several predictor and outcome variables. MATERIALS AND METHODS. Fifteen patients were randomly selected from the trauma surgery service. Thirty control patients were randomly selected from the emergency department. All patients were subjected to MRI evaluation, including a diffusion-weighted sequence. Data extracted from the record of each subject included Glasgow Coma Scale, revised trauma score, Abbreviated Injury Scale, initial head CT results, patient disposition, length of hospital stay, and length of stay in intensive care unit. Region of interest measurements were made in fractional anisotropy maps in each of 12 white matter regions. Univariate statistics and a two-tailed t test were performed on the raw fractional anisotropy data. Data were then dichotomized using thresholds from univariate statistics. A C-FAST score was devised from the dichotomized data. Logistic regression analyses were performed among the C-FAST, outcome, and predictor data. RESULTS. Good correlation was noted between the C-FAST and death, hospital stay greater than 10 days, and intensive care unit stay greater than 5 days. Correlation with discharge to rehabilitation facility was good when adjusted for age and sex. Glasgow Coma Scale, revised trauma score, and Abbreviated Injury Scale show good correlation as predictors of a critical C-FAST. CONCLUSION. The C-FAST is a promising index derived from MRI diffusion fractional anisotropy measurements that shows successful correlation with outcome and predictor variables. A larger investigation is needed to verify the validity and stability of the correlations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Emergency Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma & Burn Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Ptak, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Emergency Radiol, 55 Fruit St,FND-210, Boston, MA 02114 USA. NR 9 TC 57 Z9 58 U1 0 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 NOV PY 2003 VL 181 IS 5 BP 1401 EP 1407 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 735RY UT WOS:000186129400056 PM 14573445 ER PT J AU Fagan, SP Awad, SS Rahwan, K Hira, K Aoki, N Itani, KMF Berger, DH AF Fagan, SP Awad, SS Rahwan, K Hira, K Aoki, N Itani, KMF Berger, DH TI Prognostic factors for the development of gangrenous cholecystitis SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAY 03-05, 2003 CL NASHVILLE, TENNESSEE SP Assoc VA Surg DE gangrenous cholecystitis; prognostic factors; multivariate logistic regression ID ACUTE ACALCULOUS CHOLECYSTITIS; LAPAROSCOPIC CHOLECYSTECTOMY; DIABETIC-PATIENTS; NATURAL-HISTORY; GALLBLADDER; RISK; PATIENT AB Background: The operative morbidity and mortality for patients with gangrenous cholecystitis (GC) remains high. Our objective was to identify preoperative prognostic factors for GC in order to distinguish this subset of patients with acute cholecystitis (AC). Methods: From 1/98 to 11/01 the medical records of patients who presented with the diagnosis of AC were reviewed. Univariate and multivariate analysis were performed on this retrospective data. Results: Of 113 patients with acute cholecystitis, 45 (39.8%) had histologically confirmed gangrenous cholecystitis. Nine variables were identified that were associated with GC by univariate analysis: age greater than or equal to51 years, African-American race, white blood cell count greater than or equal to15,000, diabetes, pericholecystic fluid, asparate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lipase. Two variables were identified by multivariate analysis: diabetes, and white blood cell count. Conclusions: Our data suggest that patients with a history of diabetes and white blood cell count >15,000 to be at an increased risk for having GC upon presentation and they should have urgent surgical intervention. (C) 2003 Excerpta Medica, Inc. All rights reserved. C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Houston Vet Affairs Med Ctr, Surg Serv Va 112, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Sch Hlth Informat, Houston, TX 77030 USA. RP Fagan, SP (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Houston Vet Affairs Med Ctr, Surg Serv Va 112, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 25 TC 37 Z9 40 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 NOV PY 2003 VL 186 IS 5 BP 481 EP 485 DI 10.1016/j.amjsung.2003.08.001 PG 5 WC Surgery SC Surgery GA 738UY UT WOS:000186307300013 PM 14599611 ER PT J AU Knauer, EM Ailawadi, G Yahanda, A Obermeyer, RJ Millie, MP Ojeda, H Mulholland, MW Colletti, L Sweeney, J AF Knauer, EM Ailawadi, G Yahanda, A Obermeyer, RJ Millie, MP Ojeda, H Mulholland, MW Colletti, L Sweeney, J TI 101 Laparoscopic splenectomies for the treatment of benign and malignant hematologic disorders SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAY 03-05, 2003 CL NASHVILLE, TENNESSEE SP Assoc VA Surg DE splenectomy; Laparoscopic; idiopathic thrombocytopenic purpura; splenomegaly ID DISEASES; EXPERIENCE; MANAGEMENT; SPLEENS AB Background: Laparoscopic splenectomy (LS) is the surgical approach of choice for patients with hematologic disorders requiring splenectomy. Patients with idiopathic thrombocytopenic purpura (ITP) have normal to slightly enlarged spleens and benefit the most from LS. Methods: We reviewed the perioperative outcomes in 101 patients who underwent LS between May 1996 and December 2002. Patients were divided into three groups-ITP, other benign, and malignant hematologic disorders-and compared. Results: The ITP patients (n = 48) had significantly smaller spleens and operative times compared with the other groups. Splenomegaly in the other benign (n = 23) and malignant hematologic disorders (n = 30) groups was responsible for higher open conversion rates and greater need for hand-assisted laparoscopic splenectomy (HALS). Conclusions: Laparoscopic splenectomy and HALS can be performed with good results for benign and malignant hematologic disorders. The benefits of HALS are similar to LS, so there should be a low threshold for HALS in patients with large spleens. (C) 2003 Excerpta Medica, Inc. All rights reserved. C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Houston VA Med Ctr, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA. Minimally Invas Surg, Houston, TX 77030 USA. RP Sweeney, J (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Houston VA Med Ctr, Houston, TX 77030 USA. NR 18 TC 32 Z9 42 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 NOV PY 2003 VL 186 IS 5 BP 500 EP 504 DI 10.1016/j.amjsurg.2003.07.026 PG 5 WC Surgery SC Surgery GA 738UY UT WOS:000186307300016 PM 14599614 ER PT J AU Logani, S Oliva, E Amin, MB Folpe, AL Cohen, C Young, RH AF Logani, S Oliva, E Amin, MB Folpe, AL Cohen, C Young, RH TI Immunoprofile of ovarian tumors with putative transitional cell (urothelial) differentiation using novel urothelial markers - Histogenetic and diagnostic implications SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Brenner tumor; transitional cell carcinoma of ovary; uroplakin III; thrombomodulin; immunohistochemistry ID BRENNER TUMORS; IMMUNOHISTOCHEMICAL ANALYSIS; BLADDER-CARCINOMA; MEMBRANE-PROTEINS; UROPLAKIN-III; EXPRESSION; CYTOKERATIN-20; THROMBOMODULIN; NEOPLASMS; ANTIBODIES AB Ovarian tumors containing cells with transitional cell morphology are recognized in the 1999 World Health Organization classification of ovarian tumors and include benign Brenner tumor, borderline and malignant Brenner tumor, and transitional cell carcinoma. Recent immunohistochemical investigations have reached conflicting conclusions regarding true urothelial differentiation in ovarian Brenner tumors. We evaluated a panel consisting of antibodies to uroplakin III (UROIII), thrombomodulin (THR), cytokeratin 7 (CK7), cytokeratin 20 (CK20), and Wilms' tumor protein (WT1) to study urothelial differentiation in ovarian transitional cell tumors. Additionally, we compared the immunohistochemical profile of transitional cell carcinoma of the ovary (TCC-O) with that of transitional cell carcinoma of the bladder (TCC-B), to ascertain if immunohistochemistry may aid in distinguishing primary from metastatic TCC-O. Seventeen benign Brenner tumors and 17 TCC-O were stained with antibodies to UROIII, THR, CK7, CK20, and WT1. Additionally, 6 Brenner tumors of borderline malignancy were stained with antibodies to UROIII, THR, CK7, and CK20. The immunohistochemical results were compared with those of 30 cases of noninvasive TCC-B (low malignant potential n = 14, low grade n = 16) and 36 cases of invasive TCC-B stained with a similar panel of antibodies as part of another study. Twenty-one nontransitional cell ovarian carcinomas (9 serous, 4 clear cell, 5 endometrioid, 2 mixed endometrioid/serous, and 1 mucinous) were used as controls. Most Brenner tumors showed positivity with UROIII (82%) and THR (76%), supporting true urothelial differentiation in these tumors. Although TCC-O has considerable morphologic overlap with TCC-B, they had only partial immunophenotypic overlap. TCC-O rarely expressed UROIII (6%) and THR (18%) and none expressed CK20. In contrast, nearly 40% of invasive TCC-B expressed UROIII, 61% expressed THR, and 50% expressed CK20. Nearly 82% of TCC-O expressed WT1, which was negative in all TCC-B. Our results may have diagnostic value in distinguishing TCC-O (CK20-, UROIII-/+, WT1+) and invasive TCC-B (CK20+, UROIII+/-, WT1-) metastatic to the ovary. They also indicate that the morphologic similarity between TCC-O and TCC-B does not indicate any histogenic similarity and, as others have noted, TCC-O is a variant morphology in the spectrum of surface epithelial carcinomas. C1 Emory Univ, Sch Med, Atlanta, GA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA USA. RP Logani, S (reprint author), Emory Univ Hosp, Dept Pathol, Suite H187,1364 Clifton Rd NE, Atlanta, GA 30322 USA. NR 39 TC 74 Z9 80 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2003 VL 27 IS 11 BP 1434 EP 1441 DI 10.1097/00000478-200311000-00005 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 737EE UT WOS:000186216200005 PM 14576476 ER PT J AU Yunis, EJ AF Yunis, EJ TI D. Bernard Amos: 1923-2003 - In memoriam SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Yunis, EJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. NR 2 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2003 VL 3 IS 11 BP 1448 EP 1449 DI 10.1046/j.1600-6135.2003.00271.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 737LA UT WOS:000186230800019 ER PT J AU Etzioni, DA Liu, JH O'Connell, JB Maggard, MA Ko, CY AF Etzioni, DA Liu, JH O'Connell, JB Maggard, MA Ko, CY TI Elderly patients in surgical workloads: A population-based analysis SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID TOTAL GASTRECTOMY; RISK-FACTORS; POSTOPERATIVE COMPLICATIONS; MEDICAL SPECIALTIES; GASTRIC-CANCER; COLON SURGERY; AGE; MORTALITY; OLDER; SURVIVAL AB Elderly (80+ year old) individuals are the fastest-growing segment of the U.S. population. The objective of this study was to use population-based data to examine trends in the number of elderly undergoing major general, vascular, and cardiothoracic surgical procedures. California inpatient data from 1990-2000 was used to identify patients undergoing six procedures: abdominal aortic aneurysm repair (AAA), coronary artery bypass graft (CABG), carotid endarterectomy (CEA), colon resections, lung resections, and pancreatic resections. Despite comprising only 2.7 per cent of the California population, elderly patients were a significant percentage (6-22%) of the caseloads for the six procedures examined. For all six procedures, the percentage of patients that were elderly increased during the study period. The age-specific incidence rates for elderly individuals increased significantly for three of these procedures (CABG, CEA, lung resection), remained unchanged for two (AAA, pancreas resection), and decreased for one (colon resection). Elderly patients are a large and growing part of surgical caseloads. In the near future, the number of elderly individuals in the California state and the U.S. populations will increase dramatically (41% and 35% between 2000 and 2020). To provide the best quality of care, surgeons should embrace research, training, and educational opportunities regarding the treatment of elderly patients. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Adm Med Ctr, Dept Gen Internal Med, Los Angeles, CA USA. RP Etzioni, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 911 Broxton Ave, Los Angeles, CA 90024 USA. NR 31 TC 56 Z9 57 U1 1 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD NOV PY 2003 VL 69 IS 11 BP 961 EP 965 PG 5 WC Surgery SC Surgery GA 741BZ UT WOS:000186440000009 PM 14627256 ER PT J AU Zingmond, D Maggard, M O'Connell, J Liu, J Etzioni, D Ko, C AF Zingmond, D Maggard, M O'Connell, J Liu, J Etzioni, D Ko, C TI What predicts serious complications in colorectal cancer resection? SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID OPERATIVE MORTALITY; COLON-CANCER; SURGERY; VOLUME; OUTCOMES; HOSPITALS AB Virtually all volume-outcome studies use mortality as their outcome measure, yet most general surgical procedures have low in-patient death rates. We examined whether hospital surgical volume impacts other colorectal cancer resection outcomes and complications. Colorectal cancer (CRC) resections from 1996 to 2000 were identified using the California hospital discharge database. Comorbidity was graded using a modified Charlson index. Hospital CRC resection volume was calculated. Serious medical complications were defined as life-threatening cardiac or respiratory events, renal failure, or shock. Serious surgical complications were defined as vascular events, need for reoperation, or bleeding. Multivariate logistic regression analyses were performed to estimate the impact of predictors on complications. We identified 56,621 resections. Median age was 70 to 74 years. Eighty-one per cent of patients were white. Most had localized (57%) versus distant (22%) disease. Serious medical (17.5%) and surgical (9.8%) complications were not infrequent. In multivariate analyses, greater annual CRC surgical volume predicted lower odds of serious complication, but patient characteristics (age, comorbidity, and acuity of surgery) were more important. Although patients receiving CRC resection at lower-volume hospitals have greater odds of complication than patients treated at higher-volume institutions, patient factors remain the most important determinants of complication. C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. W Los Angeles VA, Los Angeles, CA USA. RP Ko, C (reprint author), 10833 LeConte Ave,72-215 CHS, Los Angeles, CA 90095 USA. NR 16 TC 19 Z9 19 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD NOV PY 2003 VL 69 IS 11 BP 969 EP 974 PG 6 WC Surgery SC Surgery GA 741BZ UT WOS:000186440000011 PM 14627258 ER PT J AU Sedeek, KA Takeuchi, M Suchodolski, K Vargas, SO Shimaoka, M Schnitzer, JJ Kacmarek, RM AF Sedeek, KA Takeuchi, M Suchodolski, K Vargas, SO Shimaoka, M Schnitzer, JJ Kacmarek, RM TI Open-lung protective ventilation with pressure control ventilation, high-frequency oscillation, and intratracheal pulmonary ventilation results in similar gas exchange, hemodynamics, and lung mechanics SO ANESTHESIOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; TIDAL VOLUME; RECRUITMENT; INJURY; INFLATION; ADULTS; TRIAL; EDEMA; INSUFFLATION AB Background. Pressure control ventilation (PCV), high-frequency oscillation (HFO), and intratracheal pulmonary ventilation (ITPV) may all be used to provide lung protective ventilation in acute respiratory distress syndrome, but the specific approach that is optimal remains controversial. Methods: Saline lavage was used to produce acute respiratory distress syndrome in 21 sheep randomly assigned to receive PCV, HFO, or ITPV as follows: positive end-expiratory pressure (PCV and ITPV) and mean airway pressure (HFO) were set in a pressure-decreasing manner after lung recruitment that achieved a ratio of Pao(2)/FIO2 > 400 mmHg. Respiratory rates were 30 breaths/min, 120 breaths/min, and 8 Hz, respectively, for PCV, ITPV, and HFO. Eucapnia was targeted with peak carinal pressure of no more than 35 cm H2O. Animals were then ventilated for 4 h. Results: There were no differences among groups in gas exchange, lung mechanics, or hemodynamics. Tidal volume (PCV, 8.9 +/- 2.1 ml/kg; ITPV, 2.7 +/- 0.8 ml/kg; HFO, approximately 2.0 ml/kg) and peak carinal pressure (PCV, 30.6 +/- 2.6 cm H2O; ITPV, 22.3 +/- 4.8 CM H2O; HFO, approximately 24.3 cm H2O) were higher in PCV. Pilot histologic data showed greater interstitial hemorrhage and alveolar septal expansion in PCV than in HFO or ITPV. Conclusion: These data indicate that HFO, ITPV, and PCV when applied with an open-lung protective ventilatory strategy results in the same gas exchange, lung mechanics, and hemodynamic response, but pilot data indicate that lung injury may be greater with PCV. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Surg, Ellison 401, Boston, MA 02114 USA. NR 31 TC 24 Z9 27 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 NOV PY 2003 VL 99 IS 5 BP 1102 EP 1111 DI 10.1097/00000542-200311000-00016 PG 10 WC Anesthesiology SC Anesthesiology GA 737NZ UT WOS:000186239800015 PM 14576546 ER PT J AU Dieter, RS Murtaugh, T Black, J Russell, DC AF Dieter, RS Murtaugh, T Black, J Russell, DC TI Coronary arteriomegaly in a patient with Ehlers-Danlos syndrome and multiple aneurysms - A case report SO ANGIOLOGY LA English DT Article ID ABDOMINAL AORTIC-ANEURYSMS; LOCALIZATION; LOCUS AB The authors report a case of coronary arteriomegaly in a patient with Ehlers-Danlos syndrome and multiple aneurysms who presented with myocardial infarction. Coronary arteriography revealed distal "pruning" of vessels without occlusive disease. Fibroblast cultures excluded Ehlers-Danlos syndrome types IV and VII. Literature review suggests this may represent a previously unidentified vascular syndrome. C1 William S Middleton Mem Vet Adm Med Ctr, Cardiol Sect 111CA, Madison, WI 53705 USA. Univ Wisconsin, Madison, WI USA. RP Russell, DC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Cardiol Sect 111CA, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NHLBI NIH HHS [T32 HL07936] NR 10 TC 6 Z9 6 U1 0 U2 1 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 0003-3197 J9 ANGIOLOGY JI Angiology PD NOV-DEC PY 2003 VL 54 IS 6 BP 733 EP 736 DI 10.1177/000331970305400616 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 746LP UT WOS:000186748100016 PM 14666965 ER PT J AU Kim, S Camargo, CA AF Kim, S Camargo, CA TI Sex-race differences in the relationship between obesity and asthma: The Behavioral Risk Factor Surveillance System, 2000 SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE asthma; obesity; sex; race/ethnicity ID BODY-MASS INDEX; SELF-REPORTED WEIGHT; AIRWAY HYPERRESPONSIVENESS; NUTRITION EXAMINATION; NATIONAL-HEALTH; UNITED-STATES; PLASMA LEPTIN; US ADULTS; PREVALENCE; ASSOCIATION AB PURPOSE: Although prospective data are limited, recent cross-sectional studies support obesity as a cause of asthma. They also suggest that the association is present only among women. Our analysis examines possible sex-race differences in the relationship between obesity and asthma. METHODS: We examined data from the 2000 Behavioral Risk Factor Surveillance System. To minimize diagnostic bias, the sample was limited to adults aged 18 to 34 years. All cases had doctor-diagnosis of asthma and ongoing symptoms. Multiple logistic regression was used to examine risk factors for current asthma vs. never having asthma. RESULTS: Obesity and asthma were more strongly related among women than men (test for interaction, p < 0.01). Across increasing categories of body mass index (BMI), we observed a dose-response relationship among women (odds ratios: 0.9, 1.0 [reference], 1.0, 1.3, 1.5, 1.8, and 3.2) but only a non-significant increased risk in severely obese men (odd ratio: 2.0). In subgroup analyses, however, the obesity-asthma association was present in four of six sex-race/ethnicity subgroups, including black and Hispanic men. CONCLUSIONS: Although the obesity-asthma association is stronger among women than men, our analysis demonstrates a strong positive association among men from minority groups. These race-specific results may help explain some of the "inconsistencies" in prior studies. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, 55 Fruit St,Clin Bldg 397, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-63841, HL-04095] NR 46 TC 52 Z9 56 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2003 VL 13 IS 10 BP 666 EP 673 DI 10.1016/S1047-2797(03)00054-1 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 741PX UT WOS:000186467400002 PM 14599730 ER PT J AU Roberts, PS Ramesh, V Dabora, S Kwiatkowski, DJ AF Roberts, PS Ramesh, V Dabora, S Kwiatkowski, DJ TI A 34 bp deletion within TSC2 is a rare polymorphism, not a pathogenic mutation SO ANNALS OF HUMAN GENETICS LA English DT Article ID TUBEROUS-SCLEROSIS PATIENTS; GERMLINE MUTATIONS; UNRELATED PATIENTS; GENE; IDENTIFICATION; HAMARTIN; COMPLEX; MTOR; 9Q34 AB Tuberous sclerosis (TSC) is an autosomal dominant hamartoma syndrome due to mutations in either TSC1 or TSC2. Previous reports have identified a mutation consisting of a 34 bp deletion affecting portions of exon 38 and the adjacent intron 38 of TSC2. We found this genetic variation in 4 of 800 TSC patients screened for mutations in TSC1 and TSC2. In every case, the variant was present in one unaffected parent of the sporadically affected TSC child. By RT-PCR analysis of RNA samples from two additional families with this genetic variant, we demonstrate that the allele with the deletion generates about 50% normal RNA transcript, and 50% RNA transcript including intron 38. In addition, there is no correlation between the extent of splicing and clinical status of family members. We also excluded the possibility of mosaicism in the parents with this variant. We conclude that this deletion is a rare polymorphism that does not cause TSC, but may be a modifier of the TSC phenotype. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Hematol Div, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, 221 Longwood Ave,LMRC 302, Boston, MA 02115 USA. FU PHS HHS [24279, 31535] NR 19 TC 7 Z9 7 U1 0 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD NOV PY 2003 VL 67 BP 495 EP 503 DI 10.1046/j.1529-8817.2003.00059.x PN 6 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 755ZU UT WOS:000187442000002 PM 14641237 ER PT J AU Mahmud, MR Khan, AM Nadol, JB AF Mahmud, MR Khan, AM Nadol, JB TI Histopathology of the inner ear in unoperated acoustic neuroma SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE acoustic neuroma; hearing loss; histopathology; vestibular schwannoma ID AUDITORY-CANAL PRESSURE; VESTIBULAR SCHWANNOMAS; TEMPORAL BONE; COCHLEAR NERVE; HEARING-LOSS; PATHOLOGY; NEURINOMA; PROTEINS; PERILYMPH; FLUID AB Although hearing loss is the most common presenting symptom in patients with acoustic neuroma, the pathophysiology of hearing loss associated with acoustic neuroma is unknown. Although primary dysfunction of the auditory nerve is intuitively logical, available histopathologic and clinical data suggest that although neural degeneration is common, it alone does not adequately account for hearing loss in many cases. The purpose of this study was to evaluate I I cases of unoperated unilateral acoustic neuromas. Temporal bones were identified by means of a search mechanism provided by the National Temporal Bone, Hearing, and Balance Pathology Resource Registry and were prepared for light microscopy by standard techniques. Quantification of spiral ganglion cells, hair cells. stria vascularis, and spiral ligament was accomplished for each specimen. In addition, the maximum diameter and volume of each tumor were calculated from histopathologic sections. Increasing tumor size did predict a reduced spiral ganglion count. However, although there was a tendency for decreasing spiral ganglion cell count and for increasing tumor size to predict a higher pure tone average and lower speech discrimination score, these correlations did not reach statistical significance. In tumor ears in which the speech discrimination score was 50% or less, there was always significant degeneration of other structures of the inner ear in addition to neurons, including hair cells, the stria vascularis, and the spiral ligament. Endolymphatic hydrops and eosinophilic precipitate in the perilymphatic spaces were found in 2 of 3 such cases. It is concluded that acoustic neuromas appear to cause hearing loss. not only by causing degeneration of the auditory nerve, but also by inducing degenerative changes in the inner ear. It is hypothesized that the proteinaceous material seen histologically may represent the products of up-regulated genes in acoustic neuroma. some of which may interfere with normal cochlear function. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Univ Kebangsaan Malaysia, Dept Otolaryngol, Kuala Lumpur, Malaysia. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 22 TC 26 Z9 26 U1 0 U2 5 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 2003 VL 112 IS 11 BP 979 EP 986 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 743CC UT WOS:000186554000011 PM 14653368 ER PT J AU Esnaola, NF Mirza, N Lauwers, GY Ikai, I Regimbeau, JM Belghiti, J Yamaoka, Y Curley, SA Ellis, LM Nagorney, DM Vauthey, JN AF Esnaola, NF Mirza, N Lauwers, GY Ikai, I Regimbeau, JM Belghiti, J Yamaoka, Y Curley, SA Ellis, LM Nagorney, DM Vauthey, JN TI Comparison of clinicopathologic characteristics and outcomes after resection in patients with hepatocellular carcinoma treated in the United States, France, and Japan SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 5th World Congress of the International-Hepato-Pancreato-Biliary-Association CY 2002 CL TOKYO, JAPAN SP Int Hepato Pancreato Biliary Assoc ID HEPATITIS-B; CLINICAL-SIGNIFICANCE; ARTERIAL PORTOGRAPHY; NONCIRRHOTIC LIVER; EXPERIENCE; RECURRENCE; PROGNOSIS; INVASION; SYSTEM; CT AB Objective: To compare the clinicopathologic characteristics and outcomes after resection of patients with hepatocellular carcinoma (HCC) treated in the United States, France, and Japan. Summary Background Data: Some epidemiologic data suggests that HCC in different regions of the world may represent different forms of the disease. Methods: We compared the patient and tumor characteristics, underlying liver damage, and surgical outcomes of 586 patients who underwent resection of HCC from a multi-institutional database. Results: A total of 169 patients were treated in the United States, 197 in France, and 230 in Japan. The median tumor size for patients treated in the United States was 8 cm, compared with 6 cm and 3.5 cm in France and Japan, respectively (P < 0.001); 20%, 38%, and 74% of patients in the United States, France, and Japan, respectively, had positive hepatitis C serology (P < 0.001). In addition, 65% of patients in Japan had severe fibrosis/cirrhosis in the adjacent liver compared with 52% and 23% of patients in France and the United States, respectively (P < 0.001). There was no association between site of treatment and 30-day (P = O.A) or 1-year mortality (P = 0.3). The 5-year survival of patients treated in United States, France, and Japan was not statistically different (31% vs. 31% vs. 41%, respectively; P = 0.3). Conclusions: Although the etiology of HCC and clinicopathologic characteristics of patients treated at western and eastern centers vary widely, postresection 5-year survival is similar when controlling for these factors. Future studies should account for histopathologic differences using uniform criteria to allow better comparison of results. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Kyoto Univ, Dept Surg, Grad Sch Med, Kyoto, Japan. Hop Beaujon, Dept Surg, Paris, France. Mayo Clin, Dept Surg, Rochester, MN USA. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, 1515 Holcombe Blvd,Box 444, Houston, TX 77030 USA. FU PHS HHS [T32] NR 42 TC 59 Z9 62 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD NOV PY 2003 VL 238 IS 5 BP 711 EP 719 DI 10.1097/01.sla.0000094436.34556.ac PG 9 WC Surgery SC Surgery GA 738VJ UT WOS:000186308300012 PM 14578734 ER PT J AU Etzioni, DA Liu, JH Maggard, MA O'Connell, JB Ko, CY AF Etzioni, DA Liu, JH Maggard, MA O'Connell, JB Ko, CY TI Workload projections for surgical oncology: Will we need more surgeons? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Society-of-Surgical-Oncology CY MAR 07, 2003 CL LOS ANGELES, CALIFORNIA SP Soc Surg Oncol DE workload; workforce; aging; projection; surgery ID FECAL OCCULT-BLOOD; COLORECTAL-CANCER; GENERAL-SURGERY; SCREENING PRACTICES; UNITED-STATES; TRENDS; CALIFORNIA; PROGRESS; IMPACT AB Background: Over the next two decades, the US population will experience dramatic growth in the number and relative proportion of older individuals. The aim of this study was to quantify the effect of these changes on the demand for oncological procedures. Methods: The 2000 Nationwide Inpatient Sample and the 1996 National Survey of Ambulatory Surgery were used to compute age-specific incidence rates for oncological procedures of the breast, colon, rectum, stomach, pancreas, and esophagus. Procedure rates were combined with census projections for 2010 and 2020 to estimate the future utilization of each procedure. Results: By 2020, the number of patients undergoing oncological procedures is projected to increase by 24% to 51%. The bulk of growth in procedures is derived from outpatient procedures, but significant growth will also be seen in inpatient procedures. Conclusions: The aging of the population will generate an enormous growth in demand for oncological procedures. If a shortage of surgeons performing these procedures does occur, the result will inevitably be decreased access to care. To prevent this from happening, the ability of surgeons to cope with an increased burden of work needs to be critically evaluated and improved. C1 Univ Calif Berkeley, Dept Surg, David Geffen Sch Med, Santa Monica, CA 90403 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Etzioni, DA (reprint author), Univ Calif Berkeley, Dept Surg, David Geffen Sch Med, 1015 9th St,Apt 106, Santa Monica, CA 90403 USA. NR 20 TC 36 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD NOV PY 2003 VL 10 IS 9 BP 1112 EP 1117 DI 10.1245/ASO.2003.03.034 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 740NU UT WOS:000186409100021 PM 14597452 ER PT J AU Rumsfeld, JS AF Rumsfeld, JS TI In the world of heart valves size matters - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80220 USA. RP Rumsfeld, JS (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, 1055 Clermont St 111B, Denver, CO 80220 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2003 VL 76 IS 5 BP 1604 EP 1604 DI 10.1016/S0003-4975(03)01033-6 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 739QU UT WOS:000186358600050 ER PT J AU Shadmehr, MB Gaissert, HA Wain, JC Moncure, AC Grillo, HC Borges, LF Mathisen, DJ AF Shadmehr, MB Gaissert, HA Wain, JC Moncure, AC Grillo, HC Borges, LF Mathisen, DJ TI The surgical approach to "dumbbell tumors" of the mediastinum SO ANNALS OF THORACIC SURGERY LA English DT Article ID NEUROGENIC TUMORS; THORACOTOMY; MANAGEMENT; PARAPLEGIA; DIAGNOSIS; EXCISION; REMOVAL AB Background. Successful management of posterior mediastinal dumbbell tumors depends on complete resection with adequate exposure. Correct preoperative assessment of neuroforaminal extension is important to avoid spinal cord injury. The surgical approach remains controversial. Methods. We report a retrospective analysis of posterior mediastinal dumbbell tumors over a 28-year period. All patients underwent one or more radiographic examinations available at the time of presentation and underwent a single-stage one-incision combined thoracic and neurosurgical procedure. Results. Among 16 patients aged 5 to 76 years, neuroforaminal involvement was identified before operation in 14 (87.5%) and during the procedure in 2 patients (12.5%). Computed tomography scan missed neuroforaminal involvement in 3 patients. Magnetic resonance imaging in 9 patients correctly identified neuroforaminal extension of the tumor but before MRI myelography missed this extension in 3 patients. All patients underwent thoracotomy and posterior laminectomy was required in 10 of them. In 6 patients (38%) without laminectomy, resection required widening of the neural foramen in 3 whereas tumor was removed in 3 others through an already widened foramen. Spinal stabilization was required in 2 patients. There were 14 benign and 2 malignant lesions. Complete resection was performed in all patients without spinal cord injury or other major complication. No recurrences have been observed in a follow-up period from 2 months to 28 years (mean, 7.5 years). Conclusions. Posterior mediastinal tumors should be evaluated for neuroforaminal involvement. A single-stage combined thoracic and neurosurgical approach is safe and leads to good long-term results. Laminectomy may be avoided in some patients. (C) 2003 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. OI shadmehr, mohammad behgam/0000-0002-3303-6750 NR 25 TC 21 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2003 VL 76 IS 5 BP 1650 EP 1654 DI 10.1016/S0003-4975(03)00882-8 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 739QU UT WOS:000186358600060 PM 14602303 ER PT J AU Tremblay, CL Poulin, DL Hicks, JL Selliah, S Chamberland, A Giguel, F Kollmann, CS Chou, TC Dong, HJ Hirsch, MS AF Tremblay, CL Poulin, DL Hicks, JL Selliah, S Chamberland, A Giguel, F Kollmann, CS Chou, TC Dong, HJ Hirsch, MS TI Favorable interactions between enfuvirtide and 1-beta-D-2,6-diaminopurine dioxolane in vitro SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; FUSION INHIBITOR; HIV-1; REPLICATION; MECHANISM; STAVUDINE; INFECTION; T-20 AB We evaluated the in vitro anti-human immunodeficiency virus type 1 (HIV-1) interactions between 1-beta-D-2,6-diaminopurine dioxolane (DAPD) and enfuvirtide (T-20) against clinical isolates sensitive and resistant to reverse transcriptase and protease inhibitors. Interactions between T-20 and DAPD were synergistic to nearly additive, with combination index values ranging from 0.53 to 1.06 at 95% inhibitory concentrations. These studies suggest that a combination of T-20 and DAPD might be useful in the, treatment of antiretroviral drug-experienced patients. C1 Univ Montreal, Ctr Hosp, Montreal, PQ H2W 1T8, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Hirsch, MS (reprint author), Univ Montreal, Ctr Hosp, Pavillon Jeanne Mance,Bur 7-355, Montreal, PQ H2W 1T8, Canada. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NIAID NIH HHS [AI-49414, R01 AI049414] NR 15 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2003 VL 47 IS 11 BP 3644 EP 3646 DI 10.1128/AAC.47.11.3644-3646.2003 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 738WT UT WOS:000186311400047 PM 14576137 ER PT J AU Connor, JA Smaldone, AM Bratts, T Stone, PW AF Connor, JA Smaldone, AM Bratts, T Stone, PW TI HIPAA in 2003 and its meaning for nurse researchers SO APPLIED NURSING RESEARCH LA English DT Editorial Material C1 Childrens Hosp Boston, Harvard Pediat Hlth Serv Res Fellowship Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr Training Grant Diabet & Metab, Boston, MA USA. Columbia Univ, Sch Nursing, New York, NY USA. RP Connor, JA (reprint author), Childrens Hosp Boston, Harvard Pediat Hlth Serv Res Fellowship Program, 300 Longwood Ave,LO-244, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD NOV PY 2003 VL 16 IS 4 BP 291 EP 293 DI 10.1053/S089701897(03)00081-8 PG 3 WC Nursing SC Nursing GA 746LL UT WOS:000186747800010 PM 14608564 ER PT J AU Cheng, XF Mao, JM Bush, R Kopans, DB Moore, RH Chorlton, M AF Cheng, XF Mao, JM Bush, R Kopans, DB Moore, RH Chorlton, M TI Breast cancer detection by mapping hemoglobin concentration and oxygen saturation SO APPLIED OPTICS LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; TUMOR XENOGRAFTS; TISSUE; REFLECTANCE AB Near-infrared (NIR) spectroscopic imaging technology provides a new modality for measuring changes in total hemoglobin concentration (HbT) and blood oxygen saturation (SO2) in human tissue. The technology can be used to detect breast cancer because cancers may cause greater vascularization and greater oxygen consumption than in normal tissue. Based on the NIR technology, ViOptix, Inc., has developed an optical device that provides two-dimensional mapping of HbT and SO2 in human tissue. As an adjunctive tool to mammography, the device was preliminarily tested in a clinical trial with 50 mammogram-positive patients at the Massachusetts General Hospital. The results of the clinical trial demonstrate that the device can reach as much as 92% diagnostic sensitivity and 67% specificity in detecting ductal carcinoma. These results may indicate that the NIR technology can potentially be used as an adjunct to mammography for breast cancer detection to reduce the number of biopsies performed. (C) 2003 Optical Society of America. C1 ViOptix Inc, Fremont, CA 94538 USA. Massachusetts Gen Hosp, Div Breast Imaging, Boston, MA 02114 USA. RP Cheng, XF (reprint author), ViOptix Inc, 44061 B Old Warm Spring Blvd, Fremont, CA 94538 USA. EM maoj@vioptix.com NR 23 TC 54 Z9 57 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD NOV 1 PY 2003 VL 42 IS 31 BP 6412 EP 6421 DI 10.1364/AO.42.006412 PG 10 WC Optics SC Optics GA 739TN UT WOS:000186362700022 PM 14649285 ER PT J AU Tohen, M Vieta, E Calabrese, J Ketter, TA Sachs, G Bowden, C Mitchell, PB Centorrino, F Risser, R Baker, RW Evans, AR Beymer, K Dube, S Tollefson, GD Breier, A AF Tohen, M Vieta, E Calabrese, J Ketter, TA Sachs, G Bowden, C Mitchell, PB Centorrino, F Risser, R Baker, RW Evans, AR Beymer, K Dube, S Tollefson, GD Breier, A TI Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Collegium International Neuro-Psychopharmacologium Regional Meeting (CINP) CY JUN 23, 2002 CL MONTREAL, CANADA ID DOUBLE-BLIND; ACUTE MANIA; DISORDER; PLACEBO; LAMOTRIGINE; SCALE; SCHIZOPHRENIA; DIVALPROEX; MANAGEMENT; ILLNESS AB Background: Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers, relatively few controlled studies have examined treatment strategies for bipolar depression. Objective: To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Design: Double-blind, 8-week, randomized controlled trial. Setting: Eighty-four sites (inpatient and outpatient) in 13 countries. Patients: A total of 833 randomized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 20. Intervention: Patients were randomly assigned to receive placebo (n=377); olanzapine, 5 to 20 mg/d (n=370); or olanzapine-fluoxetine combination, 6 and 25, 6 and 50, or 12 and 50 mg/d (n=86). Main Outcome Measure: Changes in MADRS total scores using mixed-effects model repeated-measures analyses. Results: During all 8 study weeks, the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs; the placebo group (P<.001 for all). The olanzapine-fluoxetine group also showed statistically greater improvement than the olanzapine group at weeks 4 through 8. At week 8, MADRS total scores were lower than at baseline by 11.9, 15.0, and 18.5 points in the placebo, olanzapine, and olanzapine-fluoxetine groups, respectively. Remission criteria were met by 24.5% (87/355) of the placebo group, 32.8% (115/ 351) of the olanzapine group, and 48.8% (40/82) of the olanzapine-fluoxetine group. Treatment-emergent mania (Young Mania Rating Scale score <15 at baseline and less than or equal to15 subsequently) did not differ among groups (placebo, 6.7% [23/345]; olanzapine, 5.7% [19/335]; and olanzapine-fluoxetine, 6.4% [5/78]). Adverse events for olanzapine-nuoxetine therapy were similar to those for olanzapine therapy but also included higher rates of nausea and diarrhea. Intervention: Patients were randomly assigned to receive placebo (n=377); olanzapine, 5 to 20 mg/d (n=370); or olanzapine-fluoxetine combination, 6 and 25, 6 and 50, or 12 and 50 mg/d (n=86). Main Outcome Measure: Changes in MADRS total scores using mixed-effects model repeated-measures analyses. Conclusions: Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms. C1 Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Psychiat, Cleveland, OH 44106 USA. Hosp Clin Barcelona, Bipolar Disorders Program, Barcelona, Spain. Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. RP Tohen, M (reprint author), Lilly Res Labs, Indianapolis, IN 46285 USA. RI Vieta, Eduard/I-6330-2013; OI Vieta, Eduard/0000-0002-0548-0053; Mitchell, Philip/0000-0002-7954-5235 NR 38 TC 567 Z9 584 U1 4 U2 38 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2003 VL 60 IS 11 BP 1079 EP 1088 DI 10.1001/archpsyc.60.11.1079 PG 10 WC Psychiatry SC Psychiatry GA 744DH UT WOS:000186612300003 PM 14609883 ER PT J AU Schellenberg, GD AF Schellenberg, GD TI Alzheimer Disease genes - Presenilin 2 mutation number 9 and still counting SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID MISSENSE MUTATIONS C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Schellenberg, GD (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,Mail Code 182B,Box 358280, Seattle, WA 98108 USA. NR 9 TC 4 Z9 4 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 NOV PY 2003 VL 60 IS 11 BP 1521 EP 1522 DI 10.1001/archneur.60.11.1521 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 744DC UT WOS:000186611800002 PM 14623722 ER PT J AU Boninger, ML Dicianno, BE Cooper, RA Towers, JD Koontz, AM Souza, AL AF Boninger, ML Dicianno, BE Cooper, RA Towers, JD Koontz, AM Souza, AL TI Shoulder magnetic resonance imaging abnormalities, wheelchair propulsion, and gender SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE biomechanics; gender; magnetic resonance imaging; paraplegia; rehabilitation; shoulder; wheelchairs ID BEARING UPPER EXTREMITY; LONG-TERM PARAPLEGIA; IMPINGEMENT SYNDROME; PUSHRIM FORCES; 2 SPEEDS; WEIGHT; PAIN; BIOMECHANICS; INDIVIDUALS; INJURIES AB Objective: To investigate the relationship between pushrim forces and the progression of shoulder injuries in manual wheelchair users. Design: Longitudinal case series. Setting: Biomechanics laboratory and magnetic resonance imaging (MRI) facility at a Veterans Health Administration medical center and university hospital, respectively. Participants: Fourteen individuals with spinal cord injury (8 men. 6 women) who used manual wheelchairs. Intervention: Subjects propelled their own wheelchairs on a dynamometer at 0.9 and 1.8m/s. Bilateral biomechanical data were obtained by using force and moment sensing pushrims at time 1. Bilateral shoulder MR images were also completed on 2 occasions. at time I and, approximately 2 years later, at time 2. Main Outcome Measures: The peak pushrim forces in a pushrim coordinate system were calculated, weight normalized and averaged over 5 strokes (presented as % body weight). MRI abnormalities were graded by using a summated scale Differences between scores between times I and 2 were calculated. Results: Subjects were divided into 2 groups based on change in MRI score. Seven subjects were in the group with worsening scores (MRI+: mean, 8.14 points, range, 5-16), and 7 were in the group with improving or unchanging scores (MRI-: mean. -1.00 point; range, -5 to 1). There was no significant difference between groups with respect to age, body mass index. or years from injury. There were significantly more women in the MRI+ group (6 women, I man) than in the MRI- group (7 men) (P=.001). The MRI+ group used significantly greater weight-normalized radial force, or force directed toward the axle at time 1, to propel their wheelchairs at each speed (P<.01): MRI+ at 0.9m/s (mean radial force standard deviation, 5.2%+/-1.0%) and MRI- at 0.9m/s (mean radial force, 3.2%+/-1.7%) (P=.028); and MRI+ at 1.8m/s (mean radial force, 6.6%+/-1.2%) (P=.023) and MRI- at 1.8m/s (mean radial force, 4.1%+/-2.2%). In a separate analysis, women were found to propel with a significantly higher radial force. A logistic regression found a significant relationship between radial force at time I and increased risk of progression of MRI findings over time. Conclusion: Individuals who propel with a greater percentage of force directed toward the axle were at increased risk of progression of MRI findings over time. Most people in this group were women. Clinicians should instruct wheelchair users in effective propulsion techniques and should pay particular attention to women who use wheelchairs. Reducing forces during wheelchair propulsion may minimize the likelihood of developing shoulder injuries. C1 VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Human Engn Res Labs, Dept Phys Med & Rehabil, Sch Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Sch Hlth & Rehabil Sci, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Radiol, Med Ctr, Pittsburgh, PA 15260 USA. RP Boninger, ML (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, 5180 Highland Dr,151R-1, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X; Dicianno, Brad/0000-0003-0738-0192 FU NICHD NIH HHS [1 P01 HD33989] NR 33 TC 41 Z9 45 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2003 VL 84 IS 11 BP 1615 EP 1620 DI 10.1053/S0003-9993(03)00282-X PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 741PR UT WOS:000186466900007 PM 14639560 ER PT J AU Petchkrua, W Burns, SA Stiens, SA James, JJ Little, JW AF Petchkrua, W Burns, SA Stiens, SA James, JJ Little, JW TI Prevalence of vitamin B-12 deficiency in spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE rehabilitation; spinal cord injuries; vitamin B12 deficiency ID SUBTLE COBALAMIN DEFICIENCY; METHYLMALONIC ACID; DIAGNOSIS; ABNORMALITIES; OUTPATIENTS; INDIVIDUALS; POPULATION; ANEMIA; FOLATE; RISK AB Objective: To assess the prevalence of vitamin B-12 deficiency in persons with spinal cord injury (SCI) or disease (SCD). Design: Cross-sectional study with prospective blood collection and retrospective medical record review. Setting: Regional Veterans Affairs SCI service. Participants: One hundred six adult men with chronic SCI or SCD and without other acute medical or surgical complications; most had SCI or SCD due to trauma or cervical spinal stenosis. Interventions: Not applicable. Main Outcome Measures: Fasting blood samples were obtained at annual evaluation for serum B12, folic acid, methylmalonic acid (MMA), and homocysteine. Serum levels were analyzed graphically and associated with patient variables by using statistical tests. Results: The vitamin B-12 level was subnormal in 5.7% of subjects: of those. all had supranormal MMA levels, all were age 40 to 59. most had complete SCI, and 67% had symptoms suggestive of B-12 deficiency. Low-normal B-12 levels were associated with a high prevalence of supranormal MMA. Subjects with either subnormal B-12 or low normal B-12 with supranormal MMA. both suggestive of vitamin 13, deficiency, comprised 13.3% of the total group of subjects. Conclusion: Vitamin B-12 deficiency is most common in middle-aged SCI or SCD persons with complete or near-complete spinal cord involvement (ie, American Spinal Injury Association class A-C injuries). Treatment with either parenteral or oral B-12 replacement may optimize health and prevent irreversible neuropsychiatric complications in those with subnormal and low-normal B-12 levels. C1 VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv S128, Dept Vet Affairs, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Little, JW (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv S128, Dept Vet Affairs, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 33 TC 11 Z9 12 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2003 VL 84 IS 11 BP 1675 EP 1679 DI 10.1053/S0003-9993(03)00318-6 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 741PR UT WOS:000186466900016 PM 14639569 ER PT J AU Warshaw, AL AF Warshaw, AL TI Department of Surgery, Massachusetts General Hospital, Boston SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD NOV PY 2003 VL 138 IS 11 BP 1173 EP 1174 DI 10.1001/archsurg.138.11.1173 PG 2 WC Surgery SC Surgery GA 742BV UT WOS:000186496100001 PM 14609863 ER PT J AU Waters, GS Caplan, D AF Waters, GS Caplan, D TI The reliability and stability of verbal working memory measures SO BEHAVIOR RESEARCH METHODS INSTRUMENTS & COMPUTERS LA English DT Article ID SHORT-TERM-MEMORY; ADULT AGE-DIFFERENCES; INDIVIDUAL-DIFFERENCES; FLUID INTELLIGENCE; ALZHEIMERS-DISEASE; LIFE-SPAN; CAPACITY; COMPREHENSION; PERFORMANCE; TASK AB The psychometric properties of several commonly used verbal working memory measures were assessed. One hundred thirty-nine individuals in five age groups (18-30, 50-59, 60-69, 70-79, and 80+ years) were tested twice (Time I and Time II) on seven working memory span measures (alphabet span, backward digit span, missing digit span, subtract 2 span, running item span, and sentence span for syntactically simple and complex sentences), with an interval of approximately 6 weeks between testing. There were significant effects of age on all but two of the tasks. All the measures had adequate internal consistency. Correlations between performances at Time I andTime II were significant for all the tasks, other than the missing digit span task. The magnitude of the correlations was similar across the age groups and ranged from .52 to .81. Classification of subjects into discrete memory span groups on the basis of a single measure was highly inconsistent across testing sessions and tasks. Classification into upper and lower quartiles was more stable than using a cutoff score for group membership or than classification into high-, medium-, and low-span groups. Correlational analyses showed that there was a moderate relationship between performances on many of the span tasks. Confirmatory factor analysis suggested that six of the seven tasks reflected a common factor. Both test-retest reliability and stability of classification improved when a composite measure reflecting performance on several tasks was used. C1 Boston Univ, Boston, MA 02116 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Waters, GS (reprint author), Boston Univ, 635 Commonwealth Ave, Boston, MA 02116 USA. EM gwaters@bu.edu FU NIA NIH HHS [AG00966] NR 52 TC 93 Z9 93 U1 2 U2 6 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0743-3808 J9 BEHAV RES METH INS C JI Behav. Res. Methods Instr. Comput. PD NOV PY 2003 VL 35 IS 4 BP 550 EP 564 DI 10.3758/BF03195534 PG 15 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA 761NZ UT WOS:000187916000008 PM 14748499 ER PT J AU Otto, MW Hinton, D Korbly, NB Chea, A Ba, P Gershuny, BS Pollack, MH AF Otto, MW Hinton, D Korbly, NB Chea, A Ba, P Gershuny, BS Pollack, MH TI Treatment of pharmacotherapy-refractory posttraumatic stress disorder among Cambodian refugees: a pilot study of combination treatment with cognitive-behavior therapy vs sertraline alone SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE posttraumatic stress disorder; refugee; Cambodian; cognitive-behavioral therapy; cross-cultural; treatment-resistance; antidepressants ID EXPOSURE; VICTIMS AB Cambodian refugees with posttraumatic stress disorder (PTSD) represent a cohort in severe need of treatment, but little information is available to guide treatment choices. We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy (CBT) for treating PTSD. Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22-26 years during the Pol Pot period (1975-1979). These patients were randomly assigned to either sertraline alone or combined treatment. We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms. Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD, and that a program of CBT emphasizing information, exposure, and cognitive-restructuring can be successfully modified for Khmer-speaking refugees. (C) 2003 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. SE Asian Community Clin, N Suffolk Mental Hlth Assoc, Revere, MA 02151 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, WACC 812,15 Pkman St, Boston, MA 02114 USA. NR 14 TC 97 Z9 99 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD NOV PY 2003 VL 41 IS 11 BP 1271 EP 1276 DI 10.1016/S0005-7967(03)00032-9 PG 6 WC Psychology, Clinical SC Psychology GA 740CL UT WOS:000186383400002 PM 14527527 ER PT J AU Koch, AM Reynolds, F Kircher, MF Merkle, HP Weissleder, R Josephson, L AF Koch, AM Reynolds, F Kircher, MF Merkle, HP Weissleder, R Josephson, L TI Uptake and metabolism of a dual fluorochrome tat-nanoparticle in HeLa cells SO BIOCONJUGATE CHEMISTRY LA English DT Article ID VIVO PROTEIN TRANSDUCTION; IRON-OXIDE; MAGNETIC NANOPARTICLES; PLASMA-MEMBRANE; CELLULAR UPTAKE; BASIC DOMAIN; DELIVERY; PEPTIDE; DNA; PERMEABILITY AB The ability to use magnetic nanoparticles for cell tracking, or for the delivery of nanoparticle-based therapeutic agents, requires a detailed understanding of probe metabolism and transport. Here we report on the development and metabolism of a dual fluorochrome version of our tat-CLIO nanoparticle termed Tat(FITC)-Cy3.5-CLIO. The nanoparticle features an FITC label on the tat peptide and a Cy3.5 dye directly attached to the cross-linked coating of dextran. This nanoparticle was rapidly internalized by HeLa cells, labeling 100% of cells in 45 min, with the amount of label per cell increasing linearly with time up to 3 h. Cells loaded with nanoparticles for 1 h retained 40-60% of their FITC and Cy3.5 labels over a period of 72 h in label-free media. Over a period of 144 h, or approximately 3.5 cell divisions, the T2 spin-spin relaxation time of cells was not significantly changed, indicating retention of the iron oxide among the dividing cell population. Using confocal microscopy and unfixed cells, both dyes were nuclear and perinuclear (broadly cytoplasmic) after Tat(FITC)-Cy3.5-CLIO labeling. Implications of the rapid labeling and slow excretion of the Tat(FITC)-Cy3.5-CLIO nanoparticle are discussed for cell tracking and drug delivery applications. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Swiss Fed Inst Technol, Dept Chem & Appl Biosci, CH-8057 Zurich, Switzerland. RP Josephson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Merkle, Hans/A-4381-2014 FU NCI NIH HHS [R01CA86782] NR 25 TC 99 Z9 104 U1 2 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 2003 VL 14 IS 6 BP 1115 EP 1121 DI 10.1021/bc034123v PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 746BD UT WOS:000186725700007 PM 14624624 ER PT J AU Perlis, RH Mischoulon, D Smoller, JW Wan, YJY Lamon-Fava, S Lin, KM Rosenbaum, JF Fava, M AF Perlis, RH Mischoulon, D Smoller, JW Wan, YJY Lamon-Fava, S Lin, KM Rosenbaum, JF Fava, M TI Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression; serotonin transporter; fluoxetine; insomnia; agitation; adverse event ID SOCIAL RHYTHM DISRUPTION; STRESSFUL LIFE EVENTS; BIPOLAR DEPRESSION; SLEEP-DEPRIVATION; FUNCTIONAL POLYMORPHISM; INDUCED AKATHISIA; PROTEIN GENE; RATING-SCALE; PAROXETINE; PROMOTER AB Background: The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been associated with poorer antidepressant response in major depressive disorder (MDD) and with antidepressant-induced mania. This study investigated a possible association with treatment-emergent insomnia or agitation. Methods: Thirty-six outpatients with MDD were genotyped at 5HTTLPR and treated with open-label fluoxetine up to 60 mg/day. Treatment-emergent adverse effects were assessed at each study visit. Results: Of nine subjects homozygous for the "S" allele, seven (78%) developed new or worsening insomnia, versus 6 of 27 (22%) non- "S"-homozygous subjects (Fisher's exact p =.005). Similarly, six of nine subjects homozygous for the "S " allele (67%) developed agitation, versus 2 of 27 (7%) of non-"S"-homozygous subjects (Fisher's exact p =.001). Conclusions: The "S" allele of the 5HTTLPR may identify patients at risk for developing insomnia or agitation with fluoxetine treatment. This preliminary result requires confirmation in larger samples. (C) 2003 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harbor UCLA Med Ctr, Dept Psychiat, Los Angeles, CA USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Boston, MA 02111 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. FU NIAAA NIH HHS [R01 AA12081]; PHS HHS [R10-MG56057] NR 35 TC 117 Z9 122 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2003 VL 54 IS 9 BP 879 EP 883 DI 10.1016/S0006-3223(03)00424-4 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 734NH UT WOS:000186062000003 PM 14573314 ER PT J AU Yaffe, K Edwards, ER Lui, LY Zmuda, JM Ferrell, RE Cauley, JA AF Yaffe, K Edwards, ER Lui, LY Zmuda, JM Ferrell, RE Cauley, JA TI Androgen receptor CAG repeat polymorphism is associated with cognitive function in older men SO BIOLOGICAL PSYCHIATRY LA English DT Article DE androgen receptor; CAG repeat; polymorphism; cognitive decline; older men ID GENE; HIPPOCAMPUS; EXPRESSION; CORTEX; MEMORY; CELLS; BRAIN AB Background: Androgen receptors are located throughout the brain, especially in regions involved with learning and memory. Different lengths of a CAG (glutamine) repeat polymorphism in exon 1 of the androgen receptor gene may influence androgen action, with longer repeat lengths conferring decreased androgen sensitivity. Methods: We sought to determine if this CAG polymorphism was associated with cognition in older men. Results: Among 301 community-dwelling white men (mean age, 73.0 +/- 7.1), greater CAG repeat length was associated with lower scores on three cognitive tests (p < .05 for all). In addition, 12 participants (9.8%) had cognitive impairment in the low tertile of CAG repeat length whereas 29 (16.3%) had cognitive impairment in the two higher tertiles (odds ratio = 1.8; 95% confidence interval = .9-3.7). Conclusions: Research should be directed at identifying the mechanism for this association and to determine if treatment with testosterone prevents cognitive decline. (C) 2003 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, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St, San Francisco, CA 94121 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [K23-AG00888]; NIAMS NIH HHS [P60-AR44811] NR 18 TC 40 Z9 40 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 NOV 1 PY 2003 VL 54 IS 9 BP 943 EP 946 DI 10.1016/S0006-3223(03)00115-X PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 734NH UT WOS:000186062000012 PM 14573323 ER PT J AU Vaiva, G Ducrocq, F Jezequel, K Averland, B Lestavel, P Brunet, A Marmar, CR AF Vaiva, G Ducrocq, F Jezequel, K Averland, B Lestavel, P Brunet, A Marmar, CR TI Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma SO BIOLOGICAL PSYCHIATRY LA English DT Article DE posttraumatic stress disorder; immediate treatment; propranolol; peritraumatic distress; short-term outcome ID PTSD AB Background: This study investigated the efficacy of propranolol prescribed shortly after trauma exposure in the prevention of posttraumatic stress disorder (PTSD) symptoms and diagnosis. Methods: Eleven patients received 40 mg of propranolol 3 times daily for 7 days, followed by a taper period of 8-12 days. They were compared with eight patients who refused propranolol but agreed to participate in the study. Though nonrandomized, the two groups did not differ on demographics, exposure characteristics, physical injury severity, or peritraumatic emotional responses. Results: Posttraumatic stress disorder rates were higher in the group who refused propranolol (318) compared with those who received the medication (1/11), as were the levels of PTSD symptoms (U = 85, p = .037). Conclusions: Our results are consistent with earlier findings and suggest that propranolol may be useful for mitigating PTSD symptoms or perhaps even preventing the development of PTSD. (C) 2003 Society of Biological Psychiatry. C1 Univ Lille 2, Clin Sch Psychiat, Lille, France. McGill Univ, Dept Psychiat, Montreal, PQ, Canada. Douglas Hosp, Res Ctr, Montreal, PQ, Canada. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Vaiva, G (reprint author), CHRU, Clin Michel Fontan, 6 Rue Prof Laguesse, F-59037 Lille, France. RI DUCROCQ, Francois/O-7342-2014; VAIVA, Guillaume/J-8983-2015 OI DUCROCQ, Francois/0000-0002-0664-761X; VAIVA, Guillaume/0000-0003-2462-008X NR 14 TC 274 Z9 281 U1 4 U2 22 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 NOV 1 PY 2003 VL 54 IS 9 BP 947 EP 949 DI 10.1016/S0006-3223(03)00412-8 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 734NH UT WOS:000186062000013 PM 14573324 ER PT J AU Morris, JP Berghmans, S Zahrieh, D Neuberg, DS Kanki, JP Look, AT AF Morris, JP Berghmans, S Zahrieh, D Neuberg, DS Kanki, JP Look, AT TI Zebrafish sperm cryopreservation with N,N-dimethylacetamide SO BIOTECHNIQUES LA English DT Article ID FISH SPERMATOZOA; FERTILIZATION; EGG AB High fecundity, rapid generation time, and external development of optically clear embryos make the zebrafish (Danio rerio) a convenient vertebrate model for genetic, developmental, and disease studies. Efficient sperm cryopreservation enhances the zebrafish model system by optimizing productive use of facility space, extending the reproductive lifetime of males, providing an alternative to live stocks for strain recovery, and ensuring the survival of valuable mutant lines. Here we identify a cryoprotective medium, 10% N,N-dimethylacetamide (DMA) (v/v) diluted in buffered sperm motility-inhibiting solution (BSMIS), as well as parameters for zebrafish sperm cryopreservation that enhance cryopreservation efficiency and significantly increase the yield of live embryos,from archived stocks. Our experiments emphasize the effect of the ratio of sperm and medium. volume and the use of large egg clutches to maximize the recovery of viable embryos. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 630,44 Binney St, Boston, MA 02115 USA. OI Berghmans, Stephane/0000-0001-5414-8674 FU NCI NIH HHS [CA21765, CA68484] NR 26 TC 24 Z9 27 U1 1 U2 4 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD NOV PY 2003 VL 35 IS 5 BP 956 EP + PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 744QL UT WOS:000186643500010 PM 14628669 ER PT J AU Maecker, B Sherr, DH Vonderheide, RH von Bergwelt-Baildon, MS Hirano, N Anderson, KS Xia, ZN Butler, MO Wucherpfennig, KW O'Hara, C Cole, G Kwak, SS Ramstedt, U Tomlinson, AJ Chicz, RM Nadler, LM Schultze, JL AF Maecker, B Sherr, DH Vonderheide, RH von Bergwelt-Baildon, MS Hirano, N Anderson, KS Xia, ZN Butler, MO Wucherpfennig, KW O'Hara, C Cole, G Kwak, SS Ramstedt, U Tomlinson, AJ Chicz, RM Nadler, LM Schultze, JL TI The shared tumor-associated antigen cytochrome P4501B1 is recognized by specific cytotoxic T cells SO BLOOD LA English DT Article ID 1B1 MESSENGER-RNA; LYMPHOCYTE RESPONSE; DENDRITIC CELLS; EXPRESSION; CYP1B1; CANCER; IDENTIFICATION; PEPTIDES; P450CYP1B1; GENERATION AB Cytochrome P450 1B1 (CYP1B1), a drug-metabolizing extrahepatic enzyme, was recently shown to be overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for anticancer therapy, particularly cancer immunotherapeutics. We identified HLA-A*0201-binding peptides and a naturally processed and presented T-cell epitope capable of inducing CYP1B1-specific cytotoxic T lymphocytes (CTLs) in HLA-A2 transgenic mice. Furthermore, the induction of CYP1B1-specific T cells was demonstrated in healthy donors and cancer patients. These T cells efficiently lysed target cells pulsed with the cognate peptide. More important, HLA-A2-matched tumor cell lines and primary malignant cells were also recognized by CYP1B1-specific CTLs. These findings form the basis of a phase 1 clinical trial exploring a DNA-based vector encoding CYP1B1 for widely applicable cancer immunotherapy conducted at the Dana-Farber Cancer Institute. (C) 2003 by The American Society of Hematology. C1 Univ Cologne, Dept Hematol & Oncol, D-50924 Cologne, Germany. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Pathol & Lab Med, Boston, MA 02215 USA. Zycos Inc, Lexington, MA USA. RP Schultze, JL (reprint author), Univ Cologne, Dept Hematol & Oncol, Joseph Stelzmann Str 9,Haus 16, D-50924 Cologne, Germany. RI Schultze, Joachim/D-7794-2011; OI Schultze, Joachim/0000-0003-2812-9853; Sherr, David/0000-0003-3353-0553 FU NCI NIH HHS [K08-CA-87720-01, K08-CA-88444-01, P01-CA-66966, P01-CA-78378]; PHS HHS [R01-06-086] NR 45 TC 54 Z9 56 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2003 VL 102 IS 9 BP 3287 EP 3294 DI 10.1182/blood-2003-05-1374 PG 8 WC Hematology SC Hematology GA 736BA UT WOS:000186149400038 PM 12869499 ER PT J AU Huettner, CS Koschmieder, S Iwasaki, H Iwasaki-Arai, J Radomska, HS Akashi, K Tenen, DG AF Huettner, CS Koschmieder, S Iwasaki, H Iwasaki-Arai, J Radomska, HS Akashi, K Tenen, DG TI Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; POLYMERASE-CHAIN-REACTION; INTERFERON-ALPHA THERAPY; BCR-ABL TRANSCRIPTS; TRANSGENIC MICE; RESIDUAL DISEASE; MAMMALIAN-CELLS; BONE-MARROW; IN-VIVO AB The BCR/ABL fusion protein is found in more than 90% of patients with chronic myeloid leukemia (CML) as well as in a subset of patients with acute B-cell leukemia. We have previously described a transgenic model for an inducible and reversible acute B-cell leukemia caused by p210 BCR/ABL. Here, we describe a new model of an inducible BCR/ABL disease by directing the expression of the oncogene to megakaryocytic progenitor cells within the murine bone marrow using the tetracycline-responsive expression system under the control of human CD34 regulatory elements. The predominant feature was the development of a chronic thrombocytosis. The condition progressed with the development of splenomegaly accompanied by lymphadenopathy in some mice. Affected animals demonstrated a dramatic increase in the number of megakaryocytes in the bone marrow and the spleen. Immunohistochemistry demonstrated that the reporter gene was expressed in hematopoietic stem cells (HSCs), common myeloid progenitor (CMP) cells, as well as in megakaryocytic/erythroid progenitor cells (MEPs). Although these mice did not display the increase in granulopoiesis commonly found in chronic myeloid leukemia (CML), the phenotype closely resembles a myeloproliferative disorder affecting the megakaryocytic lineage observed in some patients with the BCR/ABL P210 translocation. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Inst Med, 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, Sch Med, Inst Med, Rm 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. OI Tenen, Daniel/0000-0002-6423-3888 FU NIDDK NIH HHS [DK48 660] NR 47 TC 35 Z9 37 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2003 VL 102 IS 9 BP 3363 EP 3370 DI 10.1182/blood-2003-03-0768 PG 8 WC Hematology SC Hematology GA 736BA UT WOS:000186149400049 PM 12855552 ER PT J AU Chauhan, D Li, GL Hideshima, T Podar, K Mitsiades, C Mitsiades, N Catley, L Tai, YT Hayashi, T Shringarpure, R Burger, R Munshi, N Ohtake, Y Saxena, S Anderson, KC AF Chauhan, D Li, GL Hideshima, T Podar, K Mitsiades, C Mitsiades, N Catley, L Tai, YT Hayashi, T Shringarpure, R Burger, R Munshi, N Ohtake, Y Saxena, S Anderson, KC TI Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance SO BLOOD LA English DT Article ID HEAT-SHOCK-PROTEIN; HUMAN CARCINOMA-CELLS; NF-KAPPA-B; CYTOCHROME-C; THERAPEUTIC IMPLICATIONS; OLIGONUCLEOTIDE ARRAYS; HEAT-SHOCK-PROTEIN-27 HSP27; NEGATIVE REGULATOR; DRUG-RESISTANCE; APOPTOSIS AB Smac, second mitochondria-derived activator of caspases, promotes apoptosis via activation of caspases. Heat shock protein 27 (Hsp27) negatively regulates another mitochondrial protein, cytochrome c, during apoptosis; however, the role of Hsp27 in modulating Smac release is unknown. Here we show that Hsp27 is overexpressed in both dexamethasone (Dex)-resistant multiple myeloma (MM) cell lines (MM.1R, U266, RPMI-8226) and primary patient cells. Blocking Hsp27 by an antisense (AS) strategy restores the apoptotic response to Dex in Dex-resistant MM cells by triggering the release of mitochondrial protein Smac, followed by activation of caspase-9 and caspase-3. Moreover, AS-Hsp27 overcomes interleukin-6 (IL-6)-mediated protection against Dex-induced apoptosis. These data demonstrate that Hsp27 inhibits the release of Smac, and thereby confers Dex resistance in MM cells. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Asahi Breweries Ltd, Tokyo, Japan. Lovelace Resp Res Inst, Albuquerque, NM USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 56 TC 101 Z9 111 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 NOV 1 PY 2003 VL 102 IS 9 BP 3379 EP 3386 DI 10.1182/blood-2003-05-1417 PG 8 WC Hematology SC Hematology GA 736BA UT WOS:000186149400051 PM 12855565 ER PT J AU Jedlickova, K Stockton, DW Prchal, JT AF Jedlickova, K Stockton, DW Prchal, JT TI Possible primary familial and congenital polycythemia locus at 7q22.1-7q22.2 SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article ID ERYTHROPOIETIN RECEPTOR GENE; DOMINANT PRIMARY POLYCYTHEMIA; ERYTHROID PROGENITORS; LINKAGE ANALYSIS; ACTIVATION; MUTATION; ERYTHROCYTOSIS; DIMERIZATION AB Primary familial and congenital polycythemia (PFCP), inherited as an autosomal dominant trait, has been reported to be associated with mutations in the gene encoding the erythropoietin receptor (EpoR). The clinical features include the presence of isolated erythrocytosis, low erythropoietin (Epo) levels, normal hemoglobin-oxygen dissociation curve, hypersensitivity of erythroid progenitors to exogenous Epo in vitro and no progression to leukemia or myelodysplastic syndrome. Less than 15% of PFCP families have an identifiable EPOR mutation. Abnormalities of other genes are therefore likely responsible for the phenotype of the majority PFCP patients. In this study we report a family segregating PFCP with an autosomal dominant pattern of inheritance, where 7 of 14 members of the family were affected in four generations. This family was studied previously and an EPOR mutation was ruled out by sequencing and by genetic means. Here, we confirmed by linkage analysis that the disease phenotype was not linked to the Epo and EPOR genes. We then performed a genomewide screen with 410 polymorphic markers at average spacing 7.67 cM to locate the chromosomal region responsible for PFCP. We identified a region in 7q22.1-7q22.2 with a suggestive LOD score of 1.84, from our data this is the most likely location of a candidate region responsible for PFCP in this family. (C) 2003 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Texas Med Ctr, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX 77030 USA. RP Prchal, JT (reprint author), Baylor Coll Med, Texas Med Ctr, 1 Baylor Plaza,MS 525D, Houston, TX 77030 USA. NR 23 TC 10 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD NOV-DEC PY 2003 VL 31 IS 3 BP 327 EP 331 DI 10.1016/S1079-9796(03)00167-0 PG 5 WC Hematology SC Hematology GA 748DD UT WOS:000186846200006 PM 14636647 ER PT J AU Mitchell, BD Kammerer, CM Schneider, JL Perez, R Bauer, RL AF Mitchell, BD Kammerer, CM Schneider, JL Perez, R Bauer, RL TI Genetic and environmental determinants of bone mineral density in Mexican Americans: results from the San Antonio Family Osteoporosis Study SO BONE LA English DT Article DE bone mineral density; osteoporosis; heritability; family study; Mexican Americans ID ETHNIC-DIFFERENCES; PHYSICAL-ACTIVITY; PEDIGREE ANALYSIS; HIP FRACTURE; US ADULTS; MASS; EXTENSIONS; WOMEN; RISK; TWIN AB Osteoporosis is a major cause of disability in the United States. Numerous factors contribute to the decline in bone mineral density (BMD) that characterizes this disease, and the importance of heredity is now widely appreciated. We evaluated the joint contributions of genes and environmental factors on variation in BMD in 895 participants of the San Antonio Family Osteoporosis Study (SAFOS). Participants of the SAFOS ranged in age from 18 to 96 years and were members of 34 large families of Mexican American ancestry. BMD was measured at the spine, hip, and forearm by dual-energy X-ray absorptiometry. Information about medical history, lifestyle habits, dietary intake, and physical activity patterns was obtained by questionnaire. Age and body mass index were strongly associated with BMD at nearly every site; these and other measured risk factors accounted in aggregate for up to 46% of the total variation in BMD. In general, the environmental risk factors accounted for proportionately more of the total variation in BMD in men than in women. Genes accounted for 65-80% of the residual variation in spine and hip BMD, and 25-55% of the residual variability in forearm BMD. Although residual heritabilities were generally comparable between men and women across all ages combined, heritabilities at all sites tended to be higher in premenopausal women than in men younger than 50 years of age. Identifying the individual genes involved will shed insights into the processes that govern bone remodeling and may suggest strategies for the prevention of osteoporosis. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Mitchell, BD (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, 660 W Redwood St,Room 492, Baltimore, MD 21201 USA. OI Mitchell, Braxton/0000-0003-4920-4744 FU NCRR NIH HHS [M01-RR-01346]; NHLBI NIH HHS [P01-HL45522]; NIAMS NIH HHS [R01-AR43351] NR 32 TC 42 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD NOV PY 2003 VL 33 IS 5 BP 839 EP 846 DI 10.1016/S8756-3282(03)00246-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746XF UT WOS:000186772400011 PM 14623060 ER PT J AU Schmahmann, JD AF Schmahmann, JD TI Unbundling the cerebellum: Dysmetria of thought and the universal cerebellar transform SO BRAIN AND COGNITION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD NOV PY 2003 VL 53 IS 2 BP 102 EP 102 DI 10.1016/S0278-2626(03)00083-6 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 744QN UT WOS:000186643700001 ER PT J AU Ludtke, CB Coutinho, ML Jouglard, SDD Moreira, CN Fernandes, CHP Brod, CS Haake, DA Ko, AI Dellagostin, OA Aleixo, JAG AF Luedtke, Charli Beatriz Coutinho, Mariana Loner Dorneles Jouglard, Sandra Denise Moreira, Cecilia Nunes Pinho Fernandes, Claudia Hartleben Brod, Claudiomar Soares Haake, David A. Ko, Albert Icksang Dellagostin, Odir Antonio Guimaraes Aleixo, Jose Antonio TI MONOCLONAL ANTIBODIES AGAINST AN OUTER MEMBRANE PROTEIN FROM PATHOGENIC LEPTOSPIRA SO BRAZILIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE leptospirosis; monoclonal antibodies; LipL32 AB Two hybridomas secreting monoclonal antibodies (MAbs) that react with a lipoprotein (LipL32) of the outer membrane of pathogenic Leptospira were obtained. For hybridoma production, spleen cells from BALB/c mice imunized with recombinant LipL32 (rLipL32) were fused to SP2/O-Ag14 cells, selected in HAT medium and screened in an indirect ELISA. One MAb produced was of the IgG2b isotype and the other was an IgM. MAbs specificity was confirmed by indirect ELISA and immunoblotting using purified rLipL32 and whole-cell antigen preparations from Escherichia coli (E. coli) expressing LipL32 and from pathogenic and nonpathogenic serovars. Both Mabs reacted with most of the pathogenic serovars tested and none reacted with non-pathogenic Leptospira. The MAbs described have potential for use in diagnostic tests for leptospirosis. C1 [Luedtke, Charli Beatriz; Coutinho, Mariana Loner; Dorneles Jouglard, Sandra Denise; Moreira, Cecilia Nunes; Pinho Fernandes, Claudia Hartleben; Dellagostin, Odir Antonio; Guimaraes Aleixo, Jose Antonio] Univ Fed Pelotas, Ctr Biotecnol, BR-96019900 Pelotas, RS, Brazil. [Brod, Claudiomar Soares] Univ Fed Pelotas, Ctr Control Zoonoses, BR-96019900 Pelotas, RS, Brazil. [Haake, David A.] Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Ko, Albert Icksang] Fundacao Oswaldo Cruz, Ctr Pesquisa Goncalo Moniz, Salvador, BA, Brazil. [Dellagostin, Odir Antonio] Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, New York, NY 10021 USA. RP Aleixo, JAG (reprint author), Univ Fed Pelotas, Ctr Biotecnol, Campus Univ Capao Leao S-N, BR-96019900 Pelotas, RS, Brazil. RI Dellagostin, Odir/C-2331-2009; Coutinho, Mariana/J-9024-2012; Ko, Albert/P-2343-2015 OI Dellagostin, Odir/0000-0003-2803-4088; NR 12 TC 5 Z9 5 U1 0 U2 3 PU SOC BRASILEIRA MICROBIOLOGIA PI SAO PAULO PA AV PROF LINEU PRESTES,1374, 05508 SAO PAULO, BRAZIL SN 1517-8382 EI 1678-4405 J9 BRAZ J MICROBIOL JI Braz. J. Microbiol. PD NOV PY 2003 VL 34 SU 1 BP 1 EP 4 DI 10.1590/S1517-83822003000500001 PG 4 WC Microbiology SC Microbiology GA V04NQ UT WOS:000207065500001 ER PT J AU Tischkowitz, M Ameziane, N Waisfisz, Q De Winter, JP Harris, R Taniguchi, T D'Andrea, A Hodgson, SV Mathew, CG Joenje, H AF Tischkowitz, M Ameziane, N Waisfisz, Q De Winter, JP Harris, R Taniguchi, T D'Andrea, A Hodgson, SV Mathew, CG Joenje, H TI Bi-allelic silencing of the Fanconi anaemia gene FANCF in acute myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Fanconi anemia; acute myeloid leukaemia; FANCF; silencing; chromosomal instability ID BRCA PATHWAY; CHROMOSOME-11; PROTEIN AB Fanconi anaemia (FA) is a chromosomal instability disorder associated with a high risk of acute myeloid leukaemia (AML). Previous work has shown that the AML cell line CHRF-288, derived from a sporadic AML-M7 patient, does not express FANCF protein and exhibits a cellular FA phenotype. We show that this phenotype is corrected by a FANCF-expressing plasmid and that the absence of FANCF protein is explained by hypermethylation of the promoter region of the FANCF gene. As FANCF is localized in a hot-spot region for somatic hypermethylation (11p15), FANCF silencing might be an early step in sporadic carcinogenesis, including leukaemogenesis. C1 VU Univ, Med Ctr, Dept Clin Genet & Human Genet, NL-1081 BT Amsterdam, Netherlands. Guys Hosp, Guys Kings & St Thomass Sch Med, Univ London Kings Coll, Dept Med & Mol Genet,Div Genet & Dev, London SE1 9RT, England. Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA USA. RP Joenje, H (reprint author), VU Univ, Med Ctr, Dept Clin Genet & Human Genet, Van der Boechorststr, NL-1081 BT Amsterdam, Netherlands. RI Mathew, Christopher/G-3434-2015 OI Mathew, Christopher/0000-0003-4178-1838 NR 12 TC 42 Z9 43 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2003 VL 123 IS 3 BP 469 EP 471 DI 10.1046/j.1365-2141.2003.04640.x PG 3 WC Hematology SC Hematology GA 734HE UT WOS:000186048600013 PM 14617007 ER PT J AU Berman, J Hsu, K Look, AT AF Berman, J Hsu, K Look, AT TI Zebrafish as a model organism for blood diseases SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE zebrafish; mutagenesis screen; haematopoiesis; transgenesis ID AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; TRANSGENIC ZEBRAFISH; DANIO-RERIO; INSERTIONAL MUTAGENESIS; MORPHOLINO PHENOCOPIES; HEMATOPOIETIC LINEAGES; VERTEBRATE DEVELOPMENT; VASCULAR DEVELOPMENT; MYELOID DEVELOPMENT; CELL MIGRATION C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Mayer 630, Boston, MA 02115 USA. FU NICHD NIH HHS [K12-HD00850] NR 82 TC 24 Z9 27 U1 0 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2003 VL 123 IS 4 BP 568 EP 576 DI 10.1046/j.1365-2141.2003.04682.x PG 9 WC Hematology SC Hematology GA 740RP UT WOS:000186415600001 PM 14616958 ER PT J AU Vajpayee, RB Mukerji, N Tandon, R Sharma, N Pandey, RM Biswas, NR Malhotra, N Melki, SA AF Vajpayee, RB Mukerji, N Tandon, R Sharma, N Pandey, RM Biswas, NR Malhotra, N Melki, SA TI Evaluation of umbilical cord serum therapy for persistent corneal epithelial defects SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID AMNIOTIC MEMBRANE TRANSPLANTATION; STEM-CELL DEFICIENCY; NERVE GROWTH-FACTOR; AUTOLOGOUS SERUM; LIMBAL TRANSPLANTATION; TOPICAL FIBRONECTIN; TARSORRHAPHY; ULCERATION; COLLAGEN AB Aims: To evaluate umbilical cord serum therapy as a means of promoting the healing of persistent corneal epithelial defects. Methods: Umbilical cord serum or autologous serum drops were used to promote the healing of persistent epithelial defects. The study design was a prospective randomised controlled clinical trial. 60 eyes of 59 patients were divided into two groups, 31 in the cord serum group and 29 in the autologous serum control group. Epithelial defects measuring at least 2 mm in linear dimension resistant to conventional medical management were included. Serial measurements of the size of the epithelial defects-namely, two maximum linear dimensions perpendicular to each other, and the area and perimeter was done at start of therapy and follow up days 3, 7, 14, 21. Rate of healing of the epithelial defects were measured as percentage decrease from the baseline parameter at each subsequent follow up. The data were analysed by the non-parametric Wilcoxon rank sum test using STATA 7.0. Results: The median percentage decrease in the size of the epithelial defect was significantly greater in the cord serum group at days 7, 14 and 21 (p<0.05) when measured in terms of the area and perimeter. A greater number of patients showed complete re-epithelialisation with umbilical cord serum (n = 18) than with autologous serum ( n = 11) (Pearson χ = 0.19). None of the patients reported any side effects or discomfort with either treatment. Conclusions: Umbilical cord serum leads to faster healing of the persistent corneal epithelial defects refractory to all medical management compared to autologous serum. C1 All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Ocular Pharmacol, New Delhi 110029, India. All India Inst Med Sci, Dept Biostat, New Delhi 110029, India. All India Inst Med Sci, Dept Obstet & Gynaecol, New Delhi 110029, India. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Vajpayee, RB (reprint author), All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Dept Ocular Pharmacol, New Delhi 110029, India. NR 32 TC 48 Z9 50 U1 0 U2 1 PU B M J PUBLISHING 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 NOV PY 2003 VL 87 IS 11 BP 1312 EP 1316 DI 10.1136/bjo.87.11.1312 PG 5 WC Ophthalmology SC Ophthalmology GA 741UP UT WOS:000186479000003 PM 14609821 ER PT J AU Saksena, M Harisinghani, MG Wittenberg, J Mueller, PR AF Saksena, M Harisinghani, MG Wittenberg, J Mueller, PR TI Hepatic portal venous gas: transient radiographic finding associated with colchicine toxicity SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID CLINICAL-SIGNIFICANCE; BARIUM ENEMA; VEIN GAS; GRANULOMATOUS COLITIS; CT FINDINGS; SYSTEM AB Hepatic portal venous gas has traditionally been associated with a grave prognosis and high mortality. However, with the advent of ultrasound and CT, numerous less serious causes have been associated with this dramatic radiological finding. We present a previously unreported association with colchicine toxicity. The patient ingested a large dose of colchicine and was subsequently found to have portal venous gas on CT. The source of gas was felt to be intestinal gas penetrating through the demonstrated bowel injury. No surgical intervention was deemed necessary and the finding resolved spontaneously. C1 Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02135 USA. Harvard Univ, Sch Med, Boston, MA 02135 USA. RP Saksena, M (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02135 USA. NR 25 TC 6 Z9 8 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 NOV PY 2003 VL 76 IS 911 BP 835 EP 837 DI 10.1259/bjr/13712140 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 749CZ UT WOS:000186902200012 PM 14623787 ER PT J AU Firth, PG Tsuruta, Y Kamath, Y Dzik, WH Ogilvy, CS Peterfreund, RA AF Firth, PG Tsuruta, Y Kamath, Y Dzik, WH Ogilvy, CS Peterfreund, RA TI Transfusion-related acute lung injury or acute chest syndrome of sickle cell disease? A case report SO CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article AB Purpose: To describe how to differentiate transfusion-related acute lung injury from acute chest syndrome of sickle cell disease. Clinical features: A neurosurgical patient with sickle cell disease received two units of packed red blood cells postoperatively. Four hours later she developed progressive respiratory distress, diffuse geographical airspace disease and bilateral pulmonary edema. The patient recovered sufficiently to be transferred from the intensive care unit within four days. The temporal relationship to transfusion, features on computerized tomographic scan, and the rapid resolution of severe edema point to a diagnosis of transfusion related acute lung injury Granulocyte or human leukocyte antigen antibodies in donor plasma may confirm a diagnosis of transfusion injury. Conclusion: The clinician should appreciate that erythrocyte transfusion to prevent or treat acute chest syndrome may cause transfusion related acute lung injury, a condition that mimics, exacerbates or possibly triggers the syndrome it was intended to treat. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02115 USA. RP Firth, PG (reprint author), Radcliffe Infirm, Nuffield Dept Anaesthet, Woodstock Rd, Oxford OX2 6HE, England. NR 14 TC 7 Z9 8 U1 0 U2 0 PU CANADIAN ANESTHESIOLOGISTS SOC PI TORONTO PA 1 EGLINTON AVE EAST, SUITE 208, TORONTO, ONTARIO M4P 3A1, CANADA SN 0832-610X J9 CAN J ANAESTH JI Can. J. Anaesth.-J. Can. Anesth. PD NOV PY 2003 VL 50 IS 9 BP 895 EP 899 PG 5 WC Anesthesiology SC Anesthesiology GA 748LF UT WOS:000186862800006 PM 14617585 ER PT J AU Fisher, CM AF Fisher, CM TI Early arrest of mental and motor development associated with bilateral hippocampal anoxic damage SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article AB Background: Clinical-pathological study of the case of a woman with amentia from birth. Case history: A 45-year-old woman was institutionalized since the age of two and showed no change in 43 years. She did not stand, walk, talk, use her hands or comprehend. She was placed in a chair each day. She lacked control of bladder and bowel. She showed no mental capability. Case pathology: The brain weighed 1250 gm and was normally developed. There were two anoxic-ischemic regions of damage. The hippocampus showed extensive damage bilaterally and the cerebellum showed watershed infarction bilaterally. Conclusion: A perinatal anoxic-ischemic episode is suspected. Hippocampal damage was the only finding that might explain the failure of mental and motor development. If this hypothesis is correct, the function of the human hippocampus is broader than currently accepted. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY, AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD NOV PY 2003 VL 30 IS 4 BP 375 EP 377 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 744WN UT WOS:000186656000014 PM 14672271 ER PT J AU Drezek, RA Richards-Kortum, R Brewer, MA Feld, MS Pitris, C Ferenczy, A Faupel, ML Follen, M AF Drezek, RA Richards-Kortum, R Brewer, MA Feld, MS Pitris, C Ferenczy, A Faupel, ML Follen, M TI Optical imaging of the cervix SO CANCER LA English DT Article; Proceedings Paper CT 2nd International Conference on Cervical Cancer CY APR 11-14, 2002 CL HOUSTON, TEXAS DE photonics; optical technology; detection; precancerous lesions; uterine cervix ID LASER-INDUCED FLUORESCENCE; MULTIVARIATE STATISTICAL ALGORITHM; MULTIPLE EXCITATION WAVELENGTHS; TIME CONFOCAL MICROSCOPY; IN-VIVO; SPECTROSCOPIC DIAGNOSIS; AMELANOTIC TISSUE; LIGHT-SCATTERING; CANCER; COLLAGEN AB Recent advances in fiber optics, sources and detectors, imaging, and computer-controlled instrumentation have stimulated a period of unprecedented growth in the development of photonics technologies for a wide variety of diagnostic and therapeutic clinical applications. These include the application of quantitative optical spectroscopy and imaging for the detection of precancerous lesions in the uterine cervix, a topic of interest at the Second International Conference on Cervical Cancer, which was held April 11-14, 2002. Investigators have applied the Littenberg method of emerging technology assessment to new optical methods used to detect cervical neoplasia. Currently, such technologies as fluorescence spectroscopy (the combination of fluorescence and diffuse reflectance spectroscopy), tri-modal spectroscopy, and light-scattering spectroscopy that probe the spectral characteristics of tissue are being investigated. Optical technologies that create images of subcellular structure without biopsy subsequent to pathology that currently are under investigation include in vivo confocal imaging and optical coherence tomography. Numerous small studies have demonstrated the potential of these optical technologies. What remains to be elucidated are the fundamental biophysical origins of variations in remitted optical signals between normal and dysplastic tissue. Large multicenter randomized controlled trials are needed to confirm the detection and imaging capabilities of optical technology. Furthermore, the development of contrast agents that could boost detection with these technologies is needed, and basic biologic characterization of signals should be pursued. Applying the Littenberg assessment will help ensure that superior, not simply alternative, technologies are implemented. (C) 2003 American Cancer Society. C1 Univ Texas, MD Anderson Canc Ctr, Ctr Biomed Engn, Dept Gynecol Oncol, Houston, TX 77030 USA. Rice Univ, Dept Bioengn, Houston, TX 77251 USA. Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. Arizona Hlth Sci Ctr, Arizona Canc Ctr, Tucson, AZ 85724 USA. MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Lab, Boston, MA 02114 USA. McGill Univ, Sir Mortimer B Davis Jewish Hosp, Dept Pathol, Montreal, PQ, Canada. SpectRx Inc, Norcross, VA USA. RP Follen, M (reprint author), Univ Texas, MD Anderson Canc Ctr, Ctr Biomed Engn, Dept Gynecol Oncol, 1515 Holcombe Blvd,Unit 193, Houston, TX 77030 USA. RI Drezek, Rebekah/A-5101-2012; Richards-Kortum, Rebecca/P-4074-2014; OI Richards-Kortum, Rebecca/0000-0003-2347-9467; Pitris, Costas/0000-0002-5559-1050 NR 44 TC 61 Z9 63 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2003 VL 98 IS 9 SU S BP 2015 EP 2027 DI 10.1002/cncr.11678 PG 13 WC Oncology SC Oncology GA 737ML UT WOS:000186236300004 PM 14603538 ER PT J AU Masutomi, K Hahn, WC AF Masutomi, K Hahn, WC TI Telomerase expression - Only half the story SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE haploinsufficiency; hTERT; DNA damage; telomere ID NORMAL HUMAN-CELLS; HUMAN TUMOR-CELLS; MAMMALIAN TELOMERES; IONIZING-RADIATION; IMMORTAL CELLS; LIFE-SPAN; CANCER; TUMORIGENESIS; INHIBITION; MICE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 710C, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu FU NCI NIH HHS [K01 CA94223] NR 37 TC 3 Z9 4 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV-DEC PY 2003 VL 2 IS 6 BP 685 EP 686 PG 2 WC Oncology SC Oncology GA 772MQ UT WOS:000188846200016 PM 14688477 ER PT J AU Huang, L Ren, R Hen, DS Li, YQ Kharbanda, S Kufe, D AF Huang, L Ren, R Hen, DS Li, YQ Kharbanda, S Kufe, D TI NO cytoplasmic domain coactivates Wnt target gene transcription and confers transformation SO CANCER BIOLOGY & THERAPY LA English DT Article DE MUC1; beta-catenin; Tcf4; cyclin D1; transcription; transformation ID CARCINOMA-ASSOCIATED ANTIGEN; BETA-CATENIN; CYCLIN D1; COLON-CARCINOMA; CELL-ADHESION; C-SRC; APC; PROTEIN; CANCER; ASSOCIATION AB The DF3/MUC1 mucin-like transmembrane oncoprotein is overexpressed by most human carcinomas. The MUC1 cytoplasmic domain (CD) binds directly to the Writ effector, beta-catenin, and colocalizes with beta-catenin in the nucleus; however, the nuclear function of MUC1 is unknown. The present results demonstrate that MUC1 coactivates transcription of beta-catenin-Tcf-binding sites in the pTOPFLASH reporter. Activation of transcription was abrogated by expression of MUC1 with a Y-46 --> F mutation in the CD that attenuates binding of MUC1 and p-catenin. We also show that transcription of the Wnt responsive cyclin D1 promoter is activated by MUC1, but not MUC1 (Y46F), and that the cyclin D1 gene is upregulated in MUC1-positive cells. In concert with these results, MUC1-induced anchorage-independent growth and tumorigenicity were also abrogated by mutating MUC1 at the Y-46 site. These findings support a model in which the MUC 1 functions as a transforming protein by coactivating transcription of Writ target genes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. ILEX Prod Inc, Boston, MA USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA97098] NR 30 TC 78 Z9 80 U1 1 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV-DEC PY 2003 VL 2 IS 6 BP 702 EP 706 PG 5 WC Oncology SC Oncology GA 772MQ UT WOS:000188846200020 PM 14688481 ER PT J AU Cho, E Spiegelman, D Hunter, DJ Chen, WY Colditz, GA Willett, WC AF Cho, E Spiegelman, D Hunter, DJ Chen, WY Colditz, GA Willett, WC TI Premenopausal dietary carbohydrate, glycemic index, glycemic load, and fiber in relation to risk of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CORONARY-HEART-DISEASE; TOTAL-ENERGY-INTAKE; POSTMENOPAUSAL WOMEN; VITAMIN-C; COHORT; FAT; QUESTIONNAIRE; VEGETABLES; NUTRIENTS; URUGUAY AB Carbohydrate intake, glycemic index, and glycemic load have been hypothesized to increase risk of breast cancer by raising insulin levels, but these associations have not been studied extensively. The insulin response to dietary carbohydrate is substantially greater among overweight women than among leaner women. Although fiber intake has been hypothesized to reduce the risk of breast cancer, data from early adult life are lacking. We examined dietary carbohydrate, glycemic index, glycemic load, and fiber in relation to breast cancer risk among 90,655 premenopausal women in the Nurses' Health Study II aged 26-46 years in 1991. Diet was assessed with a food frequency questionnaire in 1991 and 1995. During 8 years of follow-up, we documented 714 incident cases of invasive breast cancer. Dietary carbohydrate intake, glycemic load, and glycemic index were not related to breast cancer risk in the overall cohort. However, the associations differed by body mass index (BMI): among women with BMI < 25 kg/m(2), the multivariate relative risks for the increasing quintiles of carbohydrate intake were 1.00 (referent), 0.87, 0.77, 0.66, and 0.62 [95% confidence interval, 0.40-0.97; P, test for trend = 0.02]; and among women with BMI greater than or equal to 25 kg/m(2), the corresponding relative risks were 1.00 (referent), 1.30, 135, 1.50, and 1.47 (95% confidence interval, 0.84-2.59; P, test for trend = 0.14; P, test for interaction = 0.02). Similar interaction with BMI was observed for glycemic load, but not for glycemic index. Intakes of total fiber and different types of fiber were not appreciably related to breast cancer risk. Our findings suggest that the associations between carbohydrate intake or glycemic load and breast cancer risk among young adult women differ by body weight. Our data do not support a strong association between fiber intake and breast cancer risk. C1 Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. RP Cho, E (reprint author), Harvard Univ, Sch Med, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA50385] NR 42 TC 77 Z9 78 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 BP 1153 EP 1158 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 750NB UT WOS:000187001700005 PM 14652274 ER PT J AU Liu, G Zhou, W Park, S Miller, DP Wain, JC Lynch, TJ Su, L Christiani, DC AF Liu, G Zhou, W Park, S Miller, DP Wain, JC Lynch, TJ Su, L Christiani, DC TI XRCC1 and ERCC2 Polymorphisms are associated with Barrett's esophagus risk. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 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 AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1280S EP 1281S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300019 ER PT J AU Wirth, L Moran, AE Weeks, L Krane, JE Norris, CM Haddad, RI Posner, MR Bertagnolli, MM AF Wirth, L Moran, AE Weeks, L Krane, JE Norris, CM Haddad, RI Posner, MR Bertagnolli, MM TI A pilot study of celecoxib in patients with oral premalignant lesions: Preliminary results. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1281S EP 1282S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300023 ER PT J AU Schernhammer, E Kang, JH Chan, AT Michaud, DS Skinner, HG Giovannucci, E Colditz, GA Fuchs, CS AF Schernhammer, E Kang, JH Chan, AT Michaud, DS Skinner, HG Giovannucci, E Colditz, GA Fuchs, CS TI A prospective study of aspirin use and risk of pancreatic cancer in women. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Channing Labs, Boston, MA USA. NCI, Nutr Epidemiol Branch, Rockville, MD USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Skinner, Halcyon/A-1049-2009; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1292S EP 1292S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300065 ER PT J AU Zhou, W Liu, G Park, S Miller, DR Wain, J Lynch, TJ Su, L Christiani, DC AF Zhou, W Liu, G Park, S Miller, DR Wain, J Lynch, TJ Su, L Christiani, DC TI MnSOD Ala16Val polymorphism modifies the association between Helicobacter pylori infection and the risk of esophageal adenocarcinoma. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1294S EP 1294S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300072 ER PT J AU Jiang, J Matranga, CB Cai, DP Latham, VM Zhang, XX Lowell, AM Martelli, F Shapiro, GI AF Jiang, J Matranga, CB Cai, DP Latham, VM Zhang, XX Lowell, AM Martelli, F Shapiro, GI TI Flavopiridol-induced apoptosis during S phase requires E2F-1 and inhibition of cyclin A-dependent kinase activity SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR E2F-1; CANCER CELL-LINES; RETINOBLASTOMA PROTEIN; DIFFERENTIAL REGULATION; ENDOTHELIAL-CELLS; TRANSFORMED-CELLS; CDK INHIBITORS; PHOSPHORYLATION; P53; EXPRESSION AB Transformed cells are selectively sensitized to apoptosis induced by the cyclin-dependent kinase inhibitor flavopiridol after their recruitment to S phase. During S phase, cyclin A-dependent kinase activity neutralizes E2F-1 allowing orderly S phase progression. Inhibition of cyclin A-dependent kinase by flavopiridol could cause inappropriately persistent E2F-1 activity during S phase traversal and exit. Transformed cells, with high baseline levels of E2F-1 activity, may be particularly sensitive to cyclin A-dependent kinase inhibition, as the residual level of E2F-1 activity that persists may be sufficient to induce apoptosis. Here, we demonstrate that flavopiridol treatment during S phase traversal results in persistent expression of E2F-1. The phosphorylation of E2F-1 is markedly diminished, whereas that of the retinoblastoma protein is minimally affected, so that E2F-1/DP-1 heterodimers remain bound to DNA. In addition, manipulation of E2F-1 levels leads to predictable outcomes when cells are exposed to flavopiridol during S phase. Tumor cells expressing high levels of ectopic E2F-1 are more sensitive to flavopiridol-induced apoptosis during S phase compared with parental counterparts, and high levels of ectopic E2F-1 expression are sufficient to sensitize nontransformed cells to flavopiridol. Furthermore, E2F-1 activity is required for flavopiridol-induced apoptosis during S phase, which is severely compromised in cells homozygous for a nonfunctional E2F-1 allele. Finally, the response to flavopiridol during S phase is blunted in cells expressing a nonphosphorylatable E2F-1 mutant incapable of binding cyclin A, suggesting that the modulation of E2F-1 activity produced by flavopiridol-mediated cyclin-dependent kinase inhibition is critical for the apoptotic response of S phase cells. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 810A,44 Binney St, Boston, MA 02115 USA. OI Martelli, Fabio/0000-0002-8624-7738 FU NCI NIH HHS [R01 CA090687, R01 CA 90687] NR 72 TC 31 Z9 33 U1 0 U2 1 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 NOV 1 PY 2003 VL 63 IS 21 BP 7410 EP 7422 PG 13 WC Oncology SC Oncology GA 742UA UT WOS:000186535400052 PM 14612540 ER PT J AU Chen, YH vanSonnenberg, E Urman, R Silverman, SG AF Chen, YH vanSonnenberg, E Urman, R Silverman, SG TI Lymphocele mimicking a pancreatic pseudocyst: Imaging characteristics and percutaneous management SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE lymphocele; interventional radiology; pancreas, pseudocyst; pancreas, surgery ID CYST FLUID ANALYSIS; DIFFERENTIAL-DIAGNOSIS; PELVIC LYMPHOCELES; DRAINAGE; TRANSPLANTATION; SCLEROTHERAPY; SCLEROSIS; NEOPLASMS AB Lymphocele can be a difficult diagnosis to establish and may be confused for other abdominal fluid collections. Conversely, pancreatic pseudocysts may occur inadvertently from upper abdominal surgery and must be included in the differential diagnosis of virtually all peripancreatic fluid collections. We report the unusual occurrence of an unsuspected postoperative peripancreatic lymphocele that was thought to be a pancreatic pseudocyst. In retrospect, CT findings were evident and diagnostic. The lymphocele responded well to percutaneous drainage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiol, Boston, MA 02115 USA. RP Chen, YH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiol, 44 Binney St, Boston, MA 02115 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD NOV-DEC PY 2003 VL 26 IS 6 BP 564 EP 566 DI 10.1007/s00270-003-2750-6 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765XL UT WOS:000188316300012 PM 15061184 ER PT J AU Liddicoat, JR Mac Neill, BD Gillinov, AM Cohn, WE Chin, CH Prado, AD Pandian, NG Oesterle, SN AF Liddicoat, JR Mac Neill, BD Gillinov, AM Cohn, WE Chin, CH Prado, AD Pandian, NG Oesterle, SN TI Percutaneous mitral valve repair: A feasibility study in an ovine model of acute ischemic mitral regurgitation SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article; Proceedings Paper CT 51st Annual Scientific Session of the American-College-of-Cardiology CY MAR 17-20, 2002 CL ATLANTA, GEORGIA SP Amer Coll Cardiol DE mitral valve repair; mitral regurgitation; percutaneous; annuloplasty ID LEFT-VENTRICULAR ISCHEMIA; DILATED CARDIOMYOPATHY; RING ANNULOPLASTY; REPLACEMENT; RECONSTRUCTION; COMMISSUROTOMY; CATHETER AB Annuloplasty is the cornerstone of surgical mitral valve repair. A percutaneous transvenous catheter-based approach for mitral valve repair was tested by placing a novel annuloplasty device in the coronary sinus of sheep with acute ischemic mitral regurgitation. Mitral regurgitation was reduced from 3-4+ to 0-1+ in all animals (P < 0.03). The annuloplasty functioned by reducing septal-lateral mitral annular diameter (30 +/- 2.1 mm preinsertion vs. 24 +/- 1.7 mm postinsertion; P < 0.03). These preliminary experiments demonstrate that percutaneous mitral annuloplasty is feasible. Further study is necessary to demonstrate long-term safety and efficacy of this novel approach. C1 Beth Israel Deaconess Med Ctr, Div Cardiac Surg, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44195 USA. Tufts New England Med Ctr, Div Cardiol, Boston, MA USA. RP Gillinov, AM (reprint author), Cleveland Clin Fdn F24, Dept Thorac & Cardiovasc Surg, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 18 TC 78 Z9 83 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV PY 2003 VL 60 IS 3 BP 410 EP 416 DI 10.1002/ccd.10662 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 738ZX UT WOS:000186318700020 PM 14571496 ER PT J AU Meier, B Palacios, I Windecker, S Rotter, M Cao, QL Keane, D Ruiz, CE Hijazi, ZM AF Meier, B Palacios, I Windecker, S Rotter, M Cao, QL Keane, D Ruiz, CE Hijazi, ZM TI Transcatheter left atrial appendage occlusion with Amplatzer devices to obviate anticoagulation in patients with atrial fibrillation SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE left atrial appendage occlusion; atrial fibrillation; stroke prevention ID NATIONAL PATTERNS; RHYTHM CONTROL; WARFARIN USE; STROKE; THROMBOEMBOLISM; OBLITERATION; PROPHYLAXIS AB It is assumed that over 90% of clinically apparent embolisms in atrial fibrillation originate from the left atrial appendage. Recently, a percutaneous method (PLAATO technique) to occlude the left atrial appendage to the end of preventing thromboembolic complications of atrial fibrillation has been introduced into clinical practice. This technique is quite intricate and requires general anesthesia. The Amplatzer atrial septal occluder lends itself for a more simple approach to this intervention. The first 16 patients treated at four centers are described. Their age varied from 58 to 83 years. All suffered from atrial fibrillation but eight of them were in sinus rhythm at the time of implantation. All but two procedures were done under local anesthesia of the groin only. There was one technical failure (device embolization) requiring surgery. All other patients left the hospital a day after the procedure without complications. There were no problems or embolic events during an overall follow-up of 5 patient-years and all left atrial appendages were completely occluded without evidence of thrombosis at the atrial side of the device at the latest follow-up echocardiography. With the Amplatzer technique, the left atrial appendage can be percutaneously occluded with a venous puncture under local anesthesia, without echocardiographic guidance, and at a reasonable risk. It remains to be evaluated in larger series or randomized trials how the simpler Amplatzer technique compares with the complex PLAATO technique, and whether left atrial appendage closure is competitive with oral anticoagulation with warfarin or the novel ximelagatran to prevent thromboembolism in atrial fibrillation. C1 Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Univ Hosp Boston, Boston, MA USA. Univ Chicago, Childrens Hosp, Chicago, IL 60637 USA. Univ Illinois, Chicago, IL USA. RP Meier, B (reprint author), Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland. NR 17 TC 112 Z9 125 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV PY 2003 VL 60 IS 3 BP 417 EP 422 DI 10.1002/ccd.10660 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 738ZX UT WOS:000186318700021 PM 14571497 ER PT J AU Ginns, LC Roberts, DH Mark, EJ Brusch, JL Marler, JJ AF Ginns, LC Roberts, DH Mark, EJ Brusch, JL Marler, JJ TI Pulmonary capillary hemangiomatosis with atypical endotheliomatosis - Successful antiangiogenic therapy with doxycycline SO CHEST LA English DT Article DE alpha-interferon; angiogenesis; antiangiogenic therapy; basic fibroblast growth factor; matrix metalloproteinases; pulmonary capillary hemangiomatosis ID ABDOMINAL AORTIC-ANEURYSMS; MATRIX METALLOPROTEINASES; HYPERTENSION; GROWTH; DISEASE; ANGIOGENESIS; PROSTACYCLIN; INHIBITION; EXPRESSION; MODEL AB We report here our experience in achieving remission in a 20-year-old man with pulmonary capillary hemangiomatosis (PCH) with atypical endotheliomatosis following therapy with doxycycline. PCH is a rare disorder characterized by proliferating capillaries that invade the pulmonary interstitium and alveolar septae, and occlude the pulmonary vasculature. The patient's symptoms, lung function, and radiographic findings had worsened despite treatment with both prednisone and alpha-interferon. He was considered to be a candidate for transplantation. Given the elevated levels of basic fibroblast growth factor (bFGF) in urine and the capillary proliferation noted on biopsy specimens, we elected to treat the patient with doxycycline, a matrix metalloproteinase and angiogenesis inhibitor. Following several weeks of therapy, a gradual resolution of symptoms was noted, with normalization of pulmonary function test results and urine bFGF levels. After 18 months of therapy, the patient remains in complete remission. C1 Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Childrens Hosp & Med Ctr, Dept Surg Res, Boston, MA USA. Cambridge Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ginns, LC (reprint author), Massachusetts Gen Hosp, Pulm Crit Care Unit, White 907, Boston, MA 02114 USA. NR 31 TC 37 Z9 40 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2003 VL 124 IS 5 BP 2017 EP 2022 DI 10.1378/chest.124.5.2017 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 743UH UT WOS:000186591600062 PM 14605083 ER PT J AU Koulmanda, M Qipo, A Auchincloss, H Smith, RN AF Koulmanda, M Qipo, A Auchincloss, H Smith, RN TI Effects of streptozotocin on autoimmune diabetes in NOD mice SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE autoimmunity; NOD mice; regulatory T cells; streptozotocin ID ISLET ALLOGRAFT-REJECTION; PANCREATIC-ISLETS; T-CELLS; MONOCLONAL-ANTIBODIES; NONDEPLETING ANTI-CD4; FETAL MOUSE; BETA-CELLS; TRANSPLANTATION; DESTRUCTION; BLOCKADE AB Non-obese diabetic (NOD) mice develop autoimmunity that destroys their native beta cells causing diabetes. Their autoimmunity will also destroy syngeneic transplanted islets and transfer both autoimmunity and diabetes via spleen cells to non-diabetic mice. In this report, we studied the effects of streptozotocin (STZ) on the autoimmune diabetes in NOD mice. We transplanted NOD.SCID islets into three groups of NOD mice: (1) spontaneously diabetic NOD mice (NOD-sp.); (2) prediabetic NOD mice made diabetic by streptozotocin (NOD-stz); and (3) diabetic NOD mice also treated with streptozotocin (NOD-sp./stz). In the first group, the transplants were rejected within 3 weeks. In the second and third groups, the transplants survived indefinitely. Alloxan, a drug similar to streptozotocin, did not have the same effect as streptozotocin. The ability of streptozotocin to prevent diabetes in young NOD mice was reversed by anti-CD8 antibody treatment but not by anti-CD4 treatment. Streptozotocin also made spleen cells from diabetic NOD mice less effective transferring diabetes. These results indicate that streptozotocin treatment both prevents and reverses the islet destructive autoimmunity in NOD mice. We postulate that the effects of streptozotocin treatment may be mediated in part by regulatory T cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Islet Transplantat Lab WH 541, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Koulmanda, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Islet Transplantat Lab WH 541, 55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [P01 DK53087] NR 44 TC 19 Z9 19 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2003 VL 134 IS 2 BP 210 EP 216 DI 10.1046/j.1365-2249.2003.02293.x PG 7 WC Immunology SC Immunology GA 734TW UT WOS:000186074900007 PM 14616779 ER PT J AU Supko, JG Eder, JP Ryan, DP Seiden, MV Lynch, TJ Amrein, PC Kufe, DW Clark, JW AF Supko, JG Eder, JP Ryan, DP Seiden, MV Lynch, TJ Amrein, PC Kufe, DW Clark, JW TI Phase I clinical trial and pharmacokinetic study of the spicamycin analog KRN5500 administered as a 1-hour intravenous infusion for five consecutive days to patients with refractory solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID PROMYELOCYTIC LEUKEMIA-CELLS; ANTITUMOR-ACTIVITY; DIFFERENTIATION INDUCERS; PHARMACOLOGY; COMPARTMENT; VALIDATION; PLASMA; LINES; HL-60; VITRO AB Purpose: The spicamycin analogue KRN5500 is a nucleoside-like antibiotic with broad spectrum activity against human solid tumor models. It appears to possess a novel mechanism of action directed against the endoplasmic reticulum and Golgi apparatus with effects on protein processing. A Phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetic behavior of KRN5500 given as a 1-h i.v. infusion for 5 consecutive days every 3 weeks. Experimental Design: Adult patients with refractory solid tumors, good performance status, and normal to near normal renal, hepatic, and hematological function were eligible for the study. At least three patients were evaluated at each dose level, and a modified Fibonacci algorithm was used for dose escalation. The MTD was based on the occurrence of severe toxicity during the first cycle of therapy. The plasma pharmacokinetics of KRN5500 was characterized during the first week of dosing. Results: Characteristics of the 26 patients entered into the study were as follows: 13 males and 13 females; median age, 54.5 years (range, 40-70 years); and Eastern Cooperative Oncology Group performance status 0-1. A majority had refractory colorectal carcinoma (17 of 26 patients) with at least two prior regimens of therapy. The dose of KRN5500 was escalated from 0.8 to 4.9 mg/m(2)/day in five dose levels, and the MTD was 2.9 mg/m(2)/day. All dose-limiting toxicities were nonhematological and included pulmonary toxicities, hyperglycemia, fatigue, hepatotoxicity, and ataxia, with one fatality due to interstitial pneumonitis. Clinically significant toxicities occurring in multiple patients that were not dose-limiting included nausea/vomiting, diarrhea, fatigue, neurological symptoms, hyperbilirubinemia, hyperglycemia, lymphopenia, and thrombocytopenia. There were no objective responses, although 3 of 17 evaluable patients exhibited disease stabilization for 5-6 cycles. The pharmacokinetics for the first dose of KRN5500 was biexponential and linear across all five dose levels. Mean values of pharmacokinetic parameters were as follows: total plasma clearance, 6.15 +/- 2.37 liters/h/m(2); apparent volume of distribution at steady state, 6.56 +/- 1.98 liters/m(2); biological half-life, 1.29 +/- 0.37 h; and mean residence time, 1.07 +/- 0.31 h. Clearance was significantly lower (P = 0.011) in the eight patients who were at least 65 years old (4.6 +/- 1.6 liters/h/m(2)) as compared with the 18 younger patients (7.1 +/- 2.3 liters/h/m(2)). Peak plasma concentrations of KRN5500 in the cohort receiving the MTD ranged from 350 to 400 ng/ml. Conclusions: The MTD of KRN5500, when given as a 1-h i.v. infusion for 5 consecutive days, was 2.9 mg/m(2)/day. The only suggestion of therapeutic activity observed in this study was disease stabilization in three patients with chemorefractory colorectal cancer. Administering KRN5500 as a continuous i.v. infusion with the objective of prolonging systemic exposure to potentially cytotoxic concentrations of the drug should be considered. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. RP Supko, JG (reprint author), Massachusetts Gen Hosp, Jackson Bldg,Room 1025,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [U01-CA-62490] NR 25 TC 9 Z9 9 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2003 VL 9 IS 14 BP 5178 EP 5186 PG 9 WC Oncology SC Oncology GA 743EA UT WOS:000186558400016 PM 14613997 ER PT J AU Bohning, DE Denslow, S Bohning, PA Walker, JA George, MS AF Bohning, DE Denslow, S Bohning, PA Walker, JA George, MS TI A TMS coil positioning/holding system for MR image-guided TMS interleaved with fMRI SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial magnetic stimulation; TMS; MR-guided positioning; interleaved TMS and fMRI ID TRANSCRANIAL MAGNETIC STIMULATION; BOLD-FMRI; CORTEX AB Objective: Transcranial magnetic stimulation (TMS) can be interleaved with fMRI to visualize regional brain activity in response to direct, non-invasive, cortical stimulation, making it a promising tool for studying brain function. A major practical difficulty is accurately positioning the TMS coil within the MRI scanner for stimulating a particular area of brain cortex. The objective of this work was to design and build a self-contained hardware/software system for MR-guided TMS coil positioning in interleaved TMS/fMRI studies. Methods: A compact, manually operated, articulated TMS coil positioner/holder with 6 calibrated degrees of freedom was developed for use inside a cylindrical RF head coil, along with a software package for transforming between MR image coordinates, MR scanner space coordinates, and positioner/holder settings. Results: Phantom calibration studies gave an accuracy for positioning within setups of dx = +/- 1.9 mm, dy = +/- 1.4 mm, dz = +/- 0.8 mm and a precision for multiple setups of dx = +/- 0.8 mm, dy = +/- 0.1 mm, dz = +/- 0.1 mm. Conclusions: This self-contained, integrated MR-guided TMS system for interleaved TMS/fMRI studies provides fast, accurate location of motor cortex stimulation sites traditionally located functionally, and a means of consistent, anatomy-based TMS coil positioning for stimulation of brain areas without overt response. (C) 2003 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 Med Univ S Carolina, Dept Radiol, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP Bohning, DE (reprint author), Med Univ S Carolina, Dept Radiol, Ctr Adv Imaging Res, 169 Ashley Ave, Charleston, SC 29425 USA. NR 15 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2003 VL 114 IS 11 BP 2210 EP 2219 DI 10.1016/S1388-2457(03)00232-3 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 743GH UT WOS:000186563700025 PM 14580621 ER PT J AU Sultan, PG Most, E Schule, S Li, G Rubash, HE AF Sultan, PG Most, E Schule, S Li, G Rubash, HE TI Optimizing flexion after total knee arthroplasty - Advances in prosthetic design SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the Knee-Society CY FEB, 2003 CL NEW ORLEANS, LOUISIANA SP Knee Soc ID POSTERIOR CRUCIATE LIGAMENT; FOLLOW-UP; TOTAL CONDYLAR; RHEUMATOID-ARTHRITIS; SURVIVORSHIP ANALYSIS; IMPLANT DESIGN; RANGE; MOTION; REPLACEMENT; POLYETHYLENE AB The clinical results with most modern total knee arthroplasty (TKA) designs are highly satisfactory regarding pain relief and improving walking ability. However, one problem that has not been addressed fully by most current designs is the ability to consistently achieve flexion greater than 120degrees. Although the human knee is capable of flexion of more than 150degrees, an analysis of the results of contemporary TKA reveals that on average, patients rarely flex beyond 120degrees. Key factors influencing range of flexion after TKA include preoperative knee motion, surgical technique, prosthetic design, and rehabilitation. The success of any total knee system may in part be linked to its ability to optimally restore normal kinematic function. Some arthroplasty designs currently are available that incorporate modifications aimed at improving range of flexion, but limited data currently are available on their function and potential advantages. Currently, an in vitro experimental model incorporating robotics is being used to investigate the kinematics of the native knee and various TKA designs at flexion angles beyond 120degrees. This robotic model in conjunction with clinical studies may provide an understanding of the limitations of contemporary knee designs regarding achieving higher degrees of knee flexion. This may lead to the refinement of existing designs and development of newer prostheses that may enhance the range of flexion that is achievable after TKA. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, BIDMC, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. RP Rubash, HE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, BIDMC, 55 Fruit St,Suite GRB 624, Boston, MA 02114 USA. NR 44 TC 52 Z9 62 U1 1 U2 10 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 NOV PY 2003 IS 416 BP 167 EP 173 DI 10.1097/01.blo.0000081937.75404.ed PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 741JF UT WOS:000186454400024 PM 14646757 ER PT J AU Most, E Li, G Schule, S Sultan, P Park, SE Zayontz, S Rubash, HE AF Most, E Li, G Schule, S Sultan, P Park, SE Zayontz, S Rubash, HE TI The kinematics of fixed- and mobile-bearing total knee arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the Knee-Society CY FEB, 2003 CL NEW ORLEANS, LOUISIANA SP Knee Soc ID FOLLOW-UP; IN-VITRO; MENISCAL BEARING; MUSCLE LOADS; PROSTHESIS; REPLACEMENT; DESIGN; MOTION; RANGE AB The success of any total knee arthroplasty (TKA) is influenced by a complex interaction between component geometry and the surrounding soft tissues. The objective of this study was to investigate posterior femoral translation and fibial rotation in a single design posterior-stabitized TKA offering fixed-and mobile-bearing tibial components. Specifically, we examined whether mobile-bearing TKA restores normal knee translation and rotation better than fixed-bearing TKA design. Eleven human knee specimens retrieved postmortem were tested using a robotic system. The translation and rotation of the intact and reconstructed knees were compared. The data indicate that for all knees, posterior femoral translation occurs along the passive path and under muscle loading conditions. Furthermore, increasing flexion angle corresponded with increased internal tibial rotation. Femoral translation and tibial rotation for fixed- and mobile-bearing posterior-stabilized TKAs were similar despite component design variations. However, both arthroplasties only partially restored intact knee translation and rotation. The data presented here may serve as an aid in the development of a rationale for additional improvement in surgical techniques and prosthesis design, so that normal knee function may be restored. C1 MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Orthopaed Biomech Lab, MGH,BIDMC, Boston, MA USA. RP Li, G (reprint author), Massachusetts Gen Hosp, Dept Bioengn, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. NR 33 TC 40 Z9 45 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2003 IS 416 BP 197 EP 207 DI 10.1097/01.blo.0000092999.90435.d1 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 741JF UT WOS:000186454400029 PM 14646762 ER PT J AU Goy, E Ganzini, L AF Goy, E Ganzini, L TI End-of-life care in geriatric psychiatry SO CLINICS IN GERIATRIC MEDICINE LA English DT Review ID ILL CANCER-PATIENTS; TERMINALLY-ILL; ALZHEIMERS-DISEASE; PALLIATIVE CARE; ADVANCED DEMENTIA; DEPRESSION SCALE; STAGE DEMENTIA; BEHAVIORAL DISTURBANCES; POSTOPERATIVE DELIRIUM; COGNITIVE IMPAIRMENT AB Depression, anxiety and delirium are relatively common during the final stages of terminal disease, and each can profoundly impact the quality of those last days for both patient and involved family. In this article the authors review the assessment and treatment of each syndrome in the context of palliative care for older adults. Treatment of mental disorders at the end of life warrants special consideration due to the need to balance the benefits of treatment against the potential burden of the intervention, especially those that might worsen quality of life. Dementia and the complications of depression and behavioral disturbance within dementia are also discussed. Finally, caregivers of dying patients are vulnerable to stress, depression, grief, and complicated bereavement. Interventions for caregivers who are debilitated by these states are briefly summarized. C1 Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. RP Goy, E (reprint author), Portland Vet Affairs Med Ctr, P3MHDC,POB 1034, Portland, OR 97207 USA. NR 113 TC 10 Z9 11 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD NOV PY 2003 VL 19 IS 4 BP 841 EP + DI 10.1016/S0749-0690(03)00029-6 PG 18 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 746KE UT WOS:000186744900010 PM 15024815 ER PT J AU Caballero, E AF Caballero, E TI Obesity, diabetes, and the metabolic syndrome: New challenges in antipsychotic drug therapy SO CNS SPECTRUMS LA English DT Article; Proceedings Paper CT 156th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 2003 CL SAN FRANCISCO, CALIFORNIA SP Amer Psychiat Assoc ID NUTRITION EXAMINATION SURVEY; IMPAIRED GLUCOSE-TOLERANCE; CORONARY-HEART-DISEASE; 3RD NATIONAL-HEALTH; BODY-MASS INDEX; WEIGHT-GAIN; US ADULTS; SCHIZOPHRENIA; INSULIN; PREVALENCE AB Obesity and diabetes continue to be national health epidemics. Greater than 50% of adults in the United States are overweight, and > 17 million people have diabetes-one third of whom are not diagnosed. Diabetes ranks number I in direct health care costs of any disease category. Patients who suffer from schizophrenia may be at twice the risk of developing diabetes compared with the general population. Some new antipsychotic agents are among several types of medications that may potentially impair glucose metabolism. For example, studies have shown that people treated with clozapine and olanzapine have developed elevated fasting serum insulin levels, suggestive of insulin resistance. Insulin resistance may be a result of irregularities in the insulin action sequence and it may occur long before overt diabetes. The further study of the effects of medications on glucose metabolism and their mechanisms, therefore, is essential to developing better treatment regimens that minimize insulin resistance and avoid associated health risks such as obesity and diabetes. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Caballero, E (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 26 TC 12 Z9 13 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD NOV PY 2003 VL 8 IS 11 SU 2 BP 19 EP 22 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 754RJ UT WOS:000187344900005 PM 14978454 ER PT J AU Akita, H Akamatsu, H Matsunaga, K AF Akita, H Akamatsu, H Matsunaga, K TI Allergic contact dermatitis due to phenylephrine hydrochloride, with an unusual patch test reaction SO CONTACT DERMATITIS LA English DT Article DE long-lasting allergic patch test reactions; patch testing technique; phenylephrine hydrochloride; scratch-patch test; unusual patch test reaction ID EYEDROPS AB 2-day (2-D) closed patch tests are often used in daily clinical practice and useful for evaluating the cause of allergic contact dermatitis. However, even when 2-D closed patch tests at appropriate concentrations are performed for suspected allergic contact dermatitis based on clinical findings, positive reactions are not always obtained. Therefore, although the use of the allergen again induces similar symptoms, a definite diagnosis cannot be made in some cases. We report a case of allergic contact dermatitis due to phenylephrine hydrochloride in eyedrops, with an unusual patch test reaction. Although the results of the routine 2-D closed patch test were negative, a definite diagnosis could be made by closed scratch-patch test. In addition, long-lasting allergic patch test reactions were observed at the positive scratch-patch test site for about 3 months. We speculated that these unusual results on patch testing in our case were associated with the degree of percutaneous absorption of causative agents. Therefore, even when 2-D closed patch tests are negative, scratch-patch tests may be indicated for patients in whom clinical symptoms continue strongly to suggest contact dermatitis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Fujita Hlth Univ, Sch Med, Dept Dermatol, Toyoake, Aichi 47011, Japan. RP Akita, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 55 Fruit St,BHX 630, Boston, MA 02114 USA. EM hakita@partners.org NR 10 TC 15 Z9 15 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-1873 J9 CONTACT DERMATITIS JI Contact Dermatitis PD NOV PY 2003 VL 49 IS 5 BP 232 EP 235 DI 10.1111/j.0105-1873.2003.0250.x PG 4 WC Allergy; Dermatology SC Allergy; Dermatology GA 776VL UT WOS:000189140000002 PM 14996044 ER PT J CA ARDS Clinical Trials Network Natl Heart Lung Blood Inst Natl Inst Hlth TI Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 97th International Conference of the American-Thoracic-Society CY MAY 18-23, 2001 CL SAN FRANCISCO, CA SP Amer Thorac Soc DE respiratory distress syndrome; adult; ventilators; mechanical; atelectasis; acute lung injury ID TIDAL VOLUME; GAS-EXCHANGE; MECHANICAL VENTILATION; PROTECTIVE-VENTILATION; ALVEOLAR RECRUITMENT; INFLATION; PULMONARY; SURFACTANT; STRATEGY; FAILURE C1 Denver Hlth Med Ctr, Denver, CO USA. Denver VA Med Ctr, Denver, CO USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Johns Hopkins Univ, Bayview Med Ctr, Baltimore, MD 21218 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. LDS Hosp, Salt Lake City, UT USA. McKay Dee Hosp, Ogden, UT USA. Metrohlth Med Ctr, Cleveland, OH 44109 USA. San Francisco Gen Hosp, Med Ctr, San Francisco, CA 94110 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Utah Hosp, Salt Lake City, UT 84112 USA. Washington Univ, Harborview Med Ctr, St Louis, MO 63130 USA. Utah Valley Reg Med Ctr, Provo, UT USA. Vanderbilt Univ, Nashville, TN USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Coordinating Ctr, Cambridge, MA 02138 USA. NHLBI, ARDS Clin Trials Network, NIH, Bethesda, MD USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 33 TC 1 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2003 VL 31 IS 11 BP 2592 EP 2597 DI 10.1097/01.CCM.0000090001.91640.45 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 744JT UT WOS:000186626000005 ER PT J AU Huh, J Wall, MJ Soltero, ER AF Huh, J Wall, MJ Soltero, ER TI Treatment of combined coronary and carotid artery disease SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE coronary; carotid; coronary artery bypass; carotid endarterectomy ID OFF-PUMP; MYOCARDIAL REVASCULARIZATION; CARDIOPULMONARY BYPASS; CONCOMITANT CORONARY; CARDIAC-SURGERY; RISK-FACTORS; FOLLOW-UP; ENDARTERECTOMY; STROKE; STENOSIS AB Despite a large volume of data present in the literature, the treatment indications and surgical options remain controversial. We currently advocate treatment of symptomatic territory first in favor of staged procedures and reserve combined procedures for patients with critical stenosis or symptoms in both territories. C1 Ben Taub Gen Hosp, Div Cardiothorac Surg, Houston Vet Affairs Med Ctr, Baylor Coll Med, Houston, TX 77030 USA. RP Huh, J (reprint author), Houston Vet Affairs Med Ctr 112, 2002 Holcombe Blvd, Houston, TX 77401 USA. EM joseph.huh@med.va.gov NR 51 TC 31 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD NOV PY 2003 VL 18 IS 6 BP 447 EP 453 DI 10.1097/00001573-200311000-00005 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 864IE UT WOS:000224626400005 PM 14597885 ER PT J AU Bi, LC Kaunitz, JD AF Bi, LC Kaunitz, JD TI Gastroduodenal mucosal defense: an integrated protective response SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE stomach; injury; Helicobacter pylori; nonsteroidal anti-inflammatory drugs; trefoil peptides; adrenomedullin ID HELICOBACTER-PYLORI INFECTION; TRANSMEMBRANE CONDUCTANCE REGULATOR; GASTRIC-ULCER; ACID-SECRETION; DUODENAL-ULCER; RAT; ADRENOMEDULLIN; STOMACH; CELLS; MICE AB Purpose of review The remarkable resistance of the mucosal lining the upper gastrointestinal tract to concentrated gastric acid remains one of the biggest unsolved mysteries of upper gastrointestinal physiology. Even with the discovery of the involvement of Helicobacter pylori in gastroduodenal injury, the mechanism by which the organism causes injury remains unresolved. In the past year, there have been striking findings regarding trefoil peptides, the protective effect of regulatory peptides such as adrenomedullin, and the influence of H. pylori on the junctions that join the epithelial cells. Recent findings Trefoil peptide-2-deficient mice were more susceptible to gastric injury from nonsteroidal anti-inflammatory agents, confirming that trefoil peptides increased the barrier properties of the pre-epithelial mucus gel. With regard to H. pylori, the gastric mucosa of mice deficient in the tyrosine phosphatase receptor type Z were not damaged by H. pylori vacuolating cytotoxin. Proton pump inhibition appears to be equally or more effective in upper gastrointestinal mucosal protection compared with other interventions such as exogenous prostaglandins or H. pylori eradication. Summary Peptic ulcer disease, although declining in prevalence, appears to be increasing in virulence, perhaps because of the overall aging of the population and improved intensive care unit care. Although H. pylori and nonsteroidal anti-inflammatory drugs have been identified as key pro-ulcerogenic factors, many ulcers may also result from a deficiency of other, unknown host protective factors. A more detailed understanding of the host factors involved in mucosal protection will thus help identify novel therapeutic targets aimed at the prevention and treatment of upper gastrointestinal mucosal injury. C1 W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Irvine, Irvine, CA USA. Long Beach VA Med Ctr, Long Beach, CA USA. Univ Calif Los Angeles, Sch Med, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Los Angeles, CA 90024 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Bldg 114,Suite 217, Los Angeles, CA 90073 USA. NR 49 TC 7 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2003 VL 19 IS 6 BP 526 EP 532 DI 10.1097/00001574-200311000-00003 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 735VM UT WOS:000186135300003 PM 15703600 ER PT J AU Walker, WA AF Walker, WA TI Immunology SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Div Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mucosal Immun Lab, Boston, MA 02114 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, 114 16th St,114-3503, Charlestown, MA 02129 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2003 VL 19 IS 6 BP 557 EP 558 DI 10.1097/00001574-200311000-00007 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 735VM UT WOS:000186135300007 ER PT J AU Cherayil, BJ AF Cherayil, BJ TI How not to get bugged by bugs: mechanisms of cellular tolerance to microorganisms SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE macrophage; endotoxin tolerance; inflammation; intestine ID RECEPTOR-ASSOCIATED KINASE; NF-KAPPA-B; INTESTINAL EPITHELIAL-CELLS; INDUCED MACROPHAGE ACTIVATION; TNF-ALPHA PRODUCTION; TOLL-LIKE RECEPTOR-2; ENDOTOXIN TOLERANCE; CUTTING EDGE; MURINE MACROPHAGES; SIGNALING PATHWAYS AB Purpose of review Advances in the characterization of the receptors and signaling pathways involved in the response to infection have led to a more detailed understanding of cellular tolerance to endotoxin and other microbial components. This review summarizes recent progress in the field, particularly in relation to the molecular mechanisms that underlie the development of tolerance to microorganisms. Recent findings The identification of Toll-like receptors as major sensors of microbial molecules has led to numerous studies of their function in tolerant cells. Decreased Toll-like receptor expression, altered interactions between the Toll-like receptors and intracellular signal transducers, and decreased expression or activity of downstream signaling molecules have all been implicated. Upregulation of specific proteins that inhibit Toll-like receptor signaling has also been described. Apart from these general mechanisms, special features of the intestinal microenvironment and its resident cells also contribute to making the gut hyporesponsive to microorganisms. Summary The application of gene knockout technology has highlighted the importance of macrophage tolerance in regulating innate immunity to microbial infection. Such studies have indicated that the failure of tolerance can lead to exaggerated inflammatory responses to intestinal bacteria, raising the possibility that defects in tolerance may be linked to conditions such as inflammatory bowel disease. Further characterization of this link will help in elucidating the pathogenesis of such conditions and in devising new approaches to treatment. C1 Massachusetts Gen Hosp, Div Pediat Gastroenterol, Mucosal Immun Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Cherayil, BJ (reprint author), Pediat Gastroenterol Unit, Room 3400,MGH East,Bldg 114,16th St, Boston, MA 02129 USA. NR 53 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2003 VL 19 IS 6 BP 572 EP 577 DI 10.1097/00001574-200311000-00010 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 735VM UT WOS:000186135300010 PM 15703607 ER PT J AU Antin, JH AF Antin, JH TI Stem cell transplantation-harnessing of graft-versus-malignancy SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE stem cells; graft-versus-malignancy effect; allogeneic transplantation ID BONE-MARROW-TRANSPLANTATION; NONMYELOABLATIVE CONDITIONING REGIMEN; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; MULTIPLE-MYELOMA; HEMATOLOGIC MALIGNANCIES; PREPARATIVE REGIMENS; UNRELATED DONORS; HODGKINS-DISEASE; EUROPEAN GROUP AB Purpose of review Allogeneic transplantation can cure a number of hematologic malignancies; however, the cost in morbidity and mortality is high. Much of the toxicity is a direct consequence of the intensity of the conditioning regimen. It has gradually been recognized that the conditioning regimen is important but not critical for the success of transplantation, particularly in the less aggressive hematologic malignancies. The graft-versus-malignancy effect, that is, the recognition of residual cancer cells by the T cells of the donor, is a critical component of the transplantation process. Recent findings This effect has been emphasized over high-dose therapy by using less intensive, and therefore less toxic conditioning regimens, thus allowing the graft-versus-malignancy effect to predominate. Reduced-intensity conditioning regimens have allowed the application of transplantation to older patients and to patients with underlying medical problems that preclude full-dose transplantation. Summary Although the long-term results of this type of approach have not yet been defined, it appears to be effective in diseases such as chronic myelogenous leukemia, chronic lymphocytic leukemia, and low-grade lymphomas that are not intrinsically very aggressive. Although the therapy appears to be valuable, concerns about delayed immune reconstitution and graft-versus-host disease remain. C1 Harvard Univ, Sch Med,Stem Cell Transplantat Program, Dana Farber Canc Inst,Dept Med, Brigham & Womens Hosp,Div Med Oncol & Hematol, Boston, MA 02115 USA. RP Antin, JH (reprint author), Harvard Univ, Sch Med,Stem Cell Transplantat Program, Dana Farber Canc Inst,Dept Med, Brigham & Womens Hosp,Div Med Oncol & Hematol, 44 Binney St, Boston, MA 02115 USA. NR 44 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD NOV PY 2003 VL 10 IS 6 BP 440 EP 444 DI 10.1097/00062752-200311000-00008 PG 5 WC Hematology SC Hematology GA 736CX UT WOS:000186154100008 PM 14564175 ER PT J AU Wadleigh, M Ho, V Momtaz, P Richardson, P AF Wadleigh, M Ho, V Momtaz, P Richardson, P TI Hepatic veno-occlusive disease: pathogenesis, diagnosis and treatment SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE chemotherapy; high dose endothelial injury; risk factors; stem cell transplant; hematopoietic; veno-occlusive disease; hepatic ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; TISSUE-PLASMINOGEN-ACTIVATOR; VENO-OCCLUSIVE DISEASE; HIGH-RISK POPULATION; MULTISYSTEM ORGAN FAILURE; MOLECULAR-WEIGHT HEPARIN; HIGH-DOSE CHEMOTHERAPY; RANDOMIZED-TRIAL; PHASE-II AB Hepatic veno-occlusive disease (VOD) is one of the most serious complications following hematopoietic stem cell transplantation (SCT) and is associated with a very high mortality in its severe form. This review outlines the pathogenesis and clinical features of VOD, with an emphasis on endothelial cell injury and risk factors. The current status and future directions of research for both prophylaxis and treatment are also discussed. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Dept Adult Oncol, Boston, MA 02115 USA. RP Richardson, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 148 TC 68 Z9 74 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD NOV PY 2003 VL 10 IS 6 BP 451 EP 462 DI 10.1097/00062752-200311000-00010 PG 12 WC Hematology SC Hematology GA 736CX UT WOS:000186154100010 PM 14564177 ER PT J AU Ruvinsky, I Ruvkun, G AF Ruvinsky, I Ruvkun, G TI Functional tests of enhancer conservation between distantly related species SO DEVELOPMENT LA English DT Article DE evolution; enhancer; C. elegans; C. briggsae; D. melanogaster; co-evolution ID CIS-REGULATORY SEQUENCES; CAENORHABDITIS-ELEGANS; C-ELEGANS; NERVOUS-SYSTEM; DROSOPHILA-MELANOGASTER; EVOLUTIONARY CONSERVATION; PHARYNGEAL DEVELOPMENT; SPECIFICATION GENE; HOX PROTEIN; EXPRESSION AB Expression patterns of orthologous genes are often conserved, even between distantly related organisms, suggesting that once established, developmental programs can be stably maintained over long periods of evolutionary time. Because many orthologous transcription factors are also functionally conserved, one possible model to account for homologous gene expression patterns, is conservation of specific binding sites within cis-regulatory elements of orthologous genes. If this model is correct, a cis-regulatory element from one organism would be expected to function in a distantly related organism. To test this hypothesis, we fused the green fluorescent protein gene to neuronal and muscular enhancer elements from a variety of Drosophila melanogaster genes, and tested whether these would activate expression in the homologous cell types in Caenorhabditis elegans. Regulatory elements from several genes directed appropriate expression in homologous tissue types, suggesting conservation of regulatory sites. However, enhancers of most Drosophila genes tested were not properly recognized in C elegans, implying that over this evolutionary distance enough changes occurred in cis-regulatory sequences and/or transcription factors to prevent proper recognition of heterospecific enhancers. Comparisons of enhancer elements of orthologous genes between C. elegans and C. briggsae revealed extensive conservation, as well as specific instances of functional divergence. Our results indicate that functional changes in cis-regulatory sequences accumulate on timescales much shorter than the divergence of arthropods and nematodes, and that mechanisms other than conservation of individual binding sites within enhancer elements are responsible for the conservation of expression patterns of homologous genes between distantly related species. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Biol Mol, Wellman 8, Boston, MA 02114 USA. NR 68 TC 57 Z9 66 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 2003 VL 130 IS 21 BP 5133 EP 5142 DI 10.1242/dev.00711 PG 10 WC Developmental Biology SC Developmental Biology GA 755JK UT WOS:000187399600008 PM 12944426 ER PT J AU Kim, JYH Nelson, AL Algon, SA Graves, O Sturla, LM Goumnerova, LC Rowitch, DH Segal, RA Pomeroy, SL AF Kim, JYH Nelson, AL Algon, SA Graves, O Sturla, LM Goumnerova, LC Rowitch, DH Segal, RA Pomeroy, SL TI Medulloblastoma tumorigenesis diverges from cerebellar granule cell differentiation in patched heterozygous mice SO DEVELOPMENTAL BIOLOGY LA English DT Article DE apoptosis; cerebellum; granule cell; medulloblastoma; mouse; patched; proliferation; trkC ID CENTRAL-NERVOUS-SYSTEM; PRIMITIVE NEUROECTODERMAL TUMORS; SONIC-HEDGEHOG; HUMAN HOMOLOG; PRECURSOR PROLIFERATION; CARCINOMA SYNDROME; NEURON PRECURSORS; STAINING METHODS; RECEPTOR TRKC; EXPRESSION AB Medulloblastoma is a cerebellar tumor that can arise through aberrant activation of Sonic hedgehog (Shh) signaling, which normally regulates cerebellar granule cell proliferation. Mutations of the Shh receptor PATCHED (PTCH) are associated with medulloblastomas, which have not been found to have loss of PTCH heterozygosity. We address whether patched (Ptc) heterozygosity fundamentally alters granule cell differentiation and contributes to tumorigenesis by increasing proliferation and/or decreasing apoptosis in Ptc+/- mice. Our data show that postnatal Ptc+/- mouse granule cell precursor growth is not globally altered. However, many older Ptc+/- mice display abnormal cerebellar regions containing persistently proliferating granule cell precursors. Since fewer Ptc+/- mice form medulloblastomas, these granule cell rests represent a developmentally disrupted, but uncommitted stage of tumorigenesis. Although Ptc+/- mouse medulloblastomas express neurodevelopmental genes, they diverge from granule cell differentiation in their discordant coexpression of postmitotic markers despite their ongoing growth. Like human medulloblastomas, mouse tumors with reduced levels of the neurotrophin-3 receptor, trkC/Ntrk3, display decreased apoptosis in vivo, illustrating the role of TrkC in regulating tumor cell survival. These results indicate that Ptc heterozygosity contributes to tumorigenesis by predisposing a subset of granule cell precursors to the formation of proliferative rests and subsequent dysregulation of developmental gene expression. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci,Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci,Dept Neurosurg, Boston, MA 02115 USA. RP Pomeroy, SL (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci,Dept Neurol, Boston, MA 02115 USA. FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS35701, NS043517-01, NS37757] NR 64 TC 57 Z9 59 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 1 PY 2003 VL 263 IS 1 BP 50 EP 66 DI 10.1016/S0012-1606(03)00434-2 PG 17 WC Developmental Biology SC Developmental Biology GA 737RG UT WOS:000186245100005 PM 14568546 ER PT J AU Wrobel, JS Charns, MP Diehr, P Robbins, JM Reiber, GE Bonacker, KM Haas, LB Pogach, L AF Wrobel, JS Charns, MP Diehr, P Robbins, JM Reiber, GE Bonacker, KM Haas, LB Pogach, L TI The relationship between provider coordination and diabetes-related foot outcomes SO DIABETES CARE LA English DT Article ID LOWER-EXTREMITY ULCERS; SURGICAL SERVICES; CARE; QUALITY; ASSOCIATION; UNITS AB OBJECTIVE - To investigate the relationship between provider coordination and amputations in patients with diabetes. RESEARCH DESIGN AND METHODS- The study design was a cross-sectional descriptive study of process and outcomes for diabetes-related foot care at 10 Department of Veterans Affairs (VA) medical centers representing different geographic regions, population densities, patient populations, and amputation rates. The subjects included all providers of diabetes foot care and a random sample of primary care providers at each medical center. The main outcome measures were the Foot Systems Assessment Tool (FootSAT), nontraumatic lower extremity amputation rates, and investigators' ordinal ranking of site effectiveness based on site visits. RESULTS - The survey response rate was 48%. Scale reliability, as measured by Cronach's alpha, ranged from 0.73 to 0.93. The scale scores for programming coordination ( medical record, policies, reminders, protocols, and educational seminars) and feedback coordination (i.e., discharge planning, quality of care meetings, and curbside consultations) were negatively associated with amputation rates, suggesting centers with higher levels of coordination had lower amputation rates. Statistically significant associations were found for programming coordination with minor amputations (P = 0.02) and total amputations (P = 0.04). CONCLUSIONS - The FootSAT demonstrated a stronger association with amputation rates than site visit rankings. Among these 10 VA facilities, those with higher levels of programming and feedback coordination had significantly lower amputation rates. C1 VA Med & Reg Off Ctr, Dept Vet Affairs, White River Jct, VT USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. Boston Univ, Sch Publ Hlth, VA Management Decis & Res Ctr, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Program Hlth Policy & Management, Boston, MA 02215 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Cleveland VA Med Ctr, Dept Vet Affairs, Cleveland, OH USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv & Res & Dev, Dept Vet Affairs, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Dept Vet Affairs, Seattle, WA USA. VA New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. RP Wrobel, JS (reprint author), VA White River Junct, Surg Serv, 112E, White River Jct, VT 05009 USA. NR 27 TC 23 Z9 23 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2003 VL 26 IS 11 BP 3042 EP 3047 DI 10.2337/diacare.26.11.3042 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738CL UT WOS:000186269100012 PM 14578237 ER PT J AU Polonsky, WH Earles, J Smith, S Pease, DJ Macmillan, M Christensen, R Taylor, T Dickert, J Jackson, RA AF Polonsky, WH Earles, J Smith, S Pease, DJ Macmillan, M Christensen, R Taylor, T Dickert, J Jackson, RA TI Integrating medical management with diabetes self-management training - A randomized control trial of the Diabetes Outpatient Intensive Treatment program SO DIABETES CARE LA English DT Article ID MICROVASCULAR COMPLICATIONS; BLOOD-PRESSURE; MELLITUS; THERAPY; RISK AB OBJECTIVE - This study evaluated, the Diabetes Outpatient Intensive Treatment (DOIT) program, a multiday group education and skills training experience combined with daily medical. management, followed by case management over 6 months. Using a randomized control design, the study explored how DOIT affected glycemic control and self-care behaviors over a short term. The impact of two additional factors on clinical outcomes were also examined (frequency of case management contacts and whether or not insulin was started during the program). RESEARCH DESIGN AND METHODS - Patients with type I and type 2 diabetes in poor glycemic control (Alc >8.5%) were randomly assigned to DOIT or a second condition, entitled EDUPOST, which was standard diabetes care with the addition of quarterly educational mailings. A total of 167 patients (78 EDUPOST, 89 DOIT). completed all baseline measures, including Alc and a questionnaire assessing diabetes-related self-care behaviors. At 6 months, 117 patients (52 EDUPOST, 65 DOIT) returned to complete a follow-up Alc and the identical self-care questionnaire. RESULTS- At follow-up, DOIT evidenced a significantly greater drop in Alc than EDUPOST. DOIT patients also reported significantly more frequent blood glucose monitoring and greater attention to carbohydrate and fat contents (ACFC) of food compared with EDUPOST patients. An increase in ACFC over the 6-month period was associated with improved glycemic control among DOIT patients. Also, the frequency of nurse case manager follow-up contacts was positively linked to better Alc outcomes. The addition of insulin did not appear to be a significant contributor to glycemic change. CONCLUSIONS - DOIT appears to be effective in promoting better diabetes care and positively influencing glycemia and diabetes-related self-care behaviors. However, it demands significant time, commitment, and careful coordination with many health care professionals. The role of the nurse case manager in providing ongoing follow-up contact seems important. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Tripler Army Med Ctr, Honolulu, HI 96859 USA. Pearl Harbor Naval Med Clin, Honolulu, HI USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jackson, RA (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 11 TC 73 Z9 73 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2003 VL 26 IS 11 BP 3048 EP 3053 DI 10.2337/diacare.26.11.3048 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738CL UT WOS:000186269100013 PM 14578238 ER PT J AU Laffel, LMB Connell, A Vangsness, L Goebel-Fabbri, A Mansfield, A Anderson, BJ AF Laffel, LMB Connell, A Vangsness, L Goebel-Fabbri, A Mansfield, A Anderson, BJ TI General quality of life in youth with type 1 diabetes - Relationship to patient management and diabetes-specific family conflict SO DIABETES CARE LA English DT Article; Proceedings Paper CT 60th Scientific Sessions of the American-Diabetes-Association CY JUN 09-13, 2000 CL San Antonio, TX SP Amer Diabet Assoc ID GLYCEMIC CONTROL; CHILDREN; ADOLESCENTS; INTERVENTION; MELLITUS; ADJUSTMENT; TEAMWORK; HEALTH; IMPACT; RISK AB OBJECTIVE - To evaluate self-report and parent proxy report of child/teen general quality of life in youth with type 1 diabetes, compare their responses with those of a general pediatric population, and identify relationships between diabetes management, diabetes-related family behavior, and diabetes-specific family conflict with quality of life in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS - Study participants included 100 children, 8-17 years of age (12.1 +/- 2.3), with type 1 diabetes for 0.5-6 years (2.7 +/- 1.6). Each child and a parent completed the Pediatric Quality of Life Inventory (PedsQL), completed the Diabetes Family Conflict Scale, and provided data on parent involvement in diabetes management. An independent measure of adherence to treatment assessed by the patient's clinician and a measure of glycemic control (HbA(1c)) were also collected. RESULTS - PedsQL responses from youth with type 1 diabetes were stable over 1 year and similar to norms from a healthy standardization sample for all three scales of the PedsQL: total, physical, and psychosocial quality of life. After controlling for age, duration of diabetes, sex, HbA(1c), and family involvement, child report of diabetes-specific family conflict (P < 0.01) was the only significant predictor of child report of quality of life (model R-2 = 0.21, P < 0.02). CONCLUSIONS - Youth with type 1 diabetes report remarkably similar quality of life to a nondiabetic youth population. Greater endorsement of diabetes-specific family conflict predicted diminished quality of life for the child. As treatment programs focus on intensifying glycemic control in youth with type 1 diabetes, interventions should include efforts to reduce diabetes-specific family conflict in order to preserve the child's overall quality of life. C1 Harvard Univ, Pediat & Adolescent Unit, Sch Med,Behav Res & Mental Hlth Sect, Genet & Epidemiol Sect,Joslin Diabet Ctr,, Boston, MA 02215 USA. RP Laffel, LMB (reprint author), Harvard Univ, Pediat & Adolescent Unit, Sch Med,Behav Res & Mental Hlth Sect, Genet & Epidemiol Sect,Joslin Diabet Ctr,, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [DK-46887, R01 DK046887] NR 32 TC 112 Z9 114 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2003 VL 26 IS 11 BP 3067 EP 3073 DI 10.2337/diacare.26.11.3067 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738CL UT WOS:000186269100016 PM 14578241 ER PT J AU Malecki, MT Frey, J Klupa, T Skupien, J Walus, M Mlynarski, W Sieradzki, J AF Malecki, MT Frey, J Klupa, T Skupien, J Walus, M Mlynarski, W Sieradzki, J TI The Pro12Ala polymorphism of PPAR gamma 2 gene and susceptibility to type 2 diabetes mellitus in a Polish population SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE type 2 diabetes mellitus; PPAR gamma gene; genetic susceptibility ID PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA-2; PPAR-GAMMA-GENE; INSULIN SENSITIVITY; ASSOCIATION; OBESITY; SUBSTITUTION; MUTATION; CALPAIN-10; RESISTANCE; ADIPOSITY AB Introduction: It has recently been shown that polymorphisms of some genes might influence the genetic susceptibility to complex, multifactorial forms of type 2 diabetes mellitus (T2DM). One of those genes is peroxisome proliferator activated receptor gamma (PPARgamma). The PPARgamma gene product is a nuclear hormone receptor that regulates adipogenesis and is a target for thiazolidinediones, medications enhancing sensitivity to insulin. The Pro12Ala amino acid variant of the PPARgamma2 isoform is associated with T2DM in several populations. Aims: (1) To determine the allele and genotype frequency of the Pro12Ala PPARgamma2 amino acid variant in a Polish population; (2) To search for the association of the Pro12Ala polymorphism with T2DM in the examined population. Methods: We included 644 individuals in this study: 366 T2DM patients with age of diagnosis greater than 35 years and 278 non-diabetic control subjects. The fragment of the PPARgamma2 gene which contains the examined amino acid variant was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined based on electrophoresis of the DNA digestion products by the specific restriction enzyme BshI. Differences in distribution between the groups were examined by chi(2) test. Results: The frequency of Pro/Ala alleles was similar in T2DM patients and in the control subjects (83.5%/16.5% vs. 84.5%/15.5%, respectively, P = 0.607). Similarly, there was no difference between the groups when we analysed the genotype distribution. Stratification analyses based on age of diagnosis, body mass index (BMI), and family history of T2DM were performed. The Pro/Ala and Ala/Ala genotypes tended to be more frequent in T2DM cases with age of diagnosis > 50 years than in controls (36.2% vs. 27.3%, P = 0.046). This difference was not significant after Sheffe correction for multiple comparisons. The other stratification analyses did not show any difference between the groups. Conclusion: The frequency of the Pro12Ala PPARgamma2 polymorphism in the Polish population studied is similar to that in other Caucasian populations. In the case-control study, we were not able to confirm earlier reports that the Pro allele conferred an increased risk for development of T2DM. Moreover, the results of the stratified analysis suggest an opposite trend in late onset T2DM. (C) 2003 Published by Elsevier Ireland Ltd. C1 Jagiellonian Univ, Coll Med, Dept Metab Dis, PL-31501 Krakow, Poland. Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. RP Malecki, MT (reprint author), Jagiellonian Univ, Coll Med, Dept Metab Dis, 15 Kopernika St, PL-31501 Krakow, Poland. FU NCI NIH HHS [CA 1 R03 TW01351-01] NR 36 TC 24 Z9 24 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD NOV PY 2003 VL 62 IS 2 BP 105 EP 111 DI 10.1016/S0168-8227(03)00164-5 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 742QQ UT WOS:000186529900005 PM 14581147 ER PT J AU Maggard, MA Beanes, SR Ko, CY AF Maggard, MA Beanes, SR Ko, CY TI Anal canal cancer - A population-based reappraisal SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY JUN 03-09, 2002 CL CHICAGO, ILLINOIS SP Amer Soc Colon & Rectal Surg DE anal canal cancer; incidence rates; survival; racial/ethnic disparities ID RADIATION-THERAPY; RANDOMIZED TRIAL; CERVICAL-CANCER; CARCINOMA; CHEMOTHERAPY; CHEMORADIATION; RADIOTHERAPY; MITOMYCIN; OUTCOMES; PROGRAM AB PURPOSE: This study was designed to obtain an updated population-based perspective on anal canal cancer incidence rates, demographics, and outcomes using a nationwide database. Eight-five percent of all carcinomas of the anus are anal canal cancers, and previous studies suggest that incidence rates may be rising. Although the most successful treatment for anal canal cancer has been chemoradiation, little information at the population-level exists regarding demographics, treatment, and survival. METHODS: All patients diagnosed with anal canal cancer from 1973 to 1998 in the Surveillance Epidemiology and End Results cancer registry were analyzed. Data regarding demographics, cancer characteristics, treatment, and survival were assessed. Univariate and multivariate survival analyses were performed. RESULTS: A total of 4,841 patients were studied (mean age was 61 years; 62 percent female). Female patients were significantly older than male patients (65 vs. 58 years; P < 0.0001). There was a yearly increase in incidence of anal canal cancers (from 1973-1998). Disease prevalence by stage was localized (53 percent), regional (38 percent), and distant (9 percent). Racial/stage differences were seen, because black patients had less localized disease than white patients (46 vs. 53 percent; P < 0.01). Overall five-year survival for the entire cohort was 53 percent, and cancer-specific survival was 84 percent. Survival improved per decade (based on year of diagnosis). Significant survival differences in race were noted, but were less when the receipt of treatment was considered. CONCLUSION: Although most anal canal cancer reviews are single institutional series, this study was performed with population-based data. The incidence of anal canal cancer is increasing, and overall survival rates are improving. Important disparities in care were identified, which need to be addressed. C1 Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Robert Wood Johnson VA Clin Scholars Program, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm, Dept Surg, Los Angeles, CA USA. RP Maggard, MA (reprint author), Univ Calif Los Angeles, Sch Med, Dept Surg, 10833 Le Conte Ave,CHS Room 72-215, Los Angeles, CA 90095 USA. NR 28 TC 36 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD NOV PY 2003 VL 46 IS 11 BP 1517 EP 1523 DI 10.1097/01.DCR.0000093722.63657.B4 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 743FF UT WOS:000186561200012 PM 14605572 ER PT J AU Worthington, JJ Peters, PM AF Worthington, JJ Peters, PM TI Treatment of antidepressant-induced sexual dysfunction SO DRUGS OF TODAY LA English DT Review ID SEROTONIN REUPTAKE INHIBITOR; SUSTAINED-RELEASE BUPROPION; MAJOR DEPRESSIVE DISORDER; DOUBLE-BLIND; ADVERSE INTERACTION; INDUCED ANORGASMIA; FLUOXETINE; SERTRALINE; OUTPATIENTS; PAROXETINE AB This article reviews the prevalence of antidepressant-induced sexual dysfunction and the strategies available for managing sexual adverse events. A high incidence of sexual dysfunction has been observed in patients treated with antidepressants. In particular, it has been reported in more than half of the patients treated with selective serotonin reuptake inhibitors. There are various pharmacotherapeutic strategies that can lead to reversal of sexual dysfunction. This article will review clinical studies on pharmacotherapeutic agents used to treat antidepressant-induced sexual dysfunction, as well as agents used to treat depression with a favorable sexual side-effect profile. Because sexual dysfunction can lead to treatment. noncompliance and depression relapse, this is an issue that should be addressed by clinicians at initiation and throughout the course of treatment. (C) 2003 Prous Science. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Worthington, JJ (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 815, Boston, MA 02114 USA. EM jworthington@partners.org NR 49 TC 13 Z9 13 U1 1 U2 4 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0025-7656 J9 DRUGS TODAY JI Drugs Today PD NOV PY 2003 VL 39 IS 11 BP 887 EP 896 DI 10.1358/dot.2003.39.11.799466 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 779BJ UT WOS:000189275500006 PM 14702134 ER PT J AU Scott, NS King, ME McQuillan, B Shariff, S Hung, JW Januzzi, JL Palacios, IF Picard, MH AF Scott, NS King, ME McQuillan, B Shariff, S Hung, JW Januzzi, JL Palacios, IF Picard, MH TI Effect of atrial septal mobility on transcatheter closure of interatrial communications SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE atrial septal defect; patent foramen ovale; transcatheter closure device; echocardiography ID BUTTONED DEVICE; ECHOCARDIOGRAPHIC PREDICTORS; DEFECT; SUCCESS AB Background: 7 Transcatheter techniques have evolved as alternatives to surgical closure of interatrial communications due to its less invasive nature and low morbidity. The technique may be limited by the inability to deploy the device and, thus, may be complicated by significant residual shunting. Mobile or redundant septal tissue has been implicated as a possible cause of unsuccessful closure. Methods: To determine if atrial septal hypermobility precludes successful transcatheter device closure of interatrial communications, 69 patients (mean age 46.4 +/- 17.5years [male:female ratio 34:35]) with periprocedural transesophageal echocardiograms were reviewed. Septal excursion was defined as the maximal transit of the interatrial septum between either side of the plane connecting the superior and inferior attachment points. Unsuccessful closure was defined as subsequent cardiac surgery to close the defect, inability to deploy the device, recurrent attempts at closure, device malalignment, residual shunting greater than mild in degree on follow-up transthoracic study, and procedural complications. Results: Reasons for closure were the following: embolic events (n = 48); platypnea/orthodeoxia (n = 15); atrial septal defect with right ventricular dilatation and paroxysmal atrial tachycardia (n = 2); atrial septal defect (n = 3); and prophylactic patent foramen ovale closure in a scuba diver (n = 1). Successful closure occurred in 76% of patients (n = 53). Compared with those patients with successful transcatheter closure, the mean septal excursion in patients with failed closure was 0.66 +/- 0.56 cm versus 0.76 +/- 0.47 cm (P = not significant [NS]). Conclusion: Our results do not support the concern that exaggerated septal mobility compromises successful device closure of interatrial communications. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, 55 Fruit St,VBK 508, Boston, MA 02114 USA. RI McQuillan, Brendan/B-8271-2013; OI McQuillan, Brendan/0000-0002-2130-8114; Picard, Michael/0000-0002-9264-3243 NR 6 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD NOV PY 2003 VL 20 IS 8 BP 711 EP 714 DI 10.1111/j.0742-2822.2003.02173.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 752BN UT WOS:000187126900003 PM 14641375 ER PT J AU Talora, C Campese, AF Bellavia, D Pascucci, M Checquolo, S Groppioni, M Frati, L von Boehmer, H Gulino, A Screpanti, I AF Talora, C Campese, AF Bellavia, D Pascucci, M Checquolo, S Groppioni, M Frati, L von Boehmer, H Gulino, A Screpanti, I TI Pre-TCR-triggered ERK signalling-dependent downregulation of E2A activity in Notch3-induced T-cell lymphoma SO EMBO REPORTS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NF-KAPPA-B; PT-ALPHA; EXPRESSION; NOTCH; GENE; PROTEINS; RECEPTOR; MICE; ACTIVATION AB Notch and basic helix - loop - helix E2A pathways specify cell fate and regulate neoplastic transformation in a variety of cell types. Whereas Notch enhances tumorigenesis, E2A suppresses it. However, whether and how Notch and E2A interact functionally in an integrative mechanism for regulating neoplastic transformation remains to be understood. It has been shown that Notch3-induced T-cell leukaemia is abrogated by the inactivation of pTalpha/pre-T-cell antigen receptor (pre-TCR). We report here that Notch3-induced transcriptional activation of pTalpha/pre- TCR is responsible for the downregulation of E2A DNA binding and transcriptional activity. Further, the E2A messenger RNA and protein levels remain unaltered but the E2A inhibitor Id1 expression is augmented in thymocytes and T lymphoma cells derived from Notch3 transgenic mice. The increase in Id1 expression is achieved by pre-TCR-induced extracellular-signalling-regulated kinase 1/2. These observations support a model in which the upregulation of pre-TCR signalling seems to be the prerequisite for Notch3-induced inhibition of E2A, thus leading to the development of lymphoma in Notch3 transgenic mice. C1 Univ Roma La Sapienza, Dept Expt Med & Pathol, Lab Mol Pathol, I-00161 Rome, Italy. Neuromed Inst, I-86077 Pozzilli, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Pasteur, Fdn Cenci Bolognetti, I-00161 Rome, Italy. RP Screpanti, I (reprint author), Univ Roma La Sapienza, Dept Expt Med & Pathol, Lab Mol Pathol, Viale Regina Elena 324, I-00161 Rome, Italy. RI Campese, Antonio /A-9783-2015; OI CAMPESE, Antonio Francesco/0000-0002-8535-6609 NR 23 TC 58 Z9 58 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD NOV PY 2003 VL 4 IS 11 BP 1067 EP 1072 DI 10.1038/sj.embor.7400013 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 739KC UT WOS:000186342800014 PM 14566327 ER PT J AU Weber, SG Gold, HS Hooper, DC Karchmer, AW Carmeli, Y AF Weber, SG Gold, HS Hooper, DC Karchmer, AW Carmeli, Y TI Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in hospitalized patients SO EMERGING INFECTIOUS DISEASES LA English DT Article ID FIBRONECTIN-BINDING PROTEINS; CONTROL-GROUP SELECTION; ANTIBIOTIC-RESISTANCE; SUBINHIBITORY LEVELS; ESCHERICHIA-COLI; SUSCEPTIBILITY; CIPROFLOXACIN; EPIDEMIOLOGY; INFECTIONS; EMERGENCE AB To determine whether fluoroquinolone exposure is a risk factor for the isolation of Staphylococcus aureus and whether the effect is different for methicillin-resistant S. aureus (MRSA) versus methicillin-susceptible S. aureus (MSSA), we studied two case groups. The first case group included 222 patients with nosocomially acquired MRSA. The second case group included 163 patients with nosocomially acquired MSSA. A total of 343 patients admitted concurrently served as controls. Outcome measures were the adjusted odds ratio (OR) for isolation of MRSA and MSSA after fluoroquinolone exposure. Exposure to both levofloxacin (OR 5.4; p < 0.0001) and ciprofloxacin (OR 2.2; p < 0.003) was associated with isolation of MRSA but not MSSA. After adjustment for multiple variables, both drugs remained risk factors for MRSA (levofloxacin OR 3.4; p < 0.0001; ciprofloxacin OR 2.5; p = 0.005) but not MSSA. Exposure to levofloxacin or ciprofloxacin is a significant risk factor for the isolation of MRSA, but not MSSA. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weber, SG (reprint author), Univ Chicago Hosp, Infect Dis Sect, 5847 S Maryland Ave,MC 5065, Chicago, IL 60637 USA. NR 28 TC 213 Z9 216 U1 0 U2 3 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2003 VL 9 IS 11 BP 1415 EP 1422 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 740CV UT WOS:000186384400010 PM 14718085 ER PT J AU Williams, DL Bowers, RR Bartness, TJ Kaplan, JM Grill, HJ AF Williams, DL Bowers, RR Bartness, TJ Kaplan, JM Grill, HJ TI Brainstem melanocortin 3/4 receptor stimulation increases uncoupling protein gene expression in brown fat SO ENDOCRINOLOGY LA English DT Article ID ROSTRAL VENTROLATERAL MEDULLA; NUCLEUS-TRACTUS-SOLITARIUS; CENTRAL-NERVOUS-SYSTEM; AGOUTI-RELATED PROTEIN; BETA-ENDORPHIN; MESSENGER-RNA; ADAPTIVE THERMOGENESIS; ADIPOSE-TISSUE; HORMONE GENE; BODY-WEIGHT AB Central administration of melanocortin 3 and 4 receptor (MC3/4-R) agonists increases energy expenditure, with the hypothalamus commonly held as the primary site of action. It is also clear, however, that MC4-R are expressed in caudal brainstem structures of relevance to the control of energy expenditure. Three experiments investigated whether hindbrain MC-R contribute to the energy expenditure effects of central MC3/4-R agonist treatments; in each, we examined the effect of fourth intracerebroventricular (icv) administration of a MC3/4-R agonist, MTII ( three injections, each separated by 12 h), on uncoupling protein 1 (UCP-1) gene expression in brown adipose tissue ( BAT). First, we compared the effects of fourth and third icv administration of MTII and found that the hindbrain and forebrain treatments were equally effective at elevating UCP-mRNA expression in BAT compared with the respective vehicle-treated group results. A second experiment demonstrated that the fourth icv MTII-induced rise in UCP-1 expression was mediated by sympathetic outflow to BAT by showing that this response was abolished by surgical denervation of BAT. In the third experiment, we showed that chronic decerebrate rats, like their neurologically intact controls, elevated UCP-1 mRNA expression in response to fourth icv MTII administration. Taken together, the results indicate that: 1) there is an independent caudal brainstem MC3/4-R trigger for a sympathetically stimulated elevation in BAT UCP-1 gene expression, and 2) the MTII-induced rise in UCP-1 expression can be mediated by circuitry intrinsic to the caudal brainstem and spinal cord. C1 Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. RP Williams, DL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111 Endo, Seattle, WA 98108 USA. RI Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 FU NIDDK NIH HHS [DK-21397, DK-42284, DK32524] NR 50 TC 71 Z9 71 U1 1 U2 2 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 NOV PY 2003 VL 144 IS 11 BP 4692 EP 4697 DI 10.1210/en.2003-0440 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 736PB UT WOS:000186178300004 PM 12960080 ER PT J AU Leech, CA Habener, JF AF Leech, CA Habener, JF TI Regulation of glucagon-like peptide-1 receptor and calcium-sensing receptor signaling by L-histidine SO ENDOCRINOLOGY LA English DT Article ID PANCREATIC BETA-CELL; EXTRACELLULAR CA2+-SENSING RECEPTOR; INSULIN-SECRETION; MOLECULAR-CLONING; CA2+ CHANNELS; AMINO-ACIDS; RAT-KIDNEY; B-CELLS; RELEASE; EXPRESSION AB Receptor-specific agonists of the extracellular calcium-sensing receptor (CaSR) potentiate glucose-induced insulin secretion, an effect similar to that of glucagon-like peptide-1 (GLP-1). We have sequenced the full open reading frame of the CaSR from rat insulinoma (INS-1) cells and find that the predicted amino acid sequence of the receptor is identical with that of the receptor from the parathyroid gland. This receptor couples to both Gq/11 and Gi/o, and this dual coupling may partly explain the varying effects of nonspecific agonists on secretion reported previously. L-Histidine (L-His) increases the sensitivity of the CaSR to extracellular Ca2+ and potentiates glucose-dependent insulin secretion from INS-1 cells. This potentiation is partially inhibited at low extracellular [Ca2+] where the CaSR is ineffective. Coexpression of the CaSR and GLP-1 receptor (GLP-1R) produces a pertussis toxin-sensitive inhibition of GLP-1-induced cAMP production in response to elevated extracellular [Ca2+]. However, L-His potentiates cAMP response element reporter activity in INS-1 cells and in human embryonic kidney-293 cells expressing either the GLP-1R alone or the CaSR and GLP-1R. INS-1 cells express the RNA for the CaSR at a lower level than that for the GLP-1R. This difference in expression level of the receptors may explain the potentiation of insulin secretion by L-His despite coupling of the CaSR to Gi/o. In conclusion, L-His can potentiate both GLP-1R- and CaSR-activated signaling pathways, and these effects may play a role in the potentiation of glucose-induced insulin secretion in response to meals containing protein in addition to carbohydrates and fat. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Leech, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, 50 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK30834] NR 31 TC 13 Z9 13 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2003 VL 144 IS 11 BP 4851 EP 4858 DI 10.1210/en.2003-0498 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 736PB UT WOS:000186178300027 PM 12959987 ER PT J AU Garshick, E Laden, F Hart, JE Caron, A AF Garshick, E Laden, F Hart, JE Caron, A TI Residence near a major road and respiratory symptoms in US veterans SO EPIDEMIOLOGY LA English DT Article DE respiratory symptoms; traffic; GIS; air pollution; mobile sources; adults ID PARTICULATE AIR-POLLUTION; BUS GARAGE WORKERS; DIESEL EXHAUST; AUTOMOBILE EXHAUST; TRAFFIC DENSITY; SCHOOL-CHILDREN; COAL-MINERS; EXPOSURE; ASTHMA; MORTALITY AB Background: There is evidence that exposure to motor vehicle exhaust is associated with respiratory disease. Studies in children have observed associations with wheeze, hospital admissions for asthma, and decrements in pulmonary function. However, a relationship of adult respiratory disease with exposure to vehicular traffic has not been established. Methods: We studied a sample of U.S. mate veterans drawn from the general population of southeastern Massachusetts. Information on respiratory symptoms and potential risk factors was collected by questionnaire. We assessed distance from residential addresses to major roadways using geographic information system methodology. Results: Adjusting for cigarette smoking, age, and occupational exposure to dust, men living within 50 m of a major roadway were more likely to report persistent wheeze (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0-1.7) compared with those living more than 400 in away. The risk was observed only for those living within 50 m of heavily trafficked roads (greater than or equal to10,000 vehicles/24 h): OR = 1.7; CI = 1.2-2.4). The risk of patients experiencing chronic phlegm while living on heavily trafficked roads also increased (OR = 1.4; CI = 1.0-2.0), although there was little evidence for an association with chronic cough. This association was not dependent on preexisting doctor-diagnosed chronic respiratory or heart disease. Conclusions: Exposure to vehicular emissions by living near busy roadways might contribute to symptoms of chronic respiratory disease in adults. C1 VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv & Res Serv, Boston, MA 02132 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Environm Epidemiol Program, Dept Environm Hlth, Boston, MA 02115 USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv & Res Serv, 1400 VFW Pkwy, Boston, MA 02132 USA. RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NCI NIH HHS [R01 CA090792, R01 CA90792] NR 39 TC 61 Z9 63 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2003 VL 14 IS 6 BP 728 EP 736 DI 10.1097/01.ede.0000082045.50073.66 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 736FG UT WOS:000186160300015 PM 14569190 ER PT J AU Gong, MN Sai, Y Zhou, W Thompson, BT Xu, LL Christiani, DC AF Gong, MN Sai, Y Zhou, W Thompson, BT Xu, LL Christiani, DC TI Genotyping patients with recent blood transfusions SO EPIDEMIOLOGY LA English DT Article DE blood transfusion; polymorphism (genetics); intensive-care unit; polymerase chain reaction ID RESPIRATORY-DISTRESS-SYNDROME; POLYMERASE-CHAIN-REACTION; GENE POLYMORPHISM; TRAUMA PATIENTS; SEVERE SEPSIS; SEPTIC SHOCK; DNA; MICROCHIMERISM; RECIPIENTS; SUSCEPTIBILITY AB Background: Many studies have used polymerase chain reaction amplification (PCR) to genotype for common polymorphisms in intensive-care units (ICUs) where blood transfusions are common. Evidence that donor leukocytes in transfused blood can be detected by PCR of the recipient blood suggests that this minor population of donor white cells (microchimerism) can interfere with genotyping of allelic polymorphisms in critically ill transfused patients. To investigate this possibility, we assayed DNA extracted from the blood and buccal cells of ICU patients for 2 common polymorphisms in the TNF-beta gene and the surfactant protein-B (SP-B) gene. Methods: Study subjects were ICU patients from the Massachusetts General Hospital (Boston, MA) enrolled into a study on the molecular epidemiology of acute respiratory distress syndrome between January 1999 and October 2000. Blood and buccal cells were collected and DNA was extracted from 145 patients. Genotyping was performed by enzyme digestion and pyrosequencing. Results: The Kappa statistics comparing the genotype results from blood and buccal cells were 0.98 (95% confidence interval [CI] = 0.94-1.01) for TNFB and 0.95 (CI = 0.87-1.02) for SP-B. When the analysis was restricted only to the 107 patients who were transfused, the Kappa statistic remained high at 0.97 (CI = 0.93-1.01) for TNFB and 0.93 (CI = 0.84-1.03) for SP-B. Conclusion: We conclude that microchimerism from allogeneic blood transfusion is unlikely to have major effects on the genotype results of common polymorphisms in large molecular epidemiology studies conducted in the critical care setting if DNA is collected within a day after transfusions. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Pulm & Crit Care Unit, Dept Med,Massachusetts Gen Hosp, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [K23HL67197, K23 HL067197-01, K23 HL067197, K23 HL067197-02, R01 HL060710, R01 HL60710]; NIEHS NIH HHS [P30 ES000002, T32 ES007069, T32 ES07069, ES00002] NR 23 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2003 VL 14 IS 6 BP 744 EP 747 DI 10.1097/01.ede.0000091680.23304.21 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 736FG UT WOS:000186160300019 PM 14569193 ER PT J AU Sui, JH Bai, JR Tallarico, AS Xu, C Marasco, WA AF Sui, JH Bai, JR Tallarico, AS Xu, C Marasco, WA TI Identification of CD4 and transferrin receptor antibodies by CXCR4 antibody-guided Pathfinder selection SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE CXCR4; Pathfinder selection; phage display; scFv; transferrin receptor ID PHAGE DISPLAY TECHNOLOGY; SINGLE-CHAIN FV; MONOCLONAL-ANTIBODY; CHEMOKINE RECEPTOR; LIGAND-BINDING; HIV-1 ENTRY; CELL-LINES; LIBRARY; CCR5; TUMOR AB To generate human antibodies against CXCR4, a seven-transmembrane chemokine receptor and a principal coreceptor for HIV-1, several rounds of Pathfinder and Step-back selection from a large phage display antibody library were performed on Jurkat cells. A mAb against CXCR4 or biotinyated phage antibodies were used as guide molecules. Over 100 pan-Jurkat-cell-positive antibodies were characterized, but none were CXCR4 specific. However, several antibodies against CD4 and the transferrin receptor were identified. Our results indicate that, although Pathfinder and Step-back selection can be used to select phage antibodies on whole cells, the successful selection of certain targets is still complex and limited. The reason is probably, in part, due to the inaccessibility of the targeted extracellular structures and the range of the horseradish peroxidase-labeled guide molecule. Refinements of these techniques are required to improve target specificity and selectivity. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 824,44 Binney St, Boston, MA 02115 USA. OI SUI, JIANHUA/0000-0002-1272-9662 NR 35 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV PY 2003 VL 270 IS 22 BP 4497 EP 4506 DI 10.1046/j.1432-1033.2003.03843.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737XW UT WOS:000186258500011 PM 14622278 ER PT J AU Ostrow, JD Pascolo, L Shapiro, SM Tiribelli, C AF Ostrow, JD Pascolo, L Shapiro, SM Tiribelli, C TI New concepts in bilirubin encephalopathy SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Review DE bilirubin; jaundice; neonates; nuerotoxicity; encephalopathy; kernicterus ID RESISTANCE-ASSOCIATED PROTEIN; APOPTOSIS INHIBITORY PROTEIN; CENTRAL-NERVOUS-SYSTEM; BRAIN-STEM RESPONSES; JAUNDICED GUNN-RATS; EVOKED-POTENTIAL ABNORMALITIES; GLUTATHIONE-S-TRANSFERASES; ORGANIC ANION TRANSPORTER; MDR1 P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE AB Revised concepts of bilirubin encephalopathy have been revealed by studies of bilirubin toxicity in cultured CNS cells and in congenitally jaundiced Gunn rats. Bilirubin neurotoxicity is related to the unbound (free) fraction of unconjugated bilirubin (B-f), of which the dominant species at physiological pH is the protonated diacid, which can passively diffuse across cell membranes. As the binding affinity of plasma albumin for bilirubin decreases strikingly as albumin concentration increases, previously reported B-f values were underestimated. Newer diagnostic tests can detect reversible neurotoxicity before permanent damage occurs from precipitation of bilirubin (kernicterus). Early toxicity can occur at B-f only modestly above aqueous saturation and affects astrocytes and neurons, causing mitochondrial damage, resulting in impaired energy metabolism and apoptosis, plus cell-membrane perturbation, which causes enzyme leakage and hampers transport of neurotransmitters. The concentrations of unbound bilirubin in the cerebro-spinal fluid and CNS cells are probably limited mainly by active export of bilirubin back into plasma, mediated by ABC transporters present in the brain capillary endothelium and choroid plexus epithelium. Intracellular bilirubin levels may be diminished also by oxidation, conjugation and binding to cytosolic proteins. These new concepts may explain the varied susceptibility of neonates to develop encephalopathy at any given plasma bilirubin level and the selective distribution of CNS lesions in bilirubin encephalopathy. They also can suggest better strategies for predicting, preventing and treating this syndrome. C1 Univ Washington, Sch Med, Dept Med, GI Hepatol Div, Seattle, WA 98195 USA. Univ Trieste, Liver Res Ctr, Trieste, Italy. Univ Trieste, Dept BBCM, Trieste, Italy. Virginia Commonwealth Univ, Med Coll Virginia, Dept Neurol, Div Pediat Neurol, Richmond, VA 23298 USA. RP Ostrow, JD (reprint author), VA Puget Sound Hlth Care Syst, Res Serv 151 L, Seattle Div, 1600 S Columbian Way, Seattle, WA 98108 USA. FU NIDCD NIH HHS [R01-DC00369] NR 149 TC 78 Z9 84 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD NOV PY 2003 VL 33 IS 11 BP 988 EP 997 DI 10.1046/j.1365-2362.2003.01261.x PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 737NA UT WOS:000186237600009 PM 14636303 ER PT J AU Rodig, N Ryan, T Allen, JA Pang, H Grabie, N Chernova, T Greenfield, EA Liang, SC Sharpe, AH Lichtman, AH Freeman, GJ AF Rodig, N Ryan, T Allen, JA Pang, H Grabie, N Chernova, T Greenfield, EA Liang, SC Sharpe, AH Lichtman, AH Freeman, GJ TI Endothelial expression of PD-L1 and PD-L2 down-regulates CD8(+) T cell activation and cytolysis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocytes; endothelial cells; costimulation ID HUMAN VASCULAR ENDOTHELIUM; DENDRITIC CELLS; B7 FAMILY; CYTOKINE PRODUCTION; IFN-GAMMA; COSTIMULATION; RESPONSES; DIFFERENTIATION; INDUCTION; MECHANISM AB Interactions between CD8(+) T cells and endothelial cells are important in both protective and pathologic immune responses. Endothelial cells regulate the recruitment of CD8(+) T cells into tissues, and the activation of CD8+ T cells by antigen presentation and costimulatory signals. PD-L1 and PD-L2 are recently described B7-family molecules which bind to PD-1 on activated lymphocytes and down-regulate T cell activation. We found that PD-L1 is expressed on interferon-gamma stimulated cultured human and mouse endothelial cells, while PD-L2 was found on stimulated human but not mouse endothelial cells. Expression was further upregulated by TNF-alpha. Antibody blockade of endothelial cell PD-L1 and PD-L2 enhanced endothelial cell costimulation of PHA-activated human CD8(+) T cells. Antibody blockade of mouse endothelial cell PD-L1 enhanced both IFN-gamma secretion and cytolytic activity of CD8(+) T cells in response to endothelial cell antigen presentation. These results show that IFN-gamma activated endothelial cells can inhibit T cell activation via expression of the immunoinhibitory PD-L1 and PD-L2 molecules. Endothelial expression of PD-ligands would allow activation and extravasation of T cells without excessive vessel damage. Our findings highlight a potentially important pathway by which endothelial cells down-regulate CD8(+) T cell-mediated immune responses. C1 Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Lichtman, AH (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [CA84500]; NHLBI NIH HHS [HL36028, HL72056]; NIAID NIH HHS [AI39671, AI41584, AI46414] NR 42 TC 190 Z9 200 U1 2 U2 9 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 NOV PY 2003 VL 33 IS 11 BP 3117 EP 3126 DI 10.1002/eji.200324270 PG 10 WC Immunology SC Immunology GA 741GK UT WOS:000186450200018 PM 14579280 ER PT J AU Visser, K Bosch, JL Leiner, T van Engelshoven, JMA Passchier, J Hunink, MGM AF Visser, K Bosch, JL Leiner, T van Engelshoven, JMA Passchier, J Hunink, MGM TI Patients' preferences for MR angiography and duplex US in the work-up of peripheral arterial disease SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE patient preferences assessment; diagnostic work-up; peripheral arterial disease; magnetic resonance; duplex ultrasound ID COST-EFFECTIVENESS; INTERMITTENT CLAUDICATION; RADIOLOGY; EUROQOL AB Purpose. To measure patients' preferences for magnetic resonance (MR) angiography and duplex ultrasound (US) in the imaging work-up of peripheral arterial disease (PAD). Methods. Ninety-eight patients, who underwent both MR angiography and duplex US, received a questionnaire by mail and their preferences for imaging- work-up were assessed in a telephone interview. The questionnaire consisted of one question on which imaging test they preferred, a rating scale score ranging from 0 (not bothersome at all) to 10 (extremely bothersome), and specific questions on whether patients experienced discomfort due to the imaging work-up. Responses were presented as means and frequencies, and differences were tested by non-parametric tests. Results. Half of the patient population (50%) had no preference for MR angiography or duplex US, 41% had a preference for MR angiography, and 9% had a preference for duplex US. The average rating scale scores for MR angiography (1.6) and duplex US (1.7) were not significantly different (p = 0.53). Four out of 98 (4%) patients responded that they experienced pain during the MR angiography versus 18 (18%) for duplex US (p = 0.001). Eight out of 98 (8%) patients responded that they were anxious during the MR angiography versus 1(1%) for duplex US (p = 0.02). Conclusion. The results suggest that the majority of patients have no preference between MR angiography and duplex US in the diagnostic work-up of PAD. Among patients who do have a preference, MR angiography was preferred over duplex us. C1 Univ Rotterdam, Med Ctr, Erasmus MC,ART Program, Dept Epidemiol & Biostat, NL-3015 GE Rotterdam, Netherlands. Univ Rotterdam, Med Ctr, Dept Radiol, NL-3015 GE Rotterdam, Netherlands. Univ Rotterdam, Med Ctr, Dept Med Psychol & Psychotherapy, NL-3015 GE Rotterdam, Netherlands. State Univ Limburg Hosp, Dept Radiol, NL-6201 BX Maastricht, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Hunink, MGM (reprint author), Univ Rotterdam, Med Ctr, Erasmus MC,ART Program, Dept Epidemiol & Biostat, Room EE21-40A,Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. NR 11 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD NOV PY 2003 VL 26 IS 5 BP 537 EP 543 DI 10.1016/S1078-5884(03)00387-3 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 738GR UT WOS:000186278800012 PM 14532883 ER PT J AU Barger, JL Walford, RL Weindruch, R AF Barger, JL Walford, RL Weindruch, R TI The retardation of aging by caloric restriction: its significance in the transgenic era SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE aging; dwarf mice; insulin-like growth factor-1; growth hormone; transgenic mice ID AMES DWARF MICE; LIFE-SPAN EXTENSION; GROWTH-FACTOR-I; INSULIN-RECEPTOR; OXIDATIVE STRESS; DROSOPHILA-MELANOGASTER; EXTENDED LONGEVITY; SIGNALING PATHWAY; ADIPOSE-TISSUE; HORMONE AB The retardation of aging and diseases by caloric restriction (CR) is a widely-studied and robust phenomenon. Recent publications describe transgenic and other mutant rodents displaying lifespan extension, and the rapid pace at which these animals are being generated raises the possibility that the importance of the CR paradigm is declining. Here we discuss these models and evaluate the evidence whether or not the aging process is retarded based on longevity, disease patterns and age-associated biological changes. A comparison to rodents on CR is made. Because CR has been investigated for similar to70 years with increasing intensity, there exists extensive data to document aging retardation. In contrast, for nearly all of the genetically abnormal models of lifespan extension, such data are minimal and often unconvincing; additional studies will be required to validate these strains as suitable models for aging research. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. RP Weindruch, R (reprint author), Univ Wisconsin, William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, 2500 Overlook Terrace, Madison, WI 53705 USA. EM rhweindr@wisc.edu OI Barger, Jamie/0000-0001-8694-0068 FU NIA NIH HHS [T32AG00213, P01 AG11915, R01 AG18922] NR 44 TC 102 Z9 105 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 2003 VL 38 IS 11-12 BP 1343 EP 1351 DI 10.1016/j.exger.2003.10.017 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 766ZC UT WOS:000188412800015 PM 14698815 ER PT J AU Liang, HY Masoro, EJ Nelson, JF Strong, R McMahon, CA Richardson, A AF Liang, HY Masoro, EJ Nelson, JF Strong, R McMahon, CA Richardson, A TI Genetic mouse models of extended lifespan SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE dwarf mice; caloric restriction; insulin like growth factor-I; insulin receptor; growth hormone receptor binding protein ID RECEPTOR/BINDING PROTEIN GENE; AMES DWARF MICE; GROWTH-HORMONE LEVELS; FED AD-LIBITUM; OXIDATIVE STRESS; SIGNALING PATHWAY; CALORIC RESTRICTION; DIETARY RESTRICTION; INSULIN-RECEPTOR; DISRUPTED MICE AB Since 1996, seven genetic mouse models have been reported to show increased lifespan: Ames and Snell dwarf mice, the 'little mouse' (Ghrhr(lit/lit)), mice null for either growth hormone receptor/binding protein (GHR/BP-/-) or p66(shc) (p66(shc-/-)), mice heterozygous for the IGF-I receptor (Igflr(+/-)), and fat-specific insulin receptor knockout mice. In this article, we describe and evaluate these mouse models with respect to their relevance for aging studies. While these seven genetic models all show a significant increase in lifespan, issues of sample size and animal husbandry procedures require further evaluation before firm conclusions can be drawn on the reproducibility of life extension in most of these mouse models. Because data on the age-related pathology and physiological functions are lacking for all of the models, except the dwarf mice, it is too early to conclude that aging is retarded in these mouse models. However, these mouse models are already providing new information about the mechanism underlying mammalian aging. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78284 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr,MSC 7762, San Antonio, TX 78229 USA. EM richardsona@uthscsa.edu RI Liang, Hanyu/A-1066-2010 NR 79 TC 137 Z9 139 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 2003 VL 38 IS 11-12 BP 1353 EP 1364 DI 10.1016/j.exger.2003.10.019 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 766ZC UT WOS:000188412800016 PM 14698816 ER PT J AU Kyba, M Daley, GQ AF Kyba, M Daley, GQ TI Hematopoiesis from embryonic stem cells: Lessons from and for ontogeny SO EXPERIMENTAL HEMATOLOGY LA English DT Review ID MURINE YOLK-SAC; PRIMORDIAL GERM-CELLS; COLONY-FORMING CELLS; IN-VITRO GENERATION; MOUSE EMBRYO; BONE-MARROW; DEFINITIVE HEMATOPOIESIS; ENDOTHELIAL-CELLS; BCR-ABL; LYMPHOHEMATOPOIETIC CELLS AB Cellular therapies derived from embryonic stem (ES) cells have acquired new interest and urgency with the demonstration that embryonic stem cells can be established from human blastocyst-stage embryos. Our ability to derive therapeutic cells from differentiating ES cell cultures will ultimately depend on our understanding of the embryonic developmental processes that direct the differentiation of pluripotent cells into transplantable lineage-specific stem cells, and on our ability to recapitulate these processes in vitro. In this review, we evaluate the work that has been done to date on the hematopoietic differentiation of ES cells, and discuss this in the context of what is known about the embryonic origin of the hematopoietic stem cell. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Ctr Dev Biol, Dallas, TX USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst, Cambridge Ctr 9, Cambridge, MA 02142 USA. EM daley@wi.mit.edu OI Kyba, Michael/0000-0002-5579-7534 FU NCI NIH HHS [CA86991, CA76418]; NHLBI NIH HHS [HL71265]; NIDDK NIH HHS [DK59279] NR 121 TC 45 Z9 48 U1 2 U2 6 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 NOV PY 2003 VL 31 IS 11 BP 994 EP 1006 DI 10.1016/j.exphem.2003.08.002 PG 13 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 814HD UT WOS:000220964900002 PM 14585361 ER PT J AU Saunders, AJ Tanzi, RE AF Saunders, AJ Tanzi, RE TI Welcome to the complex disease world Alpha2-macroglobulin and Alzheimer's disease SO EXPERIMENTAL NEUROLOGY LA English DT Editorial Material ID BETA-AMYLOID PEPTIDE; ALPHA-2-MACROGLOBULIN I1000V POLYMORPHISM; DELETION POLYMORPHISM; GENETIC ASSOCIATION; FIBRIL FORMATION; ONSET; ALPHA(2)-MACROGLOBULIN; CHROMOSOME-12; LOCUS; HETEROGENEITY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Genet & Aging Res Unit, Dept Neurol,Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. Drexel Univ, Dept Biosci, Philadelphia, PA 19104 USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Genet & Aging Res Unit, Dept Neurol,Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. NR 39 TC 10 Z9 11 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2003 VL 184 IS 1 BP 50 EP 53 DI 10.1016/j.expneurol.2003.09.004 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 747KZ UT WOS:000186804800011 PM 14637079 ER PT J AU Bibbiani, F Oh, JD Petzer, JP Castagnoli, N Chen, JF Schwarzschild, MA Chase, TN AF Bibbiani, F Oh, JD Petzer, JP Castagnoli, N Chen, JF Schwarzschild, MA Chase, TN TI A(2A) antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Parkinson's disease; A(2A) receptor; KW-6002; MPTP; dyskinesia; PKA; primates; rodents ID PROTEIN-KINASE-A; CENTRAL-NERVOUS-SYSTEM; RECEPTOR ANTAGONIST; ADENOSINE RECEPTORS; IN-VIVO; PHOSPHORYLATION SITES; AMPA RECEPTORS; RAT; MONKEYS; DYSKINESIA AB Adenosine A(2A) receptors, abundantly expressed on striatal medium spiny neurons, appear to activate signaling cascades implicated in the regulation of coexpressed ionotropic glutamatergic receptors. To evaluate the contribution of adenosinergic mechanisms to the pathogenesis of the response alterations induced by dopaminergic treatment, we studied the ability of the selective adenosine A(2A) receptor antagonist KW-6002 to prevent as well as palliate these syndromes in rodent and primate models of Parkinson's disease. In rats, KW-6002 reversed the shortened motor response produced by chronic levodopa treatment while reducing levodopa-induced hyperphosphorylation at S845 residues on AMPA receptor GluR1 subunits. In primates, KW-6002 evidenced modest antiparkinsonian activity when given alone. Once-daily coadministration of KW-6002 with apomorphine prevented the development of dyskinesias, which appeared in control animals 7-10 days after initiating apomorphine treatment. Animals initially given apornorphine plus KW-6002 for 3 weeks did not begin to manifest apomorphine-induced dyskinesias until 10-12 days after discontinuing the A(2A) antagonist. These results suggest that KW-6002 can attenuate the induction as well as the expression of motor response alterations to chronic dopaminergic stimulation in parkinsonian animals, possibly by blocking A(2A) receptor-stimulated signaling pathways. Our findings strengthen the rationale for developing A(2A) antagonists as an early treatment strategy for Parkinson's disease. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Natl Inst Neurol Disorders & Stroke, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Mol Neurobiol Lab, Boston, MA 02114 USA. Virginia Tech, Dept Chem, Blacksburg, VA USA. Cent Michigan Univ, Dept Psychol, Mt Pleasant, MI 48859 USA. RP Chase, TN (reprint author), Natl Inst Neurol Disorders & Stroke, Expt Therapeut Branch, NIH, Bldg 10,Room 5C103, Bethesda, MD 20892 USA. RI Petzer, Jacobus/E-8747-2011; OI Petzer, Jacobus/0000-0002-7114-8120 NR 52 TC 135 Z9 138 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2003 VL 184 IS 1 BP 285 EP 294 DI 10.1016/S0014-4886(03)00250-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 747KZ UT WOS:000186804800031 PM 14637099 ER PT J AU Stackman, RW Eckenstein, F Frei, B Kulhanek, D Nowlin, J Quinn, JF AF Stackman, RW Eckenstein, F Frei, B Kulhanek, D Nowlin, J Quinn, JF TI Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment SO EXPERIMENTAL NEUROLOGY LA English DT Article DE amyloid; oxidative stress; spatial learning; spatial memory; hippocampus; Alzheimer; Tg2576; antioxidant ID AMYLOID-BETA-PROTEIN; EXTRACT EGB 761; HEALTHY-YOUNG VOLUNTEERS; GLOBAL BRAIN ISCHEMIA; RAT HIPPOCAMPAL CELLS; OXIDATIVE STRESS; IN-VIVO; A-BETA; PHOSPHOLIPID BREAKDOWN; GINSENG COMBINATION AB Alzheimer's disease (AD) is characterized by cognitive decline and deposition of beta-amyloid (Abeta) plaques in cortex and hippocampus. A transgenic mouse AD model (Tg2576) that overexpresses a mutant form of human Abeta precursor protein exhibits age-related cognitive deficits, Abeta plaque deposition, and oxidative damage in the brain. We tested the ability of Ginkgo biloba, a flavonoid-rich antioxidant, to antagonize the age-related behavioral impairment and neuropathology exhibited by Tg2576 mice. At 8 months of age, 16 female Tg2576 and 15 female wild-type (wt) littermate mice were given ad lib access to tap water or Ginkgo biloba (70 mg/kg/day in water). After 6 months of treatment, all mice received Morris water maze training (4 trials/day for 10 days) to assess hippocampal dependent spatial learning. All mice received a 60-s probe test of spatial memory retention 24 It after the 40th trial. Untreated Tg2576 mice exhibited a spatial learning impairment, relative to wt mice, while Ginkgo biloba-treated Tg2576 mice exhibited spatial memory retention comparable to wt during the probe test. Spatial learning was not different between Ginkgo biloba-treated and untreated wt mice. There were no group differences in learning to swim to a visible platform. Soluble Abeta and hippocampal Abeta plaque burden did not differ between the Tg2576 groups. Brain levels of protein carbonyls were paradoxically elevated in Ginkgo biloba-treated mice. These data indicate that chronic Ginkgo biloba treatment can block an age-dependent decline in spatial cognition without altering Abeta levels and without suppressing protein oxidation in a transgenic mouse model of AD. (C) 2003 Elsevier Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon State Univ, Linus Pauling Inst Sci & Med, Corvallis, OR 97331 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Stackman, RW (reprint author), Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. OI Stackman Jr, Robert/0000-0002-5950-046X FU NCCIH NIH HHS [NIH-AT00066]; NIA NIH HHS [NIA AG08017, AG07424] NR 81 TC 144 Z9 159 U1 2 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2003 VL 184 IS 1 BP 510 EP 520 DI 10.1016/S0014-4886(03)00399-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 747KZ UT WOS:000186804800052 PM 14637120 ER PT J AU Ledoux, WR Shofer, JB Ahroni, JH Smith, DG Sangeorzan, BJ Boyko, EJ AF Ledoux, WR Shofer, JB Ahroni, JH Smith, DG Sangeorzan, BJ Boyko, EJ TI Biomechanical differences among pes cavus, neutrally aligned, and pes planus feet in subjects with diabetes SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE diabetes mellitus; flatfoot; foot deformities ID MEDIAL LONGITUDINAL ARCH; FOOT; RELIABILITY AB The purpose of this study was to quantify differences in joint range of motion, foot deformity, and foot morphology among pes cavus, neutrally aligned, pes planus rigid, and pes planus flexible feet. A cohort of 1047 veterans with diabetes (contributing 2047 feet) was enrolled in a prospective study of diabetic ulcer risk factors (the Seattle Diabetic Foot Study). Significant differences between foot types were found. Pes cavus feet had an increased percentage of prominent metatarsal heads, bony prominences, and hammer/claw toes (p < .0001), as well as significantly increased amounts of hallux dorsiflexion and decreased amounts of hallux plantarflexion (p < .0001) with a total range of motion equal to the other foot types (p = .3). Neutrally aligned feet had a lower percentage of intrinsic muscle atrophy, bony prominences, and hammer/claw toes (p < .0001). Pes planus feet had an increased lateral talometatarsal angle (p < .0001) and an increased second metatarsal length. These data demonstrate structural differences between foot types in a population with diabetes. C1 VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Epidemiol Res & Informat Ctr, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Res & Dev Serv, Epidemiol Res & Informat Ctr, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Gen Internal Med Sect, Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Epidemiol Res & Informat Ctr, MS 151,1660 S Columbian Way, Seattle, WA 98108 USA. RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 25 TC 32 Z9 32 U1 0 U2 3 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD NOV PY 2003 VL 24 IS 11 BP 845 EP 850 PG 6 WC Orthopedics SC Orthopedics GA 745AH UT WOS:000186664700007 PM 14655889 ER PT J AU Rattan, R Giri, S Singh, AK Singh, I AF Rattan, R Giri, S Singh, AK Singh, I TI Rho A negatively regulates cytokine-mediated inducible nitric oxide synthase expression in brain-derived transformed cell lines: Negative regulation of IKK alpha SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE statins; RhoA; geranylgeranylation; NF-kappa B; iNOS; IKK alpha; CBP/p300; free radicals ID SMOOTH-MUSCLE-CELLS; DIFFICILE TOXIN-B; REDUCTASE INHIBITORS; MULTIPLE-SCLEROSIS; KAPPA-B; PROTEINS; INDUCTION; GTPASE; STATINS; GERANYLGERANYLATION AB The present study describes the role of RhoA as a negative regulator of iNOS expression via the inactivation of NF-kappaB in transformed brain cell lines [C-6 glioma, human astrocytoma (T98G, A172), neuroblastoma (NEB), and immortal rat astrocytes]. Treatment with lovastatin resulted in the induction of LPS/IFN-gamma-mediated iNOS mRNA and increased nitric oxide (NO) production. The addition of mevalonate and geranylgeranylpyrophosphate (GGPP) reversed the lovastatin-mediated effect, whereas FPP had no effect. An inhibitor of geranylgeranyltransferase inhibitor (GGTI 298) further induced the cytokine and lovastatin-mediated iNOS expression, suggesting the involvement of geranylgeranylated proteins in the regulation of iNOS. Bacterial toxin B (inactivates RhoA, B, and C; CDC42; Rac proteins), C3 ADP-ribosyltransferase (0) toxin from C. botulinum (inactivates RhoA, B, and C proteins), and Y-27632 (selective inhibitor of Rho-associated kinases) increased the LPS/IFN-gamma-mediated iNOS expression. Lovastatin treatment induced NO by increasing NF-kappaB translocation and its association with the CREB-binding protein (CBP/p300) via the downregulation of RhoA. Inhibition of RhoA resulted in increased activation of IKKalpha. Cotransfection studies with dominant-negative form of RhoA and iNOS-luciferase or NF-kappaB-luciferase reporter constructs further support these observations. Taken together, these studies show that downregulation of RhoA by lovastatin resulted in increased iNOS expression via the activation of NF-kappaB-CBP/p300 pathway in transformed brain cells. (C) 2003 Elsevier Inc. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Ctr, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 96 Jonathan Lucas St,316 Clin Sci Bldg, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS 37766, NS-22576, NS-34741, NS-40810] NR 35 TC 41 Z9 41 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2003 VL 35 IS 9 BP 1037 EP 1050 DI 10.1016/S0891-5849(03)00459-3 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 734JP UT WOS:000186052400005 PM 14572607 ER PT J AU Ran, QT Van Remmen, H Gu, MJ Qi, WB Roberts, LJ Prolla, T Richardson, A AF Ran, QT Van Remmen, H Gu, MJ Qi, WB Roberts, LJ Prolla, T Richardson, A TI Embryonic fibroblasts from Gpx4(+/-) mice: A novel model for studying the role of membrane peroxidation in biological processes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE phospholipid hydroperoxide glutathione peroxidase; oxidative stress; knockout mice; lipid peroxidation; free radicals ID OXIDATIVE DNA-DAMAGE; GLUTATHIONE-PEROXIDASE; LIPID-PEROXIDATION; HYDROPEROXIDE; CELLS; APOPTOSIS; MITOCHONDRIA; HEPATOCYTES; SENESCENCE; CULTURES AB A previous study using mice null for Gpx4 indicates that PHGPx plays a critical role in antioxidant defense and is essential for the survival of the mouse. In the present study, we further analyzed the stress response of MEFs (murine embryonic fibroblasts) derived from mice heterozygous for the Gpx4 gene (Gpx4(+/-) mice). MEFs from Gpx4(+/-) mice have a 50% reduction in PHGPx expression without any changes in the activities of other major antioxidant defense enzymes. Compared to MEFs from Gpx4(+/+) mice, MEFs from Gpx4(+/-) mice were more sensitive to exposure to the oxidizing agent t-butyl hydroperoxide (t-BuOOH), and t-BuOOH exposure induced increased apoptosis in MEFs from Gpx4(+/-) mice. When cultured at low cell density, MEFs from Gpx4(+/-) mice also showed retarded growth under normal culture conditions (20% oxygen) that was reversed by culturing under low oxygen (2% oxygen). In addition, oxidative damage was increased in the MEFs from the Gpx4(+/-) mice, as indicated by increased levels of F-2-isoprostanes and 8-oxo-2-deoxyguanosine in these cells. Our data demonstrate that MEFs from Gpx4(+/-) mice are more sensitive to oxidative stress because of reduced expression of PHGPx. (C) 2003 Elsevier Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Vanderbilt Univ, Dept Med & Pharmacol, Nashville, TN USA. Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, Mail Code 7756,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCI NIH HHS [CA68485]; NIA NIH HHS [AG19316, AG015908, 1P30-AG13319]; NIDDK NIH HHS [DK26657]; NIGMS NIH HHS [GM42056, GM15431] NR 29 TC 32 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2003 VL 35 IS 9 BP 1101 EP 1109 DI 10.1016/S0891-5849(03)00466-0 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 734JP UT WOS:000186052400010 PM 14572612 ER EF