FN Thomson Reuters Web of Science™ VR 1.0 PT J AU McGibbon, CA Krebs, DE Scarborough, DM AF McGibbon, CA Krebs, DE Scarborough, DM TI Vestibulopathy and age effects on head stability during chair rise SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE aging; cervicocollic reflex; chair rise; compensation; head control; vestibulopathy ID BALANCE; REFLEX; STABILIZATION; MOVEMENTS; POSTURE; FALLS; PLANE AB It is unknown how vestibular dysfunction and age differentially affect balance control during functional activities. The objective of this study was to gain insight into the effects of age and vestibulopathy on head control when rising from a chair. Head relative to trunk (head-on-trunk) sagittal plane angular and linear control strategies were studied in patients with bilateral vestibular hypofunction (BVH) and in healthy subjects aged 30-80 years. A two-way analysis of variance was used to compare head-on-trunk kinematics by age (young vs elderly) and diagnosis (healthy vs BVH) at the time of liftoff from the seat. Angular control strategies differed with age but not diagnosis: young (healthy and BVH) subjects stabilized head rotations in space while elderly (healthy and BVH) subjects stabilized head rotations on the trunk. In contrast, linear control strategies differed by diagnosis but not age: BVH subjects (young and old) allowed a greater rate of head-on-trunk translation while healthy subjects (young and old) inhibited such translations. Young BVH subjects stabilized head-in-space rotations (as did young healthy subjects) without a functioning vestibular system, suggesting cervicocollic reflex and/or other sensory compensation for vestibular loss. Elderly BVH subjects stabilized head rotation with respect to the trunk, as did healthy elders, but did not stabilize head-on-trunk translations, suggesting a reliance on passive mechanical responses of the neck to sense head movements. We conclude that compensation strategies used by patients with vestibulopathy are age-dependent and appear to be more tractable in the younger BVH patient. C1 Massachusetts Gen Hosp, Biomot Lab, Dept Orthopaed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Biomot Lab, Dept Orthopaed, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG11255] NR 25 TC 9 Z9 12 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD JAN PY 2001 VL 121 IS 1 BP 52 EP 58 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 406GB UT WOS:000167205600010 PM 11270495 ER PT J AU Voss, SE Rosowski, JJ Merchant, SN Peake, WT AF Voss, SE Rosowski, JJ Merchant, SN Peake, WT TI How do tympanic-membrane perforations affect human middle-ear sound transmission? SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE acoustics; conductive hearing loss; middle-ear mechanics; middle-ear model; otitis media; perforation size; perforation location; temporal bone measurement ID IMPEDANCE AB Although tympanic-membrane (TM) perforations are common sequelae of middle-ear disease, the hearing losses they cause have not been accurately determined, largely because additional pathological conditions occur in these ears. Our measurements of acoustic transmission before and after making controlled perforations in cadaver ears show that perforations cause frequency-dependent loss that: (1) is largest at low frequencies; (2) increases as perforation size increases; and (3) does not depend on perforation location. The dominant loss mechanism is the reduction in sound-pressure difference across the TM. Measurements of middle-ear air-space sound pressures show that transmission via direct acoustic stimulation of the oval and round windows is generally negligible. A quantitative model predicts the influence of middle-ear air-space volume on loss; with larger volumes, loss is smaller. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02144 USA. Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Voss, SE (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02144 USA. NR 15 TC 41 Z9 45 U1 0 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD JAN PY 2001 VL 121 IS 2 BP 169 EP 173 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 423PX UT WOS:000168186900012 PM 11349771 ER PT J AU Urdaniz, AP Garcia, JMS Ramos, RM Larrosa, VR Perera, JLC Terron, IM Romero, EF AF Urdaniz, AP Garcia, JMS Ramos, RM Larrosa, VR Perera, JLC Terron, IM Romero, EF TI Sociocultural aspects of the genesis of personality disorders SO ACTAS ESPANOLAS DE PSIQUIATRIA LA Spanish DT Review DE personality disorders; sociocultural aspects; postmodern age ID DEPRESSION; DIAGNOSIS; FEATURES; HEALTH AB The prevalence of personality disorders seems to be increasing in the last decades. Many sociologists and historians believe that since the end of World War II, we have seen important changes, social, cultural and economic, which could indicate that we are entering a new age. The Postmodern Age, after nearly 500 years of Modern Age. Postmodernits is characterized by an increase of the speed in all reals of life, permanent changes, materialism, dominance of capitalism as economic model, changes of roles, etc. We speculate about the possibility that the characteristics of postmodern society may be contributing to the increase of prevalence of personality disorders in general and some of them in particular. C1 Hosp Univ Salamanca, Salamanca 37007, Spain. Moorview Hosp, Oxford, England. John Radcliffe Hosp, Oxford OX3 9DU, England. Hosp Prov Nuestra Senora Gracia, Zaragoza, Spain. Fdn Jimenez Diaz, E-28040 Madrid, Spain. Ctr Salud Miguel Armijo, Salamanca, Spain. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. RP Urdaniz, AP (reprint author), Hosp Univ Salamanca, Paseo San Vicente 58-182, Salamanca 37007, Spain. NR 66 TC 2 Z9 2 U1 0 U2 0 PU JUAN JOSE LOPEZ-IBOR FOUNDATION PI MADRID PA NO 2, MADRID, 28035, SPAIN SN 1139-9287 EI 1578-2735 J9 ACTAS ESP PSIQUIATRI JI Actas Esp. Psiquiatri. PD JAN-FEB PY 2001 VL 29 IS 1 BP 47 EP 57 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 431ZA UT WOS:000168660600008 ER PT B AU Titt, U Newhauser, WD Yan, X Dexheimer, DT AF Titt, U Newhauser, WD Yan, X Dexheimer, DT BE Kling, A Barao, F Nakagawa, M Tavora, L Vaz, P TI Neutron shielding calculations for a 230-MeV proton therapy facility SO ADVANCED MONTE CARLO FOR RADIATION PHYSICS, PARTICLE TRANSPORT SIMULATION AND APPLICATIONS LA English DT Proceedings Paper CT International Conference on Advanced Monte Carlo for Radiation Physics, Particle Transport Simulation and Applications CY OCT 23-26, 2000 CL LISBON, PORTUGAL AB Proton radiation therapy is of increasing interest in the treatment of cancer because of its superior outcome in several clinical trials. High energy protons produce unwanted neutrons, which in turn necessitates the protection of patients, staff and the public from neutron exposures. A Monte Carlo method to model the neutron production and shielding at a proton therapy facility is described here. This method can be used to study existing facilities and optimize neutron shielding for future proton centers. C1 Massachusetts Gen Hosp, Boston, MA USA. RP Titt, U (reprint author), Massachusetts Gen Hosp, 55 Fruit St,NPT-100, Boston, MA USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-41795-8 PY 2001 BP 1075 EP 1080 PG 6 WC Physics, Multidisciplinary; Physics, Particles & Fields; Physics, Mathematical SC Physics GA BU24J UT WOS:000175458200173 ER PT J AU Castrillon, DH DePinho, RA AF Castrillon, DH DePinho, RA TI Modeling prostate cancer in the mouse SO ADVANCES IN CANCER RESEARCH, VOL 82 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID TISSUE-SPECIFIC EXPRESSION; CELL-CYCLE PROGRESSION; TUMOR-SUPPRESSOR GENE; RAT VENTRAL PROSTATE; TRANSGENIC MICE; HOMEOBOX GENE; GROWTH-FACTOR; REGULATED EXPRESSION; SIGNALING PATHWAY; SONIC HEDGEHOG C1 Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Genet, Boston, MA 02115 USA. RP Castrillon, DH (reprint author), Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [5U01 CA84313-02, K08 CA84044-03, 9R01 CA86379-08] NR 76 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 2001 VL 82 BP 187 EP 204 DI 10.1016/S0065-230X(01)82006-6 PG 22 WC Oncology SC Oncology GA BS65Z UT WOS:000170766700006 PM 11447763 ER PT J AU Sachs, DH Sykes, M Robson, SC Cooper, DKC AF Sachs, DH Sykes, M Robson, SC Cooper, DKC TI Xenotransplantation SO ADVANCES IN IMMUNOLOGY, VOL 79 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID PORCINE ENDOTHELIAL-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; NATURAL-KILLER-CELLS; ANTI-GAL ANTIBODY; HUMAN T-CELLS; DISCORDANT XENOGRAFT REJECTION; BONE-MARROW CHIMERAS; LONG-TERM SURVIVAL; PIG THYMUS GRAFTS; HUMAN NK CELLS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. NR 554 TC 72 Z9 74 U1 2 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2001 VL 79 BP 129 EP 223 DI 10.1016/S0065-2776(01)79004-9 PG 95 WC Immunology SC Immunology GA BT13E UT WOS:000172043700004 PM 11680007 ER PT B AU Keith, RL Miller, YE Gesell, TL Moore, MD Malkinson, AM Geraci, MW AF Keith, RL Miller, YE Gesell, TL Moore, MD Malkinson, AM Geraci, MW BE Samuelsson, B Paoletti, R Folco, GC Granstrom, E Nicosia, S TI Pulmonary prostacyclin synthase overexpression improves survival following butylated hydroxytoluene exposure SO ADVANCES IN PROSTAGLANDIN AND LEUKOTRIENE RESEARCH: BASIC SCIENCE AND NEW CLINICAL APPLICATIONS SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT 11th International Conference on Advances in Prostaglandin and Leukotriene Research CY JUN 04-08, 2000 CL FLORENCE, ITALY ID LUNG TUMORIGENESIS; TRANSGENIC MICE; A/J MICE C1 Denver VA Med Ctr, Dept Med, Div Pulmonary Sci & Crit Care Med, Denver, CO 80220 USA. RP Keith, RL (reprint author), Denver VA Med Ctr, Dept Med, Div Pulmonary Sci & Crit Care Med, 1055 Clermont St Box 111A, Denver, CO 80220 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-0146-0 J9 MED SCI SYMP SER PY 2001 VL 16 BP 187 EP 190 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU18E UT WOS:000175262600036 ER PT J AU Gardner, MM Buchner, DM Robertson, MC Campbell, AJ AF Gardner, MM Buchner, DM Robertson, MC Campbell, AJ TI Practical implementation of an exercise-based falls prevention programme SO AGE AND AGEING LA English DT Article DE exercise; falls; older people ID RANDOMIZED CONTROLLED TRIAL; ELDERLY PERSONS; OLDER PERSONS; RISK-FACTORS; COMMUNITY; BALANCE; STRENGTH; HEALTH; ADULTS; PEOPLE AB Muscle weakness and impaired balance are risk factors underlying many falls and fall injuries experienced by older people. Fall prevention strategies have included exercise programmes that lower the risk of falling by improving strength and balance. We have developed an individually tailored, home-based, strength and balance retraining programme, which has proven successful in reducing falls and moderate fall injuries in people aged 80 years and older. Here we describe a simple assessment of strength and balance and the content and delivery of a falls prevention exercise programme. C1 Univ Otago, Sch Med, Dept Med & Surg Sci, Dunedin, New Zealand. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Campbell, AJ (reprint author), Univ Otago, Sch Med, Dept Med & Surg Sci, POB 913, Dunedin, New Zealand. RI Robertson, Mary Clare/A-3964-2009 NR 23 TC 93 Z9 94 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD JAN PY 2001 VL 30 IS 1 BP 77 EP 83 DI 10.1093/ageing/30.1.77 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 421QP UT WOS:000168075300017 PM 11322678 ER PT J AU Allen, TM Watkins, DI AF Allen, TM Watkins, DI TI New insights into evaluating effective T-cell responses to HIV SO AIDS LA English DT Article DE HIV; SIV; CTL; T-helper ID SIMIAN IMMUNODEFICIENCY VIRUS; LONG-TERM NONPROGRESSORS; LIVE-ATTENUATED SIV; CTL ESCAPE VIRUS; LYMPHOCYTE-RESPONSES; RHESUS-MONKEYS; PRIMARY INFECTION; PROLIFERATIVE RESPONSES; GENETIC-VARIATION; PERIPHERAL-BLOOD C1 Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. RP Allen, TM (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [R01 AI46366] NR 100 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 2001 VL 15 SU 5 BP S117 EP S126 DI 10.1097/00002030-200100005-00015 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 504AL UT WOS:000172834100015 PM 11816159 ER PT J AU Gottlinger, HG AF Gottlinger, HG TI The HIV-1 assembly machine SO AIDS LA English DT Review DE gag; structure; particle assembly; virus release ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 MATRIX PROTEIN; ROUS-SARCOMA VIRUS; MURINE LEUKEMIA-VIRUS; GP41 CYTOPLASMIC TAIL; PFIZER-MONKEY-VIRUS; PROLINE-RICH MOTIF; CYCLOPHILIN-A; GAG PROTEIN; MEMBRANE-BINDING C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gottlinger, HG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI29873, AI42510, R01 AI042510] NR 115 TC 97 Z9 97 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 2001 VL 15 SU 5 BP S13 EP S20 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 504AL UT WOS:000172834100003 PM 11816161 ER PT J AU Dretler, SP AF Dretler, SP TI Devices to prevent ureteral stone migration during retrograde ureteroscopy SO AKTUELLE UROLOGIE LA German DT Article DE ureteroscopy; lithotripsy; stone migration AB Purpose: Retrograde migration of upper and lower ureteral calculi during ureteroscopy and fragmentation is a common problem during lithotripsy. Herein we present a new device to present this stone migration. Materials and Methods: In 42 patients an 0.038-inch guide wire with a balloon on the distal end ("passport balloon" or "balloon on a wire") was placed beside the safety guide wire, advanced above the impacted stone and expanded to 12F if the ureters were not too dilated. In a second in vitro study, a "stone cone" composed of twisted stainless steel and nitinol with a burned-in memory which springs into the shape of a tapered coil was developed and tested. Results: In 29 out of the 42 patients, the balloon on the wire could be brought above the stone in,ureters which had not been too greatly dilated. In these patients, the balloon prevented proximal fragmentation migration in 86 %. The "stone cone" showed promising results in vitro. In 5 of 6 cases, stone migration was prevented in an artificial ureter. Only the Holium:YAG laser was problematic and could not be used. Conclusions: The balloon on the wire was successful in preventing stone migration in selected patients. To increase the number of suitable patients, the stone cone was developed and tested in vitro with promising results. C1 Massachusetts Gen Hosp, Kidney Stone Ctr, Boston, MA 02114 USA. RP Dretler, SP (reprint author), Care of Stein R, Univ Mainz, Urol Klin & Poliklin, Langenbeckstr 1, D-55131 Mainz, Germany. NR 3 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0001-7868 J9 AKTUEL UROL JI Aktuelle Urol. PD JAN PY 2001 VL 32 IS 1 BP 17 EP 20 DI 10.1055/s-2001-10743 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 402KW UT WOS:000166987000004 ER PT B AU Albert, MS Killiany, RJ Johnson, K Tanzi, R Jones, K AF Albert, MS Killiany, RJ Johnson, K Tanzi, R Jones, K BE Iqbal, K Sisodia, SS Winblad, B TI Preclinical prediction of AD: Relation between neuropsychological and neuroimaging findings SO ALZHEIMER'S DISEASE: ADVANCES IN ETIOLOGY, PATHOGENESIS AND THERAPEUTICS LA English DT Proceedings Paper CT 7th International Conference on Alzheimers Disease and Related Disorders CY JUL, 2000 CL WASHINGTON, D.C. ID CEREBRAL GLUCOSE-METABOLISM; MILD ALZHEIMERS-DISEASE; ENTORHINAL CORTEX; APOLIPOPROTEIN-E; CINGULATE CORTEX; TEMPORAL-LOBE; MEMORY; DEMENTIA; SPECT; DEFICITS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Albert, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH E 149 9124, Charlestown, MA 02129 USA. NR 57 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 0-471-52176-0 PY 2001 BP 99 EP 110 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA BS72F UT WOS:000170986000010 ER PT B AU Growdon, JH AF Growdon, JH BE Iqbal, K Sisodia, SS Winblad, B TI Evaluating CNS biomarkers for Alzheimer's disease SO ALZHEIMER'S DISEASE: ADVANCES IN ETIOLOGY, PATHOGENESIS AND THERAPEUTICS LA English DT Proceedings Paper CT 7th International Conference on Alzheimers Disease and Related Disorders CY JUL, 2000 CL WASHINGTON, D.C. ID AMYLOID BETA-PROTEIN; CYSTATIN-C GENE; CEREBROSPINAL-FLUID; ONSET; AD; POLYMORPHISM; ATROPHY; ASSOCIATION; RISK; CSF C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Growdon, JH (reprint author), Massachusetts Gen Hosp, WACC 830, Boston, MA 02114 USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 0-471-52176-0 PY 2001 BP 265 EP 273 DI 10.1002/0470846453.ch24 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA BS72F UT WOS:000170986000024 ER PT B AU Puglielli, L Ingano, LAM Tanzi, RE Kovacs, DM AF Puglielli, L Ingano, LAM Tanzi, RE Kovacs, DM BE Iqbal, K Sisodia, SS Winblad, B TI The amyloid precursor protein V717I mutation increases susceptibility to cell death in a cholesterol-dependent manner SO ALZHEIMER'S DISEASE: ADVANCES IN ETIOLOGY, PATHOGENESIS AND THERAPEUTICS LA English DT Proceedings Paper CT 7th International Conference on Alzheimers Disease and Related Disorders CY JUL, 2000 CL WASHINGTON, D.C. ID FAMILIAL ALZHEIMERS-DISEASE; HUMAN FIBROBLASTS; PLASMA-MEMBRANE; APOPTOSIS; GENE; GENERATION; NEURONS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Unit,Dept Neurol, Charlestown, MA 02129 USA. RP Puglielli, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Unit,Dept Neurol, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 0-471-52176-0 PY 2001 BP 469 EP 477 DI 10.1002/0470846453.ch42 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA BS72F UT WOS:000170986000042 ER PT B AU Cheng, I Yoo, AS Tanzi, RE Kim, TW AF Cheng, I Yoo, AS Tanzi, RE Kim, TW BE Iqbal, K Sisodia, SS Winblad, B TI Familial Alzheimer's disease-linked mutant presenilins attenuate capacitative calcium entry SO ALZHEIMER'S DISEASE: ADVANCES IN ETIOLOGY, PATHOGENESIS AND THERAPEUTICS LA English DT Proceedings Paper CT 7th International Conference on Alzheimers Disease and Related Disorders CY JUL, 2000 CL WASHINGTON, D.C. ID CA2+ STORES; FIBROBLASTS; CELLS C1 Harvard Univ, Sch Med, Genet & Aging Unit, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Kim, TW (reprint author), Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, 630 W 168th St,P&S14-511, New York, NY 10032 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 0-471-52176-0 PY 2001 BP 515 EP 519 DI 10.1002/0470846453.ch47 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA BS72F UT WOS:000170986000047 ER PT J AU Kim, C Schaaf, CH Maynard, C Every, NR AF Kim, C Schaaf, CH Maynard, C Every, NR TI Unstable angina in the Myocardial Infarction Triage and Intervention Registry (MITI): Short- and long-term outcomes in men and women SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; HEART-DISEASE; BYPASS-SURGERY; SEX; MORTALITY; PROGNOSIS; SURVIVAL; BIAS AB Background studies of unstable angina have focused on hospital mortality; long-term mortality studies have been limited by small numbers of patients or health care providers. The objectives of this study were to determine whether men and women with unstable angina had different presentations, mortality rates, and procedure utilization. Methods We analyzed a prospective observational registry of 4305 men (60%) and 2847 women (40%) with unstable angina who were admitted to coronary care units in King County, Washington, between 1988 and 1994. We compared the rates of symptoms, survival, and procedure utilization between sexes after adjustment for age, race, insurance status, and medical history. Results Women were older and had higher rates of hypertension and congestive heart failure than men bur had lower rates of cigarette smoking, previous myocardial infarction, and previous procedure use (P<.0001). Women had significantly higher rates of dyspnea, nausea, and epigastric pain and less diaphoresis than men did (P<.0001). Women underwent fewer procedures, but after adjustment for age and medical history this difference was no longer significant except for coronary bypass grafting (odds ratio 0.50, 95% confidence interval [CI] 0.37-0.69); after index hospitalization, men and women underwent procedures at similar rates. Although women had higher rehospitalization rates than men, early mortality (odds ratio 0.89, 95% CI 0.55-1.4) and late mortality (hazard ratio 0.98, 95% CI 0.95-1.0) were similar between men and women after adjustment for age. Conclusions Women and men with unstable angina have different risk factors and symptoms upon presentation but have similar procedure use and mortality rates. C1 Univ Washington, Robert Wool Johnson Clin Scholars Program, Seattle, WA 98195 USA. Univ Washington, Dept Nursing, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, NW Hlth Care Serv Res & Dev Program, Dept Med, Div Cardiol, Seattle, WA USA. RP Kim, C (reprint author), Univ Washington, Robert Wool Johnson Clin Scholars Program, Seattle, WA 98195 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 26 TC 17 Z9 17 U1 1 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 JAN PY 2001 VL 141 IS 1 BP 73 EP 77 DI 10.1067/mhj.2001.111546 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 389WR UT WOS:000166262100012 PM 11136489 ER PT J AU Faquin, WC Brown, FM Krane, JF Renshaw, AA Cibas, ES AF Faquin, WC Brown, FM Krane, JF Renshaw, AA Cibas, ES TI Extensively keratinized squamous intraepithelial lesions of the cervix are difficult to grade SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE keratinizing; LSIL; HSIL; grade; squamous intraepithelial lesion; cervical intraepithelial neoplasia; Papanicolaou smear ID HUMAN PAPILLOMAVIRUS TYPE; NEOPLASIA; MANAGEMENT; CYTOLOGY; SMEAR AB We tested the hypothesis that extensively keratinized squamous intraepithelial lesions (SILs) are difficult to grade precisely by identifying 100 Papanicolaou smears with a keratinizing SIL that had been originally judged difficult to grade. Of these, 65 were confirmed as low grade SIL (LSIL) or high-grade SIL (HSIL) on subsequent biopsy. The 65 smears were reviewed independently by 3 cytopathologists who graded each case as LSIL or HSIL (by Bethesda System criteria). The accuracy of the grade was determined by the subsequent biopsy results; accuracy was compared with that of a historic control group of SILs with biopsy follow-up. In the study group, biopsies showed LSIL in 41 cases and HSIL in 24. The mean accuracy for a smear diagnosis of LSIL was 60% for the study group and 92% for the control group. For a smear diagnosis of HSIL, the accuracy was 60% for the study group and 95% for the control group. The overall kappa value for the study group confirmed poor interobserver agreement. Some keratinizing SILs are difficult if not impossible to grade precisely using standard criteria. For such lesions, the diagnosis "SIL, grade cannot be determined due to extensive keratinization " is justified. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 24 TC 4 Z9 5 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2001 VL 115 IS 1 BP 80 EP 84 PG 5 WC Pathology SC Pathology GA 386CH UT WOS:000166042200008 PM 11190810 ER PT J AU Elman, I Karlsgodt, KH Gastfriend, DR AF Elman, I Karlsgodt, KH Gastfriend, DR TI Gender differences in cocaine craving among non-treatment-seeking individuals with cocaine dependence SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE depression; dopamine; estrogen; HRSD; POMS ID SEX-DIFFERENCES; NUCLEUS-ACCUMBENS; ABUSERS; DEPRESSION; HYPERSENSITIVITY; PSYCHOPATHOLOGY; EXPERIENCES; VOLUNTEERS; DISORDERS; ADDICTION AB The purpose of this pilot study was to evaluate potential gender differences in cocaine craving among non-treatment seekers with cocaine dependence. We examined 10 female and Il male individuals matched by demographic characteristics and severity of drug use; we used a multidimensional questionnaire that assesses various aspects of craving: (a) current intensity, (b) projected intensity, (c) resistance to use cocaine, (d) responsiveness to drug-related conditioned stimuli, and (e) imagined likelihood of use if in a setting with access to drugs. Other instruments utilized were the Hamilton Rating Scale for Depression and Addiction Severity Index. Female subjects had hight I total craving scores (p < .05), with post hoc tests showing more present desire to use cocaine and responsivity to drug-conditioned stimuli, along with lower scores on the desire not to use cocaine. In exploratory analyses, we found greater depressive symptomatology (p = .02) and severity of family/social problems (p = .02) in ti males than their males counterparts. These results suggest that gender may influence different aspects of cocaine craving. As estrogen is purported to modulate craving-related dopaminergic systems, further studies will be needed to confirm these observed gender differences and to investigate their possible mechanisms, particularly estrogen-dopamine interactions and their effect on craving and mood. C1 Massachusetts Gen Hosp, Dept Psychiat, Addict Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Elman, I (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Addict Serv, 15 Parkman St,WACC-812, Boston, MA 02114 USA. RI Reis, Aline/G-9573-2012; Karlsgodt, Katherine/H-2964-2013 OI Karlsgodt, Katherine/0000-0003-3332-4231 FU NIDA NIH HHS [DA 00265-01, DA 00275-01, DA 0878] NR 36 TC 85 Z9 90 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2001 VL 27 IS 2 BP 193 EP 202 DI 10.1081/ADA-100103705 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 455BH UT WOS:000170007300002 PM 11417935 ER PT J AU Rosen, CL Brown, DFM Chang, YC Moore, C Averill, NJ Arkoff, LJ McCabe, CJ Wolfe, RE AF Rosen, CL Brown, DFM Chang, YC Moore, C Averill, NJ Arkoff, LJ McCabe, CJ Wolfe, RE TI Ultrasonography by emergency physicians in patients with suspected cholecystitis SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 17-19, 1998 CL CHICAGO, ILLINOIS SP Soc Acad Emergency Med DE bedside; emergency; ultrasonography; cholelithiasis; cholecystitis ID ULTRASOUND; GALLBLADDER; CHOLECYSTOSONOGRAPHY; CHOLECYSTOGRAPHY; DIAGNOSIS; DISEASE; SIGNS AB This article investigates the use of bedside abdominal ultrasonography (BAU) performed by emergency physicians (EPs) to screen patients for cholelithiasis and cholecystitis. In this prospective study EPs performed BAU on 116 patients. Agreement between BAU and formal abdominal ultrasound (FUS) performed in the radiology department for detecting cholelithiasis and cholecystitis was determined using Kappa statistics, Test characteristics of BAU for detecting cholelithiasis and acute cholecystitis were calculated. Agreement between BAU and FUS was 0.71 for cholelithiasis and 0.46 for acute cholecystitis. Test characteristics of BAU for cholelithiasis were sensitivity 92%, specificity 78%, positive predictive value (PPV) 86%, negative predictive value (NPV) 88%. Test characteristics of BAU for acute cholecystitis compared with clinical follow-up were sensitivity 91%, specificity 66%, PPV 70%, NPV 90%, BAU may be used to exclude cholelithiasis and is sensitive for cholecystitis. However, when EPs with limited experience identify cholecystitis a confirmatory test is warranted before cholecystectomy, (Am J Emerg Med 2001;19:32-36. Copyright (C) 2001 by W.B. Saunders Company). C1 Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Rosen, CL (reprint author), Beth Israel Deaconess Med Ctr, Dept Emergency Med, Finard 2,330 Brookline Ave, Boston, MA 02215 USA. NR 24 TC 45 Z9 46 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JAN PY 2001 VL 19 IS 1 BP 32 EP 36 DI 10.1053/ajem.2001.20028 PG 5 WC Emergency Medicine SC Emergency Medicine GA 391UV UT WOS:000166375100008 PM 11146014 ER PT J AU Bennett, JM Young, MS Liesveld, JL Paietta, E Miller, KB Lazarus, HM Marsh, RD Friedenberg, WR Saba, HT Hayes, FA Dewald, GW Hiddemann, W Rowe, JM AF Bennett, JM Young, MS Liesveld, JL Paietta, E Miller, KB Lazarus, HM Marsh, RD Friedenberg, WR Saba, HT Hayes, FA Dewald, GW Hiddemann, W Rowe, JM TI Phase II study of combination human recombinant GM-CSF with intermediate-dose cytarabine and mitoxantrone chemotherapy in patients with high-risk myelodysplastic syndromes (RAEB, RAEBT, and CMML): An Eastern Cooperative Oncology Group study SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE GM-CSF; mitoxantrone; cytarabine; myelodysplastic syndromes ID COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; CLASSIFICATION; PROGNOSIS; CELLS; AGE AB A Phase II study of GM-CSF with intermediate-dose cytarabine and mitoxantrone was conducted in patients with high-risk myelodysplastic syndrome. It was designed to evaluate if priming with growth factor could increase the efficiency of chemotherapy. In this older population only two of 10 patients achieved a bone marrow CR, including one patient whose leukemic blasts had an "S" phase increase of 2.55x at 48 hr. Unexpected hepatotoxicity was noted. This regimen cannot be recommended for this elderly population of patients. (C) 2001 Wiley-Liss, Inc. C1 Univ Rochester, Ctr Canc, Rochester, NY 14642 USA. Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Ctr Stat, Boston, MA USA. Our Lady Mercy Canc Ctr, Bronx, NY USA. Tufts Univ, New England Med Ctr, Sch Med, Boston, MA 02111 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Cleveland, OH 44106 USA. Univ Florida, Ctr Med, Gainesville, FL USA. Marshfield Clin CCOP, Marshfield, WI USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Immunex Corp, Seattle, WA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Mayo Clin, Rochester, MN USA. Univ Munich, Klinikum Grosshadern, Dept Internal Med 3, D-8000 Munich, Germany. Technion Israel Inst Technol, Rambam Med Ctr, Haifa, Israel. RP Bennett, JM (reprint author), Univ Rochester, Ctr Canc, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. FU NCI NIH HHS [CA07190, CA11083, CA23318] NR 26 TC 6 Z9 6 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2001 VL 66 IS 1 BP 23 EP 27 PG 5 WC Hematology SC Hematology GA 384EK UT WOS:000165929300003 PM 11426487 ER PT J AU Lin, AE Liu, Q Mannheim, GB Darras, BT AF Lin, AE Liu, Q Mannheim, GB Darras, BT TI Exclusion of growth factor gene mutations as a common cause of Sotos syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE cerebral gigantism; growth factor; macrocephaly; macrosomia; overgrowth syndromes; Sotos syndrome AB Sotos syndrome is characterized by somatic overgrowth, i.e., macrocephaly and tall stature. Because the cause and pathogenesis of Sotos syndrome remain unknown, we selected nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) as possible genes mutated in Sotos syndrome. In seven patients with the classic phenotype, we excluded mutations in these growth factor genes. It is possible that these three genes are not involved in the cause of Sotos syndrome, or alternatively, mutations could not be identified in the small number of patients studied. Am. J. Med. Gen. 98:101-102, 2001. (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Chongqing Univ Med Sci, Affiliated Hosp 1, Core Lab, Chongqing, Peoples R China. Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Lin, AE (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Warren 801,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 1 PY 2001 VL 98 IS 1 BP 101 EP 102 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 388VE UT WOS:000166203100015 PM 11426446 ER PT J AU Rordorf, G Bellon, RJ Budzik, RF Farkas, J Reinking, GF Pergolizzi, RS Ezzeddine, M Norbash, AM Gonzalez, RG Putman, CM AF Rordorf, G Bellon, RJ Budzik, RF Farkas, J Reinking, GF Pergolizzi, RS Ezzeddine, M Norbash, AM Gonzalez, RG Putman, CM TI Silent thromboembolic events associated with the treatment of unruptured cerebral aneurysms by use of Guglielmi detachable coils: Prospective study applying diffusion-weighted imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT Joint Meeting of the AANS/CNS Section on Cerebrovascular Surgery/American-Society-of-Interventional-and-Therapeutic-Neuroradiolog y CY FEB 06-09, 2000 CL NEW ORLEANS, LOUISIANA SP AANS, CNS, Amer Soc Intervent & Therapeut Neuroradiol ID POSTERIOR CIRCULATION ANEURYSMS; ENDOVASCULAR TREATMENT; INTRACRANIAL ANEURYSMS; SACCULAR ANEURYSMS; ELECTROTHROMBOSIS; EMBOLIZATION; STROKE; EXPERIENCE AB BACKGROUND AND PURPOSE: Aneurysm embolization using Guglielmi detachable coils (GDC) is gaining increasing acceptance as a viable alternative to surgery in the treatment of cerebral aneurysms. Although recent reports describe a significant rate of symptomatic thromboembolic complications with GDC use, many of the neurologic deficits are transient. We sought to determine the incidence of silent thromboembolic events with the use of diffusion-weighted imaging and to correlate radiologic findings with the results of neurologic examinations. METHODS: Diffusion-weighted MR imaging was performed within 48 hours in 14 consecutive elective GDC aneurysm treatments. Embolizations were performed under systemic heparinization; all flush solutions were heparinized, and both guiding catheters and microcatheters were placed for continuous heparinized infusions. Neurologic examination, including the National Institutes of Health Stroke Scale determination, was performed by a stroke neurologist before the coiling procedures were performed, immediately after the procedures were performed, and before discharge. MR imaging examinations were reviewed by a stroke neurologist and an interventional neuroradiologist, with determination and characterization of diffusion-weighted imaging abnormalities. RESULTS: Small areas of restricted diffusion, presumed to represent procedure-related embolic infarctions, were noted on the images of eight of 14 patients. All except one of the areas were located ipsilateral to the side of the catheterization. Six patients had evidence of multiple infarcts. Most lesions were small (<2 mm); one patient with coil stretch and herniation into the parent vessel had numerous infarcts with a dominant posterior frontal infarct, Pre- and post-treatment National Institutes of Health Stroke Scale scores were unchanged for 13 of 14 patients. Overall, the rate of asymptomatic emboli was 61% (eight of 13 treatments) in uncomplicated treatments. Strokes occurred independently of the number of coils used; the mean number of coils used for patients with strokes was 7.6 (range, two to 13) and for patients without evidence of infarcts was 10.2 (range, one to 30), This was not a significant difference (P > .5). CONCLUSION: Silent thromboembolic events related to the use of the GDC system are a common occurrence, despite meticulous technique and systemic anticoagulation, Although clinical sequelae are rare, the high rate of occurrence suggests that alterations in the technique, such as the addition of antiplatelet agents, should be considered. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. RP Rordorf, G (reprint author), Massachusetts Gen Hosp, Dept Neurol, BLK1291,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 111 Z9 113 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2001 VL 22 IS 1 BP 5 EP 10 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 397WK UT WOS:000166720700004 PM 11158880 ER PT J AU Lee, JH Machtay, M McKenna, MG Weinstein, GS Markiewicz, DA Krisch, RE Kligerman, MM AF Lee, JH Machtay, M McKenna, MG Weinstein, GS Markiewicz, DA Krisch, RE Kligerman, MM TI Radiotherapy with 6-megavolt photons for early glottic carcinoma: Potential impact of extension to the posterior vocal cord SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; RADIATION-THERAPY; LOCAL-CONTROL; MULTIVARIATE-ANALYSIS; PROGNOSTIC FACTORS; LARYNGEAL-CANCER; FRACTION SIZE; X-RAYS; T1; T2 AB Purpose: Radiation therapy has a high success rate in the treatment of early glottic carcinoma. Excellent outcomes have been reported from centers using cobalt-60 or relatively low-energy (less than or equal to4 MV) radiation therapy to achieve these results. Whether similar outcomes can be achieved with a 6 MV linear accelerator has been less rigorously evaluated. This study assesses the efficacy of 6 MV radiation therapy for early stage glottic cancer and identifies prognostic factors for local control and overall survival in this common disease. Materials and Methods: One hundred twenty-eight consecutive cases of Tis, T1, and T2 squamous cell carcinomas of the glottis from 1982 to 1996 were retrospectively analyzed with regard to local control and survival. All patients were treated with definitive radiation therapy with a 6-MV linear accelerator. Potential prognostic factors for local control and survival were evaluated with univariate and multivariate models. Median follow-up of locally controlled patients was 65 months. Results: The overall 3-year actuarial local control rates for T1 and T2 carcinomas were 86% and 68%, respectively. Patients with lesions involving the posterior third of the Vocal cord had significantly worse 3-year local control (76% vs. 86%, P = .038). Radiation therapy technique and overall treatment time did not significantly affect local control. For patients with Tis and TI lesions, factors associated with significantly worse local control included cordectomy-ineligible disease (P = .024), dose less than 6,600 cGy (P = .024), and lesions limited to the posterior third of the vocal cord (P = .004). Three-year local control was 76%, with doses less than 6,600 cGy and 90% with higher doses. High rates of second primary malignancies were observed and represented the major cause of death. Five-year overall survival was 84%. Conclusions: The use of 6-MV photons for treatment of early glottic cancer seems to achieve local control similar to that reported with lower-energy photons. However, patients with posterior third involvement had a poorer local control rate with standard radiation therapy, thereby suggesting that alternative approaches be considered. C1 Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA. Delaware Cty Mem Hosp, Dept Radiat Oncol, Drexel Hill, PA USA. Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA USA. RP Machtay, M (reprint author), Hosp Univ Penn, Dept Radiat Oncol, 3400 Spruce St,2 Donner, Philadelphia, PA 19104 USA. NR 46 TC 20 Z9 20 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD JAN-FEB PY 2001 VL 22 IS 1 BP 43 EP 54 DI 10.1053/AJOT.2001.20679 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA 402ME UT WOS:000166991300006 PM 11172214 ER PT J AU Stemmer-Rachamimov, AO Wiederhold, T Nielsen, GP James, M Pinney-Michalowski, D Roy, JE Cohen, WA Ramesh, V Louis, DN AF Stemmer-Rachamimov, AO Wiederhold, T Nielsen, GP James, M Pinney-Michalowski, D Roy, JE Cohen, WA Ramesh, V Louis, DN TI NHE-RF, a merlin-interacting protein, is primarily expressed in luminal epithelia, proliferative endometrium, and estrogen receptor-positive breast carcinomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SIGNALING PATHWAYS; GROWTH-FACTOR; CANCER-CELLS; PDZ DOMAIN; MEMBRANE; ESTRADIOL; PHOSPHORYLATION; CYTOSKELETON; STIMULATION; EXCHANGER AB NHE-RF, a regulatory cofactor for NHE (Na+-H+ exchanger) type 3, interacts with ion transporters and receptors through its PDZ domains and with the MERM proteins (merlin, ezrin, radixin and moesin) via its carboxyl terminus. Thus, NHE-RF may act as a multifunctional adaptor protein and play a role in the assembly of signal transduction complexes, linking ion channels and receptors to the actin cytoskeleton, NHE-RF expression is up-regulated in response to estrogen in estrogen receptor-positive breast carcinoma cell lines, suggesting that it may be involved in estrogen signaling. To further understand NHE-RF function and its possible role in estrogen signaling, we analyzed NHE-RF expression in normal human tissues, including cycling endometrium, and in breast carcinomas, tissues in which estrogen plays an important role in regulating cell growth and proliferation. NHE-RF is expressed in many epithelia, especially in cells specialized in ion transport or absorption, and is often localized to apical (luminal) membranes. NHE-RF expression varies markedly in proliferative versus secretory endometrium, with high expression in proliferative (estrogen-stimulated) endometrium. Furthermore, estrogen receptor status and NHE-RF expression correlate closely in breast carcinoma specimens. These findings support a role for NHE-RF in estrogen signaling. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Mol Neurogenet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, WRN 3,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS24279, P01 NS024279] NR 23 TC 64 Z9 65 U1 0 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2001 VL 158 IS 1 BP 57 EP 62 DI 10.1016/S0002-9440(10)63944-2 PG 6 WC Pathology SC Pathology GA 390XV UT WOS:000166325800009 PM 11141479 ER PT J AU Wynn, AA Miyakawa, K Miyata, E Dranoff, G Takeya, M Takahashi, K AF Wynn, AA Miyakawa, K Miyata, E Dranoff, G Takeya, M Takahashi, K TI Role of granulocyte/macrophage colony-stimulating factor in zymocel-induced hepatic granuloma formation SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; FACTOR-DEFICIENT MICE; MACROPHAGE PRECURSOR CHARACTERIZATION; HUMAN-ENDOTHELIAL CELLS; GM-CSF; MONOCLONAL-ANTIBODY; DENDRITIC CELLS; MESSENGER-RNA; BETA-GLUCAN; HEMATOPOIETIC-CELLS AB To examine the role of granulocyte/macrophage colony-stimulating factor (GM-CSF) in inflammatory granuloma formation, we injected GM-CSF-deficient (GM-CSF-/-) mice and wild-type (GM-CSF+/+) mice intravenously with 2 mg of zymocel, and mice were killed at various intervals for examination. In GM-CSF-/- mice, we demonstrated a marked delay of zymocel-induced hepatic granuloma formation until 5 days after zymocel injection with a rapid reduction in numbers of granulomas at 10 days until their disappearance. In the early phase of granuloma formation, monocyte infiltration and differentiation of monocytes into macrophages were impaired in GM-CSF-/- mice compared with GM-CSF+/+ mice. The percentages of [H-3]thymidine-labeled macrophages at 2 days after zymocel injection were lower in the GM-CSF-/- mice than in the GM-CSF+/+ mice. The DNA nick-end-labeling method demonstrated increased numbers of apoptotic cells in and around hepatic granulomas of GM-CSF-/- mice from 8 days after zymocel injection, and electron microscopy detected apoptotic bodies. Granuloma macrophage digestion of glucan particles and activation of macrophages were similar in the two types of mice. In situ hybridization demonstrated expression of GM-CSF mRNA in the endothelial cells, hepatocytes, and some granuloma cells in the GM-CSF+/+ mice but not in the GM-CSF-/- mice. These results provide evidence that GM-CSF is important for the influx of monocytes into hepatic granulomas, for differentiation of monocytes into macrophages, and for proliferation and survival of macrophages within hepatic granulomas. C1 Kumamoto Univ, Sch Med, Dept Pathol 2, Kumamoto 8600811, Japan. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Takahashi, K (reprint author), Kumamoto Univ, Sch Med, Dept Pathol 2, 2-2-1 Honjo, Kumamoto 8600811, Japan. NR 77 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2001 VL 158 IS 1 BP 131 EP 145 DI 10.1016/S0002-9440(10)63951-X PG 15 WC Pathology SC Pathology GA 390XV UT WOS:000166325800016 PM 11141486 ER PT J AU Joussen, AM Murata, T Tsujikawa, A Kirchhof, B Bursell, SE Adamis, AP AF Joussen, AM Murata, T Tsujikawa, A Kirchhof, B Bursell, SE Adamis, AP TI Leukocyte-mediated endothelial cell injury and death in the diabetic retina SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ADHESION MOLECULE-1; P-SELECTIN; RETINOPATHY; INHIBITION; NEOVASCULARIZATION AB Endothelial cell death is a hallmark of diabetic retinopathy. Its occurrence is required for the formation of acellular (devitalized) capillaries, lesions that produce irreversible retinal ischemia through their inability to support blood now. The mechanisms underlying diabetic retinal endothelial cell injury and death remain largely unknown. The current study demonstrates that adherent leukocytes are temporally and spatially associated with retinal endothelial cell injury and death within 1 week of streptozotocin-induced experimental diabetes in rats. Moreover, the antibody-based neutralization of intercellular adhesion molecule-1 and CD18 is shown to prevent both leukocyte adhesion and retinal endothelial cell injury and death. These data highlight the central and causal role of adherent leukocytes in the pathogenesis of diabetic retinopathy. They also underscore the potential utility of anti-intercellular adhesion molecule1- and anti-CD18-based therapies in the treatment of diabetic retinopathy, a newly recognized inflammatory disease. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab, Boston, MA 02115 USA. Rhein Westfal TH Aachen, Dept Ophthalmol, D-5100 Aachen, Germany. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY12611, EY11627] NR 15 TC 300 Z9 335 U1 2 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2001 VL 158 IS 1 BP 147 EP 152 DI 10.1016/S0002-9440(10)63952-1 PG 6 WC Pathology SC Pathology GA 390XV UT WOS:000166325800017 PM 11141487 ER PT J AU Irizarry, MC Locascio, JJ Hyman, BT AF Irizarry, MC Locascio, JJ Hyman, BT TI beta-site APP cleaving enzyme mRNA expression in APP transgenic mice - Anatomical overlap with transgene expression and static levels with aging SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; MESSENGER-RNA; SECRETASE ACTIVITY; NEURONAL LOSS; PRESENILIN-1; DEPOSITION; MOUSE; BRAIN; PATHOLOGY AB The principal enzyme responsible for the beta -site cleavage of amyloid precursor protein (APP) in the brain is a membrane-bound aspartyl protease beta -site APP cleaving enzyme (BACE). We examined human APP (hAPP) and BACE mRNA expression by in situ hybridization in young and old hAPP transgenic mice from two lines: Tg2576, hAPP KM670-671NL (hAPP(Sw)) at 4 and 15 months; and PDAPP, hAPP V717F, at 4 and 11 months. In transgene-positive mice from both lines, hAPP expression was most prominent in cortical, cerebellar, and hippocampal neuronal populations. Cingulate, entorhinal, and hippocampal amyloid burden in transgene-positive 16-month Tg2576 mice was 4 to 8%, and in 12-month PDAPP mice, 2 to 4%; there was no cerebellar amyloid deposition BACE expression in transgenic and nontransgenic mice was highest in the cerebellar granule cell layer and hippocampal neuronal layers, intermediate in cortex, lower in subcortical regions, and minimal or absent in white matter of the cerebellum. Emulsion-dipped sections confirmed a predominantly neuronal pattern of expression. The amount of hybridization signal did not differ between transgenic and nontransgenic mice, or young and old mice, within each line. Thus, hAPP and endogenous BACE expression in similar anatomical localizations allow for processing of hAPP and A beta formation in hAPP transgenic mice, but these are modified by additional age-related and anatomical factors. C1 Massachusetts Gen Hosp, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimers Dis Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [P50 AG005134, AG05134, AG00793] NR 31 TC 50 Z9 50 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2001 VL 158 IS 1 BP 173 EP 177 DI 10.1016/S0002-9440(10)63955-7 PG 5 WC Pathology SC Pathology GA 390XV UT WOS:000166325800020 PM 11141490 ER PT J AU Li, QL Jansen, E Brent, GA Friedman, TC AF Li, QL Jansen, E Brent, GA Friedman, TC TI Regulation of prohormone convertase 1 (PC1) by thyroid hormone SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE posttranslational processing; negative thyroid response element; hypothyroidism; processing enzyme; pituitary; regulation; triiodo-L-thyronine ID VASOACTIVE INTESTINAL PEPTIDE; CAMP RESPONSE ELEMENTS; RETINOID-X-RECEPTOR; ANTERIOR-PITUITARY; PROMOTER ACTIVITY; NEUROENDOCRINE TISSUES; NEGATIVE REGULATION; RAT PITUITARY; DNA-BINDING; HALF-SITES AB The prohormone convertases (PCs) PC1 and PC2 are key enzymes capable of processing a variety of prohormones to their bioactive forms. In this study, we demonstrated that 6-n-propyl-2-thiouracil (PTU)-induced hypothyroidism stimulated, whereas triido-L-thyronine (T-3)-induced hyperthyroidism suppressed, PC1 mRNA levels in the rat anterior pituitary. Using 5' deletions of the human PC1 (hPC1) promoter transiently transfected into GH3 (a somatotroph cell line) cells, we found that T-3 negatively regulated hPC1 promoter activity and that this regulation required the region from -82 to +19 bp relative to the transcription start site. Electrophoretic mobility shift assays (EMSAs) using purified thyroid hormone receptor-alpha1 (TR alpha1) and retinoid X receptor-beta (RXR beta) proteins and GH3 nuclear extracts demonstrated that the region from -10 to +19 bp of the hPC1 promoter bound TR alpha1 as both a monomer and a homodimer and bound TR alpha1/RXR beta as a heterodimer and multimer. EMSAs with oligonucleotides containing point mutations of the putative negative thyroid response elements (TREs) exhibited diminished homodimer and loss of multimer binding. We conclude that there are multiple novel TRE-like sequences in the hPC1 promoter located from -10 to +19 bp. C1 Charles R Drew Univ Med & Sci, Univ Calif Los Angeles, Sch Med, Div Endocrinol, Los Angeles, CA 90059 USA. Univ Calif Los Angeles, Sch Med, Cedars Sinai Res Inst, Dept Med,Div Endocrinol, Los Angeles, CA 90048 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Div Endocrinol, Los Angeles, CA 90073 USA. Katholieke Univ Leuven, Ctr Human Genet, Mol Oncol Lab, B-3000 Louvain, Belgium. Flanders Interuniv Inst Biotechnol, B-3000 Louvain, Belgium. RP Charles R Drew Univ Med & Sci, Univ Calif Los Angeles, Sch Med, Div Endocrinol, 1721 E 120th St, Los Angeles, CA 90059 USA. EM Friedmant@hotmail.com FU NIDA NIH HHS [DA-00276]; NIDDK NIH HHS [DK-43714, DK-287235] NR 54 TC 23 Z9 23 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2001 VL 280 IS 1 BP E160 EP E170 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 383WZ UT WOS:000165908800019 PM 11120670 ER PT J AU Tsuruoka, S Swenson, ER Petrovic, S Fujimura, A Schwartz, GJ AF Tsuruoka, S Swenson, ER Petrovic, S Fujimura, A Schwartz, GJ TI Role of basolateral carbonic anhydrase in proximal tubular fluid and bicarbonate absorption SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE in vitro microperfusion; acidification; cell pH; inulin; dextran; para-fluorobenzyl-aminobenzolamide; hydratase assay ID MEDULLARY COLLECTING DUCT; II-DEFICIENT MICE; MEMBRANE-VESICLES; RENAL CORTEX; NA+-HCO3 COTRANSPORT; CONVOLUTED TUBULES; STRAIGHT TUBULE; TRANSPORT; KIDNEY; CELLS AB Membrane-bound carbonic anhydrase (CA) is critical to renal acidification. The role of CA activity on the basolateral membrane of the proximal tubule has not been defined clearly. To investigate this issue in microperfused rabbit proximal straight tubules in vitro, we measured fluid and HCO(3)(-) absorption and cell pH before and after the extracellular CA inhibitor p-fluorobenzyl-aminobenzolamide was applied in the bath to inhibit only basolateral CA. This inhibitor was 1% as permeant as acetazolamide. Neutral dextran (2 g/dl, molecular mass 70,000) was used as a colloid to support fluid absorption because albumin could affect CO(2) diffusion and rheogenic HCO(3)(-) efflux. Indeed, dextran in the bath stimulated fluid absorption by 55% over albumin. Basolateral CA inhibition reduced fluid absorption (similar to 30%) and markedly decreased HCO(3)(-) absorption (similar to 60%), both reversible when CA was added to the bathing solution. In the presence of luminal CA inhibition, which reduced fluid (similar to 16%) and HCO(3)(-) (similar to 66%) absorption, inhibition of basolateral CA further decreased the absorption of fluid (to 74% of baseline) and HCO(3)(-) (to 22% of baseline). CA inhibition also alkalinized cell pH by similar to0.2 units, suggesting the presence of an alkaline disequilibrium pH in the interspace, which would secondarily block HCO(3)(-) exit from the cell and thereby decrease luminal proton secretion (HCO(3)(-) absorption). These data clearly indicate that basolateral CA has an important role in mediating fluid and especially HCO(3)(-) absorption in the proximal straight tubule. C1 Univ Rochester, Sch Med, Div Nephrol, Dept Pediat, Rochester, NY 14642 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA 98108 USA. Jichi Med Sch, Dept Clin Pharmacol, Kawachi, Tochigi 3290498, Japan. RP Schwartz, GJ (reprint author), Univ Rochester, Sch Med, Div Nephrol, Dept Pediat, Box 777,601 Elmwood Ave, Rochester, NY 14642 USA. EM george_schwartz@urmc.rochester.edu FU NHLBI NIH HHS [HL-45571]; NIDDK NIH HHS [DK-50603] NR 45 TC 39 Z9 39 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2001 VL 280 IS 1 BP F146 EP F154 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 385JA UT WOS:000165999300016 PM 11133524 ER PT J AU Armstrong, K Berlin, M Schwartz, JS Propert, K Ubel, PA AF Armstrong, K Berlin, M Schwartz, JS Propert, K Ubel, PA TI Barriers to influenza immunization in a low-income urban population SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE influenza; patient compliance; socioeconomic factors; immunization ID HEALTH BELIEF MODEL; AFRICAN-AMERICANS; CONTROLLED TRIAL; ELDERLY PERSONS; VACCINATION; ACCEPTANCE; RISK; EFFICACY; BEHAVIOR; WORKERS AB Background: Athough influenza immunization significantly reduces mortality from influenza, over one third of elderly Americans are not immunized each year. Low rates of immunization are particularly concerning among African-American low-income populations. Preliminary interviews suggested that fear of undisclosed ingredients in the influenza vaccine may impede vaccine acceptance in this vulnerable population. Objectives: To assess the role of concern about vaccine contents and other factors in the use of influenza immunization among a predominantly African-American low-income urban population. Methods: Cross-sectional, health-system-population-based, telephone survey of a random sample of West Philadelphia residents aged greater than or equal to 65 years. Results: Of 659 eligible individuals, 486 (73.8%) were successfully interviewed. Concern about undisclosed shot contents was reported by 132 (20%) respondents and was inversely associated with vaccine receipt (OR 0.49, 95% CI 0.26-0.91). This association was similar among African Americans and Caucasians. In addition, receipt of influenza vaccine was inversely associated with belief that immunization is inconvenient (OR 0.14, 95% CI 0.05-0.36), belief that immunization is painful (OR 0.21, 95% CI 0.08-0.54), and history of previous side effects (OR 0.33, 95% CI 0.18-0.60), and positively associated with physician recommendation (OR 3.22, 95% CI 1.76-5.93). Conclusions: In a low-income urban population, concern about undisclosed vaccine contents appears to impede acceptance of influenza immunization among both African Americans and Caucasians. Directly addressing this concern offers a new approach to increasing immunization in this vulnerable population. (C) 2001 American Journal of Preventive Medicine. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 41 TC 91 Z9 91 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2001 VL 20 IS 1 BP 21 EP 25 DI 10.1016/S0749-3797(00)00263-4 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 391LD UT WOS:000166356700004 PM 11137770 ER PT J AU Emmons, KM Rollnick, S AF Emmons, KM Rollnick, S TI Motivational interviewing in health care settings - Opportunities and limitations SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE behavior; community health services; health behavior; health services; interviews; public health ID SMOKING CESSATION INTERVENTION; RANDOMIZED TRIAL; NEGOTIATING SKILLS; PROBLEM DRINKERS; CLINICAL METHOD; HARM REDUCTION; DIABETES CARE; INNOVATION; SMOKERS; MODEL AB Motivational interviewing (MI) has been well studied in specialist settings. There has been considerable interest in applying MI to community health care settings. Such settings represent a significant departure from the more traditional, specialist settings in which MI has been developed and tested. The purpose of this paper is to provide a brief overview of MI and to identify and discuss the key issues that are likely to arise when adapting this approach to health care and public health settings. This paper provides an overview of important issues to consider in adapting an effective counseling strategy to new settings, and is intended to begin a dialogue about the use of MI in community health care settings. (C) 2001 American Journal of Preventive Medicine. C1 Harvard Univ, Ctr Community Based Res, Dana Farber Canc Inst, Sch Publ Hlth,Dept Adult Oncol,Dept Hlth & Social, Boston, MA 02115 USA. Univ Wales Coll Med, Dept Gen Practice, Cardiff CF4 4XN, S Glam, Wales. RP Emmons, KM (reprint author), Harvard Univ, Ctr Community Based Res, Dana Farber Canc Inst, Sch Publ Hlth,Dept Adult Oncol,Dept Hlth & Social, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA73242-04] NR 40 TC 260 Z9 265 U1 8 U2 59 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2001 VL 20 IS 1 BP 68 EP 74 DI 10.1016/S0749-3797(00)00254-3 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 391LD UT WOS:000166356700011 PM 11137778 ER PT J AU Beahrs, JO Gutheil, TG AF Beahrs, JO Gutheil, TG TI Informed consent in psychotherapy SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Academy-of-Psychiatry-and-the-Law CY OCT 22-25, 1998 CL NEW ORLEANS, LA SP Amer Acad Psychiat & Law ID MEMORY; MALPRACTICE; UNCERTAINTY; IMPACT; LEGAL; LAW AB Objective: The authors sought a rational approach to implementing informed consent within the practice of psychotherapy. Method: The history of informed consent in psychotherapy was reviewed to define a common synthesis that maximizes the potential benefits and minimizes the potential hazards. Results: The benefits of informed consent in psychotherapy include fostering a positive treatment outcome through enhancing patient autonomy, responsibility, and self-therapeutic activity; lessening the risks of regressive effects and therapist liability; and helping the practice of psychotherapy extend beyond particular parochialisms by providing checks and balances on therapist judgments. The hazards include the unpredictability of interactional outcomes and the possibilities of replacing positive expectancy with negative suggestion, replacing a therapeutic alliance with a legalistic stance, and misimplying that patients are passive recipients. Conclusions: Practical implementation of informed consent in psychotherapy must balance such tensions in service of optimal treatment. As a guiding principle, the authors recommend that psychotherapists convey to a prospective patient information that is material to the particular patient's decision. The level of detail needed in informed consent discussions varies directly With the cost and risks of the proposed treatment, the presence of viable alternatives and their relative grounding in scientific data and professional acceptance, and the presence of significant controversy. Unresolved is the question of how to address problematic or controversial psychotherapeutic trends that temporarily enjoy wide professional support. C1 Portland VA Med Ctr, Vancouver Div, Portland, OR 97207 USA. RP Beahrs, JO (reprint author), Portland VA Med Ctr, Vancouver Div, V3MHC,POB 1035, Portland, OR 97207 USA. EM beahrs.john_o@portland.va.gov NR 56 TC 41 Z9 45 U1 1 U2 8 PU AMER PSYCHIATRIC PUBLISHING, 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 JAN PY 2001 VL 158 IS 1 BP 4 EP 10 DI 10.1176/appi.ajp.158.1.4 PG 7 WC Psychiatry SC Psychiatry GA 387ZY UT WOS:000166154000002 PM 11136625 ER PT J AU Biederman, J Faraone, SV Hirshfeld-Becker, DR Friedman, D Robin, JA Rosenbaum, JF AF Biederman, J Faraone, SV Hirshfeld-Becker, DR Friedman, D Robin, JA Rosenbaum, JF TI Patterns of psychopathology and dysfunction in high-risk children of parents with panic disorder and major depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GENERALIZED ANXIETY DISORDER; EARLY SEPARATION ANXIETY; DIRECT-INTERVIEW FAMILY; SOCIAL PHOBIA; PSYCHIATRIC-DISORDERS; CO-MORBIDITY; AGORAPHOBIA; ADOLESCENTS; COMORBIDITY; ASSOCIATION AB Objective: The purpose of the study was to evaluate 1) whether an underlying familial predisposition is shared by all anxiety disorders or whether specific risks are associated with specific disorders, and 2) whether panic disorder and major depression have a familial link. Method: The study compared four groups of children: 1) offspring of parents with panic disorder and comorbid major depression (N = 179), 2) offspring of parents with panic disorder without comorbid major depression (N = 29), 3) offspring of parents with major depression without comorbid panic disorder (N = 59), and 4) offspring of parents with neither panic disorder nor major depression (N = 113). Results: Parental panic disorder, regardless of comorbidity with major depression, was associated with an increased risk for panic disorder and agoraphobia in offspring. Parental major depression, regardless of comorbidity with panic disorder, was associated with increased risks for social phobia, major depression, disruptive behavior disorders, and poorer social functioning in offspring. Both parental panic disorder and parental major depression, individually or comorbidly, were associated with increased risk for separation anxiety disorder and multiple (two or more) anxiety disorders in offspring. Conclusions: These findings confirm and extend previous results documenting significant associations between the presence of panic disorder and major depression in parents and patterns of psychopathology and dysfunction in their off sp ri ng. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, WACC 725,15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH47077] NR 49 TC 140 Z9 143 U1 3 U2 25 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2001 VL 158 IS 1 BP 49 EP 57 DI 10.1176/appi.ajp.158.1.49 PG 9 WC Psychiatry SC Psychiatry GA 387ZY UT WOS:000166154000010 PM 11136633 ER PT J AU Henin, A Savage, CR Rauch, SL Deckersbach, T Wilhelm, S Baer, L Otto, MW Jenike, MA AF Henin, A Savage, CR Rauch, SL Deckersbach, T Wilhelm, S Baer, L Otto, MW Jenike, MA TI Is age at symptom onset associated with severity of memory impairment in adults with obsessive-compulsive disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Age at onset is a potentially important marker for neurobiological features of obsessive-compulsive disorder (OCD). This study examined the relationship between age at symptom onset and memory impairment in adults with OCD. Method: The authors used the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test to compare memory functioning of 37 adult OCD patients with self-reported childhood onset of symptoms (onset at less than 18 years of age) with that of 31 patients with adult-onset symptoms. Results: No differences were found between the two groups on any of the verbal and nonverbal memory measures. Conclusions: Self-reported age at symptom onset is not associated with memory performance in adult patients with OCD according to tests previously found to be sensitive to frontal-striatal system dysfunction and impairment in OCD. Such dysfunction appears to be a consistent feature of OCD in adults, regardless of age at initial symptom onset. C1 Massachusetts Gen Hosp, Cognit Neurosci Grp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Savage, CR (reprint author), Massachusetts Gen Hosp, Cognit Neurosci Grp, Dept Psychiat, 149-9102,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH01230] NR 11 TC 20 Z9 23 U1 2 U2 5 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2001 VL 158 IS 1 BP 137 EP 139 DI 10.1176/appi.ajp.158.1.137 PG 3 WC Psychiatry SC Psychiatry GA 387ZY UT WOS:000166154000026 PM 11136649 ER PT J AU Goode, ML Fink, JB Dhand, R Tobin, MJ AF Goode, ML Fink, JB Dhand, R Tobin, MJ TI Improvement in aerosol delivery with helium-oxygen mixtures during mechanical ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID METERED-DOSE INHALER; ACUTE SEVERE ASTHMA; OBSTRUCTIVE PULMONARY-DISEASE; EXPIRATORY FLOW; IN-VITRO; DEPOSITION; THERAPY; MODEL; AIR; BRONCHODILATOR AB In mechanically ventilated patients with airway obstruction, helium-oxygen (He-O-2 mixtures reduce airway resistance and improve ventilation, but their influence on aerosol delivery is unknown. Accordingly, we determined the effect of various He-O-2 mixtures on albuterol delivery from metered-dose inhalers (MDIs) and jet nebulizers in an in vitro model of mechanical ventilation. Albuterol delivery from a MDI was increased when the ventilator circuit contained 80% helium and 20% oxygen (He-O-2 80/20) versus O-2: 46.7 +/- 3.3 versus 30.2 +/- 1.3 (SE)% of the nominal dose (p < 0.001)-the difference was mainly due to decreased drug deposition in the spacer chamber, mean 39.2% and 55.2%, respectively (p < 0.001). Nebulizer efficiency at a flow rate of 6 L/min was five times lower with He-O-2 80/20 than O-2, and the amount of nebulized drug was inversely correlated with gas density (r = 0.94, p < 0.0001). When the nebulizer was operated with O-2, greater albuterol delivery was achieved when the ventilator circuit contained He-O-2 rather than O-2. In summary, He-O-2 mixtures in the circuit increased aerosol delivery for both MDIs and nebulizers in the mechanically ventilated model by as much as 50%. In conclusion, at appropriate flow rates and concentrations, He-O-2 in the ventilator circuit may improve aerosol delivery in mechanically ventilated patients with severe airway obstruction. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med 111 N, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Hines, IL USA. RP Dhand, R (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med 111 N, 5th Ave & Roosevelt Rd, Hines, IL 60141 USA. NR 32 TC 59 Z9 60 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN PY 2001 VL 163 IS 1 BP 109 EP 114 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 394TV UT WOS:000166540100023 PM 11208634 ER PT J AU Matute-Bello, G Frevert, CW Kajikawa, O Skerrett, SJ Goodman, RB Park, DR Martin, TR AF Matute-Bello, G Frevert, CW Kajikawa, O Skerrett, SJ Goodman, RB Park, DR Martin, TR TI Septic shock and acute lung injury in rabbits with peritonitis - Failure of the neutrophil response to localized infection SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; TUMOR-NECROSIS-FACTOR; SEVERE SEPSIS; INFLAMMATORY RESPONSE; MULTICENTER TRIAL; FUSION PROTEIN; COLI PNEUMONIA; CANINE MODEL; BACTEREMIA; COMPARTMENTALIZATION AB The major goal of this study was to investigate the mechanisms that link the host response to a local infection in the peritoneal cavity with the development of sepsis and lung injury. Rabbits were infected by intraperitoneal inoculation of fibrin clots containing Es-cherichia coil at 10(8), 10(9), or 10(10) cfu/clot. Physiologic, bacteriologic, and inflammatory responses were monitored, and the lungs were examined postmortem. At a dose of 108 cfu/clot the animals had resolving infection, and a dose of 109 cfu/clot resulted in persistent infection at 24 h, with minimal systemic manifestations. In contrast, inoculation of 10(10) cfu/clot resulted in rapidly lethal local infection, with septic shock and lung injury. The onset of septic shock was associated with a paradoxical lack of identifiable polymorphonuclear leukocytes (PMN; neutrophils) in the peritoneal cavity. The absence of PMN in the peritoneum was due in part to lysis of intraperitoneal PMN, because the peritoneal fluids contained free myeloperoxidase and induced rapid death of normal rabbit PMN in vitro. Although most animals became bacteremic, only those with a severe systemic inflammation response developed lung injury. These data show that control of an infection in the first compartment in which bacteria enter the host is a critical determinant of the systemic response. Above a threshold dose of bacteria, failure of the local neutrophil response is a key mechanism associated with deleterious systemic responses. Bacteremia alone is not sufficient to cause lung injury. Lung injury occurs only in the setting of a severe systemic inflammatory response and an inadequate leukocyte response at the primary site of infection. C1 Univ Washington, Med Res Serv, Vet Affairs Puget Sound Hlth Care Syst, Sch Med, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Martin, TR (reprint author), Vet Adm Med Ctr, 151L,1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL30542]; NIAID NIH HHS [AI 29103]; NIGMS NIH HHS [GM 37696] NR 34 TC 49 Z9 52 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN PY 2001 VL 163 IS 1 BP 234 EP 243 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 394TV UT WOS:000166540100040 PM 11208651 ER PT J AU Smith, JJ Berlin, L AF Smith, JJ Berlin, L TI Signing a colleague's radiology report SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Rush N Shore Med Ctr, Dept Radiol, Skokie, IL 60076 USA. Rush Med Coll, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Berlin, L (reprint author), Rush N Shore Med Ctr, Dept Radiol, 9600 Gross Point Rd, Skokie, IL 60076 USA. NR 8 TC 7 Z9 8 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 JAN PY 2001 VL 176 IS 1 BP 27 EP 30 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 386QX UT WOS:000166074000005 PM 11133532 ER PT J AU Mullins, ME Kircher, MF Ryan, DP Doody, D Mullins, TC Rhea, JT Novelline, RA AF Mullins, ME Kircher, MF Ryan, DP Doody, D Mullins, TC Rhea, JT Novelline, RA TI Evaluation of suspected appendicitis in children using limited helical CT and colonic contrast material SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society CY MAY 08, 2000 CL WASHINGTON, D.C. SP Amer Roentgen Ray Soc ID COMPUTED-TOMOGRAPHY; DIAGNOSIS; ULTRASONOGRAPHY; APPENDECTOMY; PERFORATION; APPEARANCE; MANAGEMENT; CHILDHOOD; EMERGENCY; US AB OBJECTIVE. Colonic contrast material evaluation of suspected appendicitis in pediatric patients is technically more challenging than in adults because less intraabdominal fat is present. To determine the accuracy and feasibility of focused CT for pediatric patients, we carried out this retrospective investigation. MATERIALS AND METHODS. Between November 1995 and July 1999, 199 pediatric patients (1-18 years old; mean age, 12 years) were examined with focused CT in the emergency division for suspected appendicitis. The findings on CT were compared with the findings at surgery, pathology, and clinical follow-up. RESULTS. There were 64 true-positive CT scans, two false-negative, 128 true-negative, one false-positive, and four indeterminate. Seventy-four patients underwent appendectomy, with a negative appendectomy rate of 9%. One hundred twenty-five patients without appendicitis were treated nonoperatively. The true-positive rate was 32%, true-negative rate was 64%, sensitivity was 97%, specificity was 99%, positive predictive value was 98%, negative predictive value was 98%, and overall accuracy was 96%. Pediatric patients tolerated the procedure well. Colonic contrast material saved time and provided improved identification of the cecum and appendix. In 62 patients without appendicitis, focused CT provided alternative diagnoses. CONCLUSION. Focused CT appears to be nearly as accurate in pediatric patients as in adults. Focused CT provided alternative diagnoses in 48% of the patients for whom CT findings were negative for appendicitis. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Mullins, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders House,55 Fruit St, Boston, MA 02114 USA. NR 36 TC 45 Z9 47 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 JAN PY 2001 VL 176 IS 1 BP 37 EP 41 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 386QX UT WOS:000166074000007 PM 11133535 ER PT J AU Rasheed, AA Deshpande, V Slanetz, PJ AF Rasheed, AA Deshpande, V Slanetz, PJ TI Radiologic-pathologic conferences of the Massachusetts General Hospital - Colonic perforation by ingested chicken bone SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID FISTULA C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Slanetz, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St, Boston, MA 02114 USA. NR 7 TC 5 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 JAN PY 2001 VL 176 IS 1 BP 152 EP 152 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 386QX UT WOS:000166074000027 PM 11133556 ER PT J AU King, R Googe, PB Weilbaecher, KN Mihm, MC Fisher, DE AF King, R Googe, PB Weilbaecher, KN Mihm, MC Fisher, DE TI Microphthalmia transcription factor expression in cutaneous benign, malignant melanocytic, and nonmelanocytic tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE microphthalmia gene; Mitf antibody; melanocytic lesions; immunohistochemistry; melanoma ID CELL SUGAR TUMOR; WAARDENBURG SYNDROME; S-100 PROTEIN; GENE-PRODUCT; SPINDLE-CELL; BETA-CATENIN; MELANOMA; ANGIOMYOLIPOMA; MUTATIONS; HMB-45 AB The protein encoded by the microphthalmia (mi) gene is a transcription factor essential for the development and survival of melanocytes. Using a monoclonal antibody generated against human Mi transcription factor protein (Mitf) the authors previously demonstrated that Mitf expression is conserved in primary and metastatic malignant melanomas, and appears to be a highly sensitive and specific melanocytic marker. Mitf expression in various cutaneous nevi and cutaneous nonmelanocytic tumors has not been documented systematically. The authors evaluated Mitf immunostaining in 62 benign nevi, 58 primary cutaneous melanomas, and 53 nonmelanocytic tumors. Mitf immunostaining was conserved in all benign nevi, with Spitz nevi and neurotized nevi demonstrating decreased staining intensity. With the exception of desmoplastic melanomas, all primary cutaneous melanomas were immunopositive regardless of the cell type. Only one of 14 desmoplastic melanomas was Mitf positive. None of the nonmelanocytic tumors was immunopositive, including those lesions that may resemble melanoma histologically (spindle cell carcinomas, atypical fibroxanthomas, and leiomyosarcomas). The results demonstrate that Mitf antibody expression is conserved in the majority of benign and malignant melanocytic lesions, and that it may be helpful in the diagnosis of primary melanocytic skin lesions. Its use in desmoplastic melanomas is limited and is reflective of other melanocyte-associated antigens. Mitf discriminates between spindle cell nonmelanocytic tumors and melanomas with a spindle cell morphology, and is useful in a panel with other appropriate antibodies. C1 Knoxville Dermatopathol Lab, Knoxville, TN 37922 USA. Univ Tennessee, Dept Pathol, Knoxville, TN USA. Vanderbilt Univ, Dept Pathol, Nashville, TN USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA USA. RP King, R (reprint author), Knoxville Dermatopathol Lab, Suite 23E,6311 Kingston Pike, Knoxville, TN 37922 USA. NR 43 TC 102 Z9 102 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2001 VL 25 IS 1 BP 51 EP 57 DI 10.1097/00000478-200101000-00005 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 384GH UT WOS:000165934100005 PM 11145251 ER PT J AU Cibas, ES Goss, GA Kulke, MH Demetri, GD Fletcher, CDM AF Cibas, ES Goss, GA Kulke, MH Demetri, GD Fletcher, CDM TI Malignant epithelioid angiomyolipoma ('Sarcoma ex angiomyolipoma') of the kidney - A case report and review of the literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE angiomyolipoma; kidney; malignant; epithelioid; immunohistochemistry; metastasis; fine needle aspiration; cytology; doxorubicin ID RENAL ANGIOMYOLIPOMA; TUBEROUS SCLEROSIS; HEPATIC ANGIOMYOLIPOMA; TRANSFORMATION; HMB-45; COMPONENT; VARIANTS; TUMORS AB Malignant epithelioid angiomyolipoma is a recently described rare tumor of the kidney. Its existence has been questioned, however, on the basis of incomplete evidence of malignant behavior, the absence of an associated classic angiomyolipoma component, or the absence of immunoreactivity for HMB-45 in some cases. We describe a case that was HMB-45-positive and arose in association with a classic angiomyolipoma. The patient was treated with a partial nephrectomy. Three years later, she developed rapidly enlarging liver nodules. A fine-needle aspiration of the liver confirmed the presence of pleomorphic epithelioid cells morphologically and immunohistochemically identical to those comprising the primary renal tumor. After two cycles of treatment with doxorubicin, there was a 50% reduction in the size of the tumors with marked improvement in performance status. We believe this case confirms the existence of a malignant epithelioid angiomyolipoma. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cibas, ES (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 26 TC 92 Z9 109 U1 0 U2 2 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 JAN PY 2001 VL 25 IS 1 BP 121 EP 126 DI 10.1097/00000478-200101000-00014 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 384GH UT WOS:000165934100014 PM 11145246 ER PT J AU Pawlik, TM Souba, WW Bode, BP AF Pawlik, TM Souba, WW Bode, BP TI Asparagine uptake in rat hepatocytes: Resolution of a paradox and insights into substrate-dependent transporter regulation SO AMINO ACIDS LA English DT Article DE amino acids; transport; asparagine; glutamine; hepatocytes; cell volume; phosphatidylinositol 3-kinase ID AMINO-ACID-TRANSPORT; HEPATIC GLUTAMINE TRANSPORT; PRIMARY CULTURED-HEPATOCYTES; ORNITHINE DECARBOXYLASE; CELL-VOLUME; SYSTEM-N; NITROGEN-METABOLISM; LIVER; INDUCTION; STIMULATION AB Extracellular asparagine has previously been shown to markedly stimulate both ornithine decarboxylase and System N-mediated glutamine transport activities in hepatocytes by a transport-dependent mechanism. However, as a weak substrate of its inferred transporter System N, the specific route of asparagine uptake has remained enigmatic. In this study, asparagine transport was studied in detail and shown to be Na+-dependent, Li+-tolerant, stereospecific, and inhibited profoundly by glutamine and histidine. Coupled with competitive inhibition by glutamine (K-i = 2.63 +/- 1.11 mM), the data indicated that asparagine was indeed slowly transported by System N in rat hepatocytes, albeit at rates an order of magnitude less than for glutamine. The differential substrate transport velocities were shown to be attributable to a low transporter asparagine affinity (K-m = 9.3 - 17.5 mM) compared to glutamine (K-m similar to 1mM). Consistent with its slow uptake, asparagine accumulated to a fivefold lesser degree than glutamine after 60 mins, yet stimulated System N activity to the same extent as glutamine. The transaminase inhibitor aminooxyacetate and starvation of the donor animal each enhanced asparagine uptake twofold and augmented subsequent transporter activation. Conversely, asparagine-dependent System N stimulation was abrogated by hyperosmotic media and blunted 30%-40% by phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002. Collectively, the data suggest that System N-mediated asparagine uptake serves an autostimulatory role, mediated by cellular swelling and in part by a PI3K-dependent signal transduction pathway. C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Surg Oncol Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bode, BP (reprint author), St Louis Univ, Dept Biol, 3507 Laclede Ave, St Louis, MO 63103 USA. EM bodebp@slu.edu FU NIGMS NIH HHS [5P50 GM21700-23] NR 41 TC 5 Z9 7 U1 1 U2 1 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0939-4451 EI 1438-2199 J9 AMINO ACIDS JI Amino Acids PY 2001 VL 20 IS 4 BP 335 EP 352 DI 10.1007/s007260170031 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442ZK UT WOS:000169314700001 PM 11452978 ER PT J AU Denman, WT Kaplan, RF Goudsouzian, NG Uejima, T Barcelona, SL Cote, CJ Ginsberg, B Hannallah, RS AF Denman, WT Kaplan, RF Goudsouzian, NG Uejima, T Barcelona, SL Cote, CJ Ginsberg, B Hannallah, RS TI Intramuscular rapacuronium in infants and children - A comparative multicenter study to confirm the efficacy and safety of the age-related tracheal intubating doses of intramuscular rapacuronium (ORG 9487) in two groups of pediatric subjects SO ANESTHESIOLOGY LA English DT Article ID NEUROMUSCULAR BLOCKADE; ADDUCTOR POLLICIS; SUCCINYLCHOLINE; ANESTHESIA; ROCURONIUM; SEVOFLURANE; HALOTHANE; INDUCTION; ORG-9487; MUSCLES AB Background: This multicenter, assessor, blinded, randomized study was conducted to confirm and extend a pilot study in which intramuscular rapacuronium was given to infants and children to confirm efficacy and to evaluate tracheal intubating conditions. Methods: Ninety-six pediatric patients were studied in two groups: infants aged 1 to 12 months (n = 46) and children aged 1 to 3 yr (n = 50). Infants received 2.8 mg/kg and children 4.8 mg/kg of intramuscular rapacuronium during 1 minimum alveolar concentration halothane anesthesia. These two groups were studied in three subgroups, depending on the time (1.5, 3, or 4 min) at which tracheal intubation was attempted after the administration of intramuscular rapacuronium into the deltoid muscle. Neuromuscular data collected included onset time, duration of action, and recovery data during train-of-four stimulation at 0.1 Hz. Data were analyzed by the Cochran-Mantel-Haenszel procedure. Results: The tracheal intubating conditions were deemed acceptable in 17, 36, and 64% of infants and 20, 47, and 71% of children at 1.5, 3, or 4 min, respectively. The mean values for % of control twitch height (T1) 2 min after rapacuronium in both groups were similar. The mean (SD) time required to achieve more than or equal to 95% twitch depression in infants was 6.0 (3.7) versus 5.5 (3.8) min in children. Conclusions: Only 27% of patients achieved clinically acceptable tracheal intubating conditions at 1.5 or 3 min after administration of 2.8 mg/kg and 4.8 mg/kg rapacuronium during 1 minimum alveolar concentration halothane anesthesia. Tracheal intubation conditions at 4 min were acceptable in 69% of subjects. The duration of action of 4.8 mg/kg of rapacuronium in children was longer than 2.8 mg/kg of rapacuronium in infants. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Childrens Natl Med Ctr, Dept Anesthesiol, Washington, DC 20010 USA. Childrens Mem Hosp, Dept Anesthesiol, Chicago, IL 60614 USA. Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA. Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA. RP Denman, WT (reprint author), New England Med Ctr, Dept Anesthesia, 750 Washington St,Box 298, Boston, MA 02111 USA. NR 19 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2001 VL 94 IS 1 BP 3 EP 7 DI 10.1097/00000542-200101000-00006 PG 5 WC Anesthesiology SC Anesthesiology GA 389WU UT WOS:000166262300002 PM 11135715 ER PT J AU Freeman, VL Liao, YL Durazo-Arvizu, R Cooper, RS AF Freeman, VL Liao, YL Durazo-Arvizu, R Cooper, RS TI Height and risk of fatal prostate cancer: Findings from the National Health Interview Survey (1986 to 1994) SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE height; prostatic neoplasms; mortality ID GROWTH-FACTOR-I; INTRAEPITHELIAL NEOPLASIA; ENERGY-INTAKE; DEATH INDEX; TESTOSTERONE; INDUCTION; STATURE; WEIGHT; SWEDEN AB PURPOSE: Height is determined by genetic and nutritional factors mediated through the endocrine system early in life and, thus, may be related to subsequent risk of fatal prostate cancer. This hypothesis was examined in a large representative U.S. national sample. METHODS: Data from the National Health Interview Survey (NHIS) were analyzed to determine whether height was prospectively related to the risk of fatal prostate cancer in 110,042 men age greater than or equal to 50 years old interviewed between 1986 and 1994. Height was self-reported and vital status and causes of death ascertained using the National Death Index. Endpoints were deaths that listed prostate cancer as the underlying cause and deaths with any mention of prostate cancer. Relative risks (RR) and their 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for age, race, weight, and education. RESULTS: Six hundred and thirty-three deaths listing of prostate cancer as the underlying cause and 910 deaths with any mention of prostate cancer were identified. Height was associated neither with risk of death with prostate cancer Listed as the underlying cause nor with risk of death with any mention of prostate cancer (multivariate p for trend = 0.1318 and 0.0698, respectively). Risks were marginally greater among the tallest men compared to the shortest (less than or equal to 171.4 vs, greater than or equal to 182.9 cm), but not significantly (RR = 1.21, 95% CI = 0.92 to 1.51, and RR = 1.24, 95% CI = 0.98 to 1.58 for 'underlying cause' and 'any mention', respectively). CONCLUSIONS: Height alone was not related to risk of fatal prostate cancer in this population. (C) 2000 Elsevier Science Inc. All rights reserved. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, Res Serv 151, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. RP Freeman, VL (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, Res Serv 151, Hines, IL 60141 USA. FU PHS HHS [CCU512480] NR 44 TC 8 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2001 VL 11 IS 1 BP 22 EP 27 DI 10.1016/S1047-2797(00)00172-1 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 386QU UT WOS:000166073700004 PM 11164116 ER PT J AU Gomez-Tortosa, E MacDonald, ME Friend, JC Taylor, SAM Weiler, LJ Cupples, LA Srinidhi, J Gusella, JF Bird, ED Vonsattel, JP Myers, RH AF Gomez-Tortosa, E MacDonald, ME Friend, JC Taylor, SAM Weiler, LJ Cupples, LA Srinidhi, J Gusella, JF Bird, ED Vonsattel, JP Myers, RH TI Quantitative neuropathological changes in presymptomatic Huntington's disease SO ANNALS OF NEUROLOGY LA English DT Article ID INTRANUCLEAR INCLUSIONS; TRINUCLEOTIDE REPEAT; RAT-BRAIN; NEURONS; NUCLEAR; INSTABILITY; PROTEIN; LECTIN; DEATH; CELLS AB Morphometric studies of the tail of the caudate nucleus, the site where the pathology is first seen, were performed on 16 brain specimens collected from individuals at risk for inheriting Huntington's disease (HD), Medical records and information obtained from immediate family members indicated that all had died without symptoms of HD. Six individuals had 37 or more CAG repeats and were designated HD gene carriers, whereas 10 were determined to be non-carriers. Cell counts of the tail of the caudate nucleus revealed an increased density of oligodendrocytes among the presymptomatic HD gene carriers (mean cells/field: carriers = 40.0, noncarrier = 21.3; age, sex, repeated measure adjusted F[126] 11.7, p = 0.0008). No statistically significant differences were found between HD carriers and noncarriers in the density of neurons (carriers = 16.9, noncarriers = 15.5), astrocytes (carriers = 27.8, noncarriers = 21.3) or microglial cells (carriers = 7.9, noncarriers = 5.6). Ubiquitin immunostaining performed in 3 gene carriers revealed intranuclear inclusions in all 3 cases, including 1, with 37 repeats, who died 3 decades before the expected age for onset of the clinical syndrome. Normal densities of other cell types and careful macroscopic examination suggest that the increase in oligodendroglial density is not a consequence of atrophy and may instead reflect a developmental effect of the HD gene. C1 McLean Hosp, Mailman Res Ctr, Belmont, MA 02178 USA. Kingston Gen Hosp, Kingston, ON K7L 2V7, Canada. Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Myers, RH (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St, Boston, MA 02118 USA. EM rmyers@bu.edu NR 25 TC 51 Z9 51 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2001 VL 49 IS 1 BP 29 EP 34 DI 10.1002/1531-8249(200101)49:1<29::AID-ANA7>3.0.CO;2-B PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 402CG UT WOS:000166968000005 ER PT J AU Bertram, L Guenette, S Jones, J Keeney, D Mullin, K Crystal, A Basu, S Yhu, S Deng, A Rebeck, GW Hyman, BT Go, R McInnis, M Blacker, D Tanzi, R AF Bertram, L Guenette, S Jones, J Keeney, D Mullin, K Crystal, A Basu, S Yhu, S Deng, A Rebeck, GW Hyman, BT Go, R McInnis, M Blacker, D Tanzi, R TI No evidence for genetic association or linkage of the cathepsin D (CTSD) exon 2 polymorphism and Alzheimer disease SO ANNALS OF NEUROLOGY LA English DT Article ID SIB TRANSMISSION/DISEQUILIBRIUM TEST; SIBSHIP TEST; ONSET; AGE AB Two recent case-control studies have suggested a strong association of a missense polymorphism in exon 2 of the cathepsin D gene (CTSD) and Alzheimer disease (AD). However, these findings were not confirmed in another independent study. We analyzed this polymorphism in two large and independent AD study populations and did not detect an association between CTSD and AD. The first sample was family-based and included 436 subjects from 134 sibships discordant for AD that were analyzed using the sibship disequilibrium test (SDT, p 0.68) and the sib transmission/disequilibrium test (Sib-TDT, p = 0.81). The second sample of 200 AD cases and 182 cognitively normal controls also failed to show significant differences in the allele or genotype distribution in cases versus controls (X-2, p = 0.91 and p = 0.88, respectively). In addition, two-point linkage analyses in an enlarged family sample (n = 670) did not show evidence for linkage of the chromosomal region around CTSD. Thus, our analyses on more than 800 subjects suggest that if an association between the CTSD exon 2 polymorphism and AD exists, it is likely to be smaller than previously reported. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Johns Hopkins Univ, Inst Med, Dept Psychiat, Baltimore, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tanzi, R (reprint author), Massachusetts Gen Hosp E, Genet & Aging Unit, 149 13th St, Charlestown, MA 02129 USA. RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 16 TC 28 Z9 29 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2001 VL 49 IS 1 BP 114 EP 116 DI 10.1002/1531-8249(200101)49:1<114::AID-ANA18>3.0.CO;2-M PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 402CG UT WOS:000166968000016 PM 11198280 ER PT J AU Shinomori, Y Spack, DS Jones, DD Kimura, RS AF Shinomori, Y Spack, DS Jones, DD Kimura, RS TI Volumetric and dimensional analysis of the guinea pig inner ear SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE guinea pig; inner ear; volume ID ENDOLYMPHATIC HYDROPS; MEMBRANE AB The objective of this study was to provide accurate volumetric data on the fluid spaces and soft tissue in the guinea pig inner ear by measuring all histologic serial sections by means of Metamorph Imaging Software at 400x to 1,000x magnification. The total endolymph volume of the inner ear was 4.691 mm(3), of which 1.50l mm(3) was in the cochlea, 3.090 mm(3) in the vestibular labyrinth, and 0.100 mm(3) in the endolymphatic duct and sac. The total perilymph volume was 15.938 mm(3), of which 8.867 mm(3) was in the cochlea and 7.071 mm(3) in the vestibular labyrinth. The volume of the organ of Corti per millimeter length increased toward the apex, but the volumes of the stria vascularis, spiral ligament, and spiral limbus decreased. The volume of the macula utriculi was larger than that of the macula sacculi. The measurement of the luminal surface area of the stria vascularis was 3.944 mm(2), and that of the vestibular dark cells was 5.772 mm(2). C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Kimura, RS (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC00073] NR 18 TC 48 Z9 49 U1 0 U2 3 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 JAN PY 2001 VL 110 IS 1 BP 91 EP 98 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 394RM UT WOS:000166537100017 PM 11201817 ER PT J AU Zegzula, HD Lee, WPA AF Zegzula, HD Lee, WPA TI Infusion port dislodgment of bilateral breast tissue expanders after MRI SO ANNALS OF PLASTIC SURGERY LA English DT Article ID BIOMEDICAL IMPLANTS; RECONSTRUCTION; FIELD AB Tissue expanders are placed routinely for breast reconstruction, and magnetic resonance imaging (MRI) is a common diagnostic procedure. Many studies have reported on the safety of MRI in patients with nonferromagnetic implants; however, many tissue expanders contain ferromagnetic components. The authors present a case of bilateral tissue expander infusion port dislodgment after MRI. A 56-year-old woman underwent bilateral mastectomy and immediate reconstruction with McGhan BIOSPAN tissue expanders. These implants contain integral nonferromagnetic infusion ports, as well as small, powerful Magna-Site magnets. Several weeks postoperatively the patient underwent MRI of her spine, which was ordered by her primary physician for back pain. Subsequently, the infusion ports could not be located with the finder magnet. A chest radiograph was obtained, which demonstrated bilateral dislodgment of the infusion ports. Surgical removal and replacement of the tissue expanders were required. Safety considerations of MRI have been discussed extensively in the literature, and data on MRI with various implanted devices have been obtained. The potential risks of performing MRI on patients with metallic implants include conduction of electrical currents, heating of the implant, misinterpretation resulting from artifact, and the possibility of movement or dislodgment of the implant. The small magnet integral to many tissue expanders may be overlooked by patients and physicians during pre-MRI screening. All patients undergoing tissue expansion with implants that contain integral ports should be thoroughly warned about the potential hazards of MRI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. RP Lee, WPA (reprint author), Wang Ambulatory Care Ctr, Suite 453,15 Parkman St, Boston, MA 02114 USA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD JAN PY 2001 VL 46 IS 1 BP 46 EP 48 DI 10.1097/00000637-200101000-00009 PG 3 WC Surgery SC Surgery GA 391PR UT WOS:000166364800009 PM 11192033 ER PT J AU Hettiaratchy, S Moloney, D Clarke, J AF Hettiaratchy, S Moloney, D Clarke, J TI Patients with acute skin loss: are they best managed on a burns unit? SO ANNALS OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND LA English DT Article DE acute skin loss; management; burn unit ID TOXIC EPIDERMAL NECROLYSIS; SURGICAL-MANAGEMENT AB Patients who are critically ill and have large areas of skin loss or breakdown present a difficult management problem. They require the combination of intensive therapy facilities to support failing organs and specialized skin care, sometimes including extensive debridement and reconstruction. The expertise required for both aspects of treatment are found uniquely on a burns unit. We present five patients with large areas of cutaneous loss or damage secondary to a variety of non-burn aetiologies who were managed on a burns unit. We suggest that a burns unit may be the most appropriate place for such patients to be treated during both the acute phase of their illness and the later stages of surgical reconstruction and physical rehabilitation. C1 Chelsea & Westminster Hosp, Burn Unit, London, England. RP Hettiaratchy, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WACC-453, Boston, MA 02114 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU ROYAL COLL SURGEONS ENGLAND PI LONDON PA 35-43 LINCOLN'S INN FIELDS, LONDON WC2A 3PN, ENGLAND SN 0035-8843 J9 ANN ROY COLL SURG JI Ann. R. Coll. Surg. Engl. PD JAN PY 2001 VL 83 IS 1 BP 26 EP 29 PG 4 WC Surgery SC Surgery GA 396QA UT WOS:000166647000007 PM 11212445 ER PT J AU Mercola, M Levin, M AF Mercola, M Levin, M TI Left-right asymmetry determination in vertebrates SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY LA English DT Review DE laterality; TGF beta; Nodal; Shh; cilia; gap junctions; mice; chick; Xenopus ID LEFT-RIGHT AXIS; GAP JUNCTIONAL COMMUNICATION; LEFT-RIGHT SPECIFICATION; NODAL-RELATED SIGNALS; EARLY XENOPUS EMBRYO; SITUS-INVERSUS; CHICK-EMBRYO; INSERTIONAL MUTATION; MESODERM INDUCTION; PRIMITIVE STREAK AB A distinctive and essential feature of the vertebrate body is a pronounced left-right asymmetry of internal organs and the central nervous system. Remarkably, the direction of left-right asymmetry is consistent among all normal individuals in a species and, for many organs, is also conserved across species, despite the normal health of individuals with mirror-image anatomy. The mechanisms that determine stereotypic left-right asymmetry have fascinated biologists for over a century. Only recently, however, has our understanding of the left-right patterning been pushed forward by links to specific genes and proteins. Here we examine the molecular biology of the three principal steps in left-right determination: breaking bilateral symmetry, propagation and reinforcement of pattern, and the translation of pattern into asymmetric organ morphogenesis. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Forsyth Inst, Boston, MA 02115 USA. RP Mercola, M (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL59502, HL63271] NR 147 TC 113 Z9 115 U1 0 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 2001 VL 17 BP 779 EP 805 DI 10.1146/annurev.cellbio.17.1.779 PG 31 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 497HF UT WOS:000172448800023 PM 11687504 ER PT J AU Finch, CE Ruvkun, G AF Finch, CE Ruvkun, G TI The genetics of aging SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS LA English DT Review DE longevity; metabolism; phylogeny; polymorphism; senescence ID TRANSCRIPTION FACTOR FKHR; PROTEIN-KINASE-B; EXTENDED LIFE-SPAN; NEMATODE CAENORHABDITIS-ELEGANS; CU/ZN SUPEROXIDE-DISMUTASE; DAUER LARVA DEVELOPMENT; PANCREATIC BETA-CELLS; AGE-1 PI3 KINASE; C-ELEGANS; OXIDATIVE STRESS AB The genetic analysis of life span has only begun in mammals, invertebrates, such as Caenorhabditis elegans and Drosophila, and yeast. Even at this primitive stage of the genetic analysis of aging, the physiological observations that rate of metabolism is intimately tied to life span is supported. In many examples from mice to worms to flies to yeast, genetic variants that affect life span also modify metabolism. Insulin signaling regulates life span coordinately with reproduction, metabolism, and free radical protective gene regulation in C. elegans. This may be related to the findings that caloric restriction also regulates mammalian aging, perhaps via the modulation of insulin-like signaling pathways. The nervous system has been implicated as a key tissue where insulin-like signaling and free radical protective pathways regulate life span in C. elegans and Drosophila. Genes that determine the life span could act in neuroendocrine cells in diverse animals. The involvement of insulin-like hormones suggests that the plasticity in life spans evident in animal phylogeny may be due to variation in the timing of release of hormones that control vitality and mortality as well as variation in the response to those hormones. Pedigree analysis of human aging may reveal variations in the orthologs of the insulin pathway genes and coupled pathways that regulate invertebrate aging. Thus, genetic approaches may identify a set of circuits that was established in ancestral metazoans to regulate their longevity. C1 Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Finch, CE (reprint author), Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. NR 130 TC 219 Z9 259 U1 2 U2 20 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2001 VL 2 BP 435 EP 462 DI 10.1146/annurev.genom.2.1.435 PG 30 WC Genetics & Heredity SC Genetics & Heredity GA 476AQ UT WOS:000171204200018 PM 11701657 ER PT J AU Arnaout, MA AF Arnaout, MA TI Molecular genetics and pathogenesis of autosomal dominant polycystic kidney disease SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE polycystic kidneys; polycystins; vascular aneurysms; adherens junctions; cell polarity ID KIDNEY-DISEASE-2 PKD2 GENE; BLOOD-PRESSURE CONTROL; LEFT-VENTRICULAR MASS; RENAL CYST FORMATION; INTRACRANIAL ANEURYSMS; EPITHELIAL-CELLS; FLUID SECRETION; TRANSGENIC MICE; POLYCYSTIC-KIDNEY-DISEASE-1 PKD1; CARDIOVASCULAR-ABNORMALITIES AB Autosomal dominant polycystic kidney disease (ADPKD) is a common and systemic disease characterized by formation of focal cysts. Of the three potential causes of cysts, downstream obstruction, compositional changes in extracellular matrix, and proliferation of partially dedifferentiated cells, evidence strongly supports the latter as the primary abnormality. In the vast majority of cases, the disease is caused by mutations in PKD1 or PKD2, and appears to be recessive at the cellular level. Somatic second hits in the normal allele of cells containing the germ line mutation initiate or accelerate formation of cysts. The intrinsically high frequency of somatic second hits in epithelia appears to be sufficient to explain the frequent occurrence of somatic second hits in the disease-causing genes. PKD1 and PKD2 encode a putative adhesive/ion channel regulatory protein and an ion channel, respectively. The two proteins interact directly in vitro. Their cellular and subcellular localization suggest that they may also function independently in a common signaling pathway that may involve the membrane skeleton and that links cell-cell acid cell-matrix adhesion to the development of cell polarity. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [P01 DK 54711] NR 225 TC 73 Z9 73 U1 0 U2 2 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2001 VL 52 BP 93 EP 123 DI 10.1146/annurev.med.52.1.93 PG 31 WC Medicine, General & Internal SC General & Internal Medicine GA 407ZW UT WOS:000167302900007 PM 11160770 ER PT J AU DeMeo, DL Ginns, LC AF DeMeo, DL Ginns, LC TI Lung transplantation at the turn of the century SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE allograft; rejection; immunosuppression; infection; survival ID BRONCHIOLITIS OBLITERANS SYNDROME; QUALITY-OF-LIFE; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; EXTRACORPOREAL MEMBRANE-OXYGENATION; PRIMARY PULMONARY-HYPERTENSION; PRIMARY GRAFT FAILURE; HEART-LUNG; ACUTE REJECTION; RISK-FACTORS; CYTOMEGALOVIRUS-INFECTION AB Lung transplantation has become a viable treatment option for patients with end-stage lung disease. Donor selection and organ allocation must follow specific guidelines. Single, bilateral, and living-donor lobar transplantation have all been performed successfully for a variety of diseases. Complications include reimplantation response and airway complications. Rejection may occur in the hyperacute, acute, or chronic settings and requires judicious management with immunosuppression. Infection and malignancy remain potential complications of the commitment to lifelong systemic immunosuppression. Survival statistics have remained encouraging and continue to improve with experience. Improved exercise tolerance and quality of life have been demonstrated in the years following transplantation. Remaining obstacles include limited donor organ availability, long-term graft function, and patient survival. However, ongoing advances in immune tolerance and standardized training of physicians in the care of transplant patients should carry lung transplant forward in the twenty-first century. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lung Transplant Program, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP DeMeo, DL (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. NR 118 TC 32 Z9 32 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2001 VL 52 BP 185 EP 201 DI 10.1146/annurev.med.52.1.185 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 407ZW UT WOS:000167302900011 PM 11160774 ER PT J AU Daley, J Henderson, WG Khuri, SF AF Daley, J Henderson, WG Khuri, SF TI Risk-adjusted surgical outcomes SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE morbidity; mortality; risk adjustment; quality of care; logistic regression ID POSTOPERATIVE MORBIDITY; PROGNOSTIC PREDICTION; BYPASS-SURGERY; REPORT CARDS; HEALTH-CARE; QUALITY; MORTALITY AB Measures of risk-adjusted outcome are particularly suited for the assessment of the quality of surgical care. The reliability of measures of quality that use surgical outcomes is enhanced by prospective data acquisition and should be adjusted for the preoperative severity of illness. Such measures should be based only on reliable and validated data, and they should apply state-of-the-art analytical methods. The risk-adjusted postoperative mortality rate is useful as a quality measure only in specialties and operations expected to have a high rate of postoperative deaths. Risk-adjusted complications are more common but are limited as a comparative measure of quality by a lack of uniform definitions and data collection mechanisms. In specialties in which the expected postoperative mortality is low, risk-adjusted functional outcomes are promising measures for the assessment of the quality of surgical care. Measures of cost and patient satisfaction should also be incorporated in systems designed to measure the quality and cost-effectiveness of surgical care. C1 Harvard Univ, Sch Med, Boston Vet Adm Healthcare Syst, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Partners Healthcare Syst, Boston, MA 02114 USA. Vet Adm Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. Harvard Univ, Brigham & Womens Hosp, Dept Surg, Boston, MA 02132 USA. Boston Vet Adm Healthcare Syst, Boston, MA 02132 USA. RP Daley, J (reprint author), Harvard Univ, Sch Med, Boston Vet Adm Healthcare Syst, Dept Med, 50 Staniford St, Boston, MA 02114 USA. NR 44 TC 75 Z9 77 U1 0 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2001 VL 52 BP 275 EP 287 DI 10.1146/annurev.med.52.1.275 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 407ZW UT WOS:000167302900016 PM 11160779 ER PT J AU Wekerle, T Sykes, M AF Wekerle, T Sykes, M TI Mixed chimerism and transplantation tolerance SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE macrochimerism; organ transplantation; bone marrow transplantation; costimulatory blockade; xenotransplantation ID BONE-MARROW TRANSPLANTATION; SKIN ALLOGRAFT TOLERANCE; DONOR-SPECIFIC TOLERANCE; NONLETHAL PREPARATIVE REGIMEN; INTRATHYMIC CLONAL DELETION; WHOLE-BODY IRRADIATION; VERSUS-HOST DISEASE; LARGE-ANIMAL-MODEL; T-CELL DEPLETION; HEMATOPOIETIC CHIMERISM AB Achieving transplanatation tolerance is an important goal in the effort to reduce long-term morbidity and mortality in organ transplant recipients. Robust, lifelong, donor-specific tolerance can be reliably achieved by induction of mixed chimerism in various animal models. To date. the clinical application of these protocols has been impeded partly by the potential toxicity of the required host conditioning regimens and the lack of successful studies in large animals. This article reviews the progress achieved in recent years in developing considerably milder conditioning protocols in rodents, and in extending some of these models to achieve permanent mixed chimerism and tolerance in large animals. Advances in the induction of xenogeneic tolerance through mixed chimerism are also discussed. C1 Univ Vienna, Vienna Gen Hosp, Dept Surg, A-1090 Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, BMT Sect,Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Wekerle, T (reprint author), Univ Vienna, Vienna Gen Hosp, Dept Surg, Waehringer Guertel 18, A-1090 Vienna, Austria. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01 HL49915-04, P01 HL18646, R01 HL54038] NR 106 TC 120 Z9 137 U1 0 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2001 VL 52 BP 353 EP + DI 10.1146/annurev.med.52.1.353 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 407ZW UT WOS:000167302900021 PM 11160784 ER PT J AU Stock, UA Vacanti, JP AF Stock, UA Vacanti, JP TI Tissue engineering: Current state and prospects SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE autologous cells; biodegradable scaffolds; organs grown in vitro ID SMALL-INTESTINAL SUBMUCOSA; BIODEGRADABLE POLYMER SCAFFOLDS; IN-VIVO; HEPATOCYTE TRANSPLANTATION; ENDOTHELIAL-CELLS; GRAFT; MODEL; REGENERATION; RECONSTITUTION; CHONDROCYTES AB Organ shortage and suboptimal prosthetic or biological materials for repair or replacement of diseased or destroyed human organs and tissues are the main motivation for increasing research in the emerging field of tissue engineering. No organ or tissue is excluded from this multidisciplinary research field, which aims to provide vital tissues with the abilities to function, grow, repair, and remodel. There are several approaches to tissue engineering, including the use of cells, scaffolds, and the combination of the two. The most common approach is biodegradable or resorbable scaffolds configured to the shape of the new tissue (e.g. a heart valve). This scaffold is seeded with cells, potentially derived from either biopsies or stem cells. The seeded cells proliferate, organize, and produce cellular and extracellular matrix. During this matrix formation, the starter matrix is degraded. resorbed, or metabolized. First clinical trials using skin or cartilage substitutes are currently under way. Both the current state of the field and future prospects are discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Innovat Minimally Invas Therapy, Boston, MA 02114 USA. RP Stock, UA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Innovat Minimally Invas Therapy, 55 Fruit St, Boston, MA 02114 USA. NR 61 TC 264 Z9 289 U1 6 U2 68 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2001 VL 52 BP 443 EP 451 DI 10.1146/annurev.med.52.1.443 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 407ZW UT WOS:000167302900025 PM 11160788 ER PT J AU Sheng, M Sala, C AF Sheng, M Sala, C TI PDZ domains and the organization of supramolecular complexes SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE protein targeting; scaffold protein; postsynaptic density; INAD; PSD-95 ID NITRIC-OXIDE SYNTHASE; POSTSYNAPTIC DENSITY PROTEIN; EXCHANGER REGULATORY FACTOR; TUMOR-SUPPRESSOR GENE; RECEPTOR-INTERACTING PROTEIN; SYNAPTIC VESICLE EXOCYTOSIS; KINASE-ASSOCIATED PROTEIN; LONG-TERM POTENTIATION; CELL-ADHESION MOLECULE; RECTIFIER K+-CHANNEL AB PDZ domains are modular protein interaction domains that bind in a sequence-specific fashion to short C-terminal peptides or internal peptides that fold in a beta -finger. The diversity of PDZ binding specificities can be explained by variable amino acids lining the peptide-binding groove of the PDZ domain. Abundantly represented in Caenorhabditis elegans, Drosophila melanogaster, and mammalian genomes, PDZ domains are frequently found in multiple copies or are associated with other protein-binding motifs in multidomain scaffold proteins. PDZ-containing proteins are typically involved in the assembly of supramolecular complexes that perform localized signaling functions at particular subcellular locations. Organization around a PDZ-based scaffold allows the stable localization of interacting proteins and enhances the rate and fidelity of signal transduction within the complex. Some PDZ-containing proteins are more dynamically regulated in distribution and may also be involved in the trafficking of interacting proteins within the cell. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RI Sala, Carlo/A-2493-2009 OI Sala, Carlo/0000-0003-0662-9523 FU NINDS NIH HHS [NS35050] NR 143 TC 856 Z9 877 U1 6 U2 50 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2001 VL 24 BP 1 EP 29 DI 10.1146/annurev.neuro.24.1.1 PG 33 WC Neurosciences SC Neurosciences & Neurology GA 456XY UT WOS:000170109100001 PM 11283303 ER PT J AU Leaf, A AF Leaf, A TI Medicine or physiology: My personal mix SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE autobiography; polyunsaturated fatty acids; cell volume regulation; sodium transport; preventive medicine ID POLYUNSATURATED FATTY-ACIDS; RAT CARDIAC MYOCYTES; NA+ CHANNELS; LONG-CHAIN; PREVENTION; ARRHYTHMIAS; DEATH; DOGS C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. RP Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. EM aleaf@partners.org NR 27 TC 1 Z9 1 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 EI 1545-1585 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2001 VL 63 BP 1 EP 14 PG 14 WC Physiology SC Physiology GA 421PC UT WOS:000168071900002 PM 11181946 ER PT J AU Dockray, GJ Varro, A Dimaline, R Wang, T AF Dockray, GJ Varro, A Dimaline, R Wang, T TI The gastrins: Their production and biological activities SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE parietal cell; enterochromaffin-like cell; gastric epithelium; gastric acid ID GLYCINE-EXTENDED GASTRIN; ENTEROCHROMAFFIN-LIKE CELLS; RAT ANTRAL MUCOSA; CANINE-G-CELLS; CHOLECYSTOKININ-B/GASTRIN RECEPTOR; HISTIDINE-DECARBOXYLASE PROMOTER; VESICULAR MONOAMINE TRANSPORTER; PHORBOL 12-MYRISTATE 13-ACETATE; PROGASTRIN-DERIVED PEPTIDES; REGENERATING-GENE PROTEIN AB Gastric epithelial organization and function are controlled and maintained by a variety of endocrine and paracrine mediators. Peptides encoded by the gastrin gene are an important part of this system because targeted deletion of the gene, or of the gastrin-CCKB receptor gene, leads to decreased numbers of parietal cells and decreased gastric acid secretion. Recent studies indicate that the gastrin precursor, preprogastrin, gives rise to a variety of products, each with a distinctive spectrum of biological activity. The conversion of progastrin to smaller peptides is regulated by multiple mechanisms including prohormone phosphorylation and secretory vesicle pH, Progastrin itself stimulates colonic epithelial proliferation; biosynthetic intermediates (Gly-gastrins) stimulate colonic epithelial proliferation and gastric epithelial differentiation; and C-terminally amidated gastrins stimulate colonic proliferation, gastric epithelial proliferation and differentiation, and acid secretion. The effects of progastrin-derived peptides on gastric epithelial function are mediated in part by release of paracrine factors that include histamine, epidermal growth factor (EGF)-receptor ligands, and Reg. The importance of the appropriate regulation of this system is shown by the observation that prolonged moderate hypergastrinemia in transgenic mice leads to remodelling of the gastric epithelium, and in the presence of Helicobacter. to gastric cancer. C1 Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Dockray, GJ (reprint author), Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 131 TC 233 Z9 238 U1 0 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2001 VL 63 BP 119 EP 139 DI 10.1146/annurev.physiol.63.1.119 PG 23 WC Physiology SC Physiology GA 421PC UT WOS:000168071900007 PM 11181951 ER PT J AU Cao, H Baldini, RL Rahme, LG AF Cao, H Baldini, RL Rahme, LG TI Common mechanisms for pathogens of plants and animals SO ANNUAL REVIEW OF PHYTOPATHOLOGY LA English DT Review DE microbial pathogenesis; Pseudomonas aeruginosa; Bulkholderia cepacia; Erwinia spp.; common virulence factors ID AERUGINOSA VIRULENCE FACTORS; RHAMNOLIPID BIOSURFACTANT SYNTHESIS; ENTEROPATHOGENIC ESCHERICHIA-COLI; DISEASE RESISTANCE GENES; LACTONE SIGNAL MOLECULES; SYRINGAE PV. MACULICOLA; HEAT-SHOCK-PROTEIN; LUXR-LUXI FAMILY; NF-KAPPA-B; PSEUDOMONAS-AERUGINOSA AB The vast evolutionary gulf between plants and animals-in terms of structure, composition, and many environmental factors-would seem to preclude the possibility that these organisms could act as receptive hosts to the same microorganism. However, some pathogens are capable of establishing themselves and thriving in members of both the plant and animal kingdoms. The identification of functionally conserved virulence mechanisms required to infect hosts of divergent evolutionary origins demonstrates the remarkable conservation in some of the underlying virulence mechanisms of pathogenesis and is changing researchers' thinking about the evolution of microbial pathogenesis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Shriners Burn Hosp, Boston, MA 02114 USA. RP Rahme, LG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RI Baldini, Regina/C-4035-2012 OI Baldini, Regina/0000-0003-4349-6352 NR 135 TC 90 Z9 94 U1 0 U2 8 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4286 J9 ANNU REV PHYTOPATHOL JI Annu. Rev. Phytopathol. PY 2001 VL 39 BP 259 EP + DI 10.1146/annurev.phyto.39.1.259 PG 27 WC Plant Sciences SC Plant Sciences GA 471JW UT WOS:000170927100011 PM 11701866 ER PT S AU Marasco, WA AF Marasco, WA BE Burton, DR TI Intrabodies as antiviral agents SO ANTIBODIES IN VIRAL INFECTION SE Current Topics in Microbiology and Immunology LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE-CHAIN ANTIBODY; VIRAL LIFE-CYCLE; CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN ANTI-GP120 ANTIBODY; HIV-INFECTED INDIVIDUALS; GRAFT-VERSUS-LEUKEMIA; REPLICATION IN-VITRO; INHIBIT EARLY STAGES C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,Jimmy Fund Bldg,Room 824, Boston, MA 02115 USA. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, AI28785] NR 124 TC 18 Z9 18 U1 3 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-41611-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2001 VL 260 BP 247 EP 270 PG 24 WC Immunology; Microbiology SC Immunology; Microbiology GA BU12M UT WOS:000175080600013 PM 11443877 ER PT S AU Woolf, CJ AF Woolf, CJ BE Woolf, CJ TI Mechanism-based evaluation of neuropathic pain SO ANTIEPILEPTIC DRUGS: MECHANISM, MODALITIES AND CLINICAL BENEFITS SE ROYAL SOCIETY OF MEDICINE INTERNATIONAL CONGRESS AND SYMPOSIUM SERIES LA English DT Proceedings Paper CT Symposium on Antiepileptic Drugs - Mechanisms, Modalities and Clinical Benefits CY JUN 17, 2000 CL DEAD SEA, ISRAEL SP Pfizer Pharmaceut Grp ID INFLAMMATORY PAIN; HYPERSENSITIVITY; PLASTICITY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 3 U2 3 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0142-2367 BN 1-85315-476-8 J9 ROY SOC MED INT CONG PY 2001 VL 248 BP 23 EP 32 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA BS44P UT WOS:000169873800003 ER PT S AU Craig, WA AF Craig, WA BE SoulsbySwaffham, P Wilber, R TI Maximising the efficacy of chemotherapy SO ANTIMICROBIA L RESISTANCE SE ROYAL SOCIETY OF MEDICINE INTERNATIONAL CONGRESS AND SYMPOSIUM SERIES LA English DT Proceedings Paper CT Symposium on Antimicrobial Resistance CY MAY 04-05, 2000 CL WASHINGTON, D.C. SP Royal Soc Med, Royal Soc Med Fdn, Tufs Univ Sch Med ID ILL-PATIENTS; PHARMACODYNAMICS C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI 53706 USA. RP Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI 53706 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0142-2367 BN 1-85315-479-2 J9 ROY SOC MED INT CONG PY 2001 VL 247 BP 159 EP 163 PG 5 WC Medicine, General & Internal; Microbiology; Pharmacology & Pharmacy SC General & Internal Medicine; Microbiology; Pharmacology & Pharmacy GA BR98H UT WOS:000168275800024 ER PT J AU Lau, H Ferlan, JT Brophy, VH Rosowsky, A Sibley, CH AF Lau, H Ferlan, JT Brophy, VH Rosowsky, A Sibley, CH TI Efficacies of lipophilic inhibitors of dihydrofolate reductase against parasitic protozoa SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID THYMIDYLATE SYNTHASE GENE; PLASMODIUM-FALCIPARUM; TOXOPLASMA-GONDII; PNEUMOCYSTIS-CARINII; SACCHAROMYCES-CEREVISIAE; DIHYDROPTEROATE SYNTHETASE; SELECTIVE INHIBITORS; ANTIFOLATE ACTIVITY; SEQUENCE-ANALYSIS; RESISTANCE AB Competitive inhibitors of dihydrofolate reductase (DHFR) are used in chemotherapy or prophylaxis of many microbial pathogens, including the eukaryotic parasites Plasmodium falciparum and Toxoplasma gondii. Unfortunately, point mutations in the DHFR gene can confer resistance to inhibitors specific to these pathogens. We have developed a rapid system for testing inhibitors of DHFRs from a variety of parasites. We replaced the DHFR gene from the budding yeast Saccharomyces cerevisiae with the DHFR-coding region from humans, P. falciparum, T. gondii, Pneumocystis carinii, and bovine or human-derived Cryptosporidium parvum. We studied 84 dicyclic and tricyclic 2,4-diaminopyrimidine derivatives in this heterologous system and identified those most effective against the DHFR enzymes from each of the pathogens. Among these compounds, six tetrahydroquinazolines were effective inhibitors of every strain tested, but they also inhibited the human DHFR and were not selective for the parasites. However, two quinazolines and four tetrahydroquinazolines were both potent and selective inhibitors of the P. falciparum DHFR. These compounds show promise for development as antimalarial drugs. C1 Univ Washington, Dept Genet, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Sibley, CH (reprint author), Univ Washington, Dept Genet, Box 357360, Seattle, WA 98195 USA. FU NIAID NIH HHS [R01 AI029904, AI42321, AI29904] NR 49 TC 24 Z9 24 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 JAN PY 2001 VL 45 IS 1 BP 187 EP 195 DI 10.1128/AAC.45.1.187-195.2001 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 384NV UT WOS:000165952500028 PM 11120964 ER PT J AU Kitchen, PRB Smith, HJ Henderson, MA Goldhirsch, A Castiglione-Gertsch, M Coates, AS Gusterson, B Brown, RW Gelber, RD Collins, JP AF Kitchen, PRB Smith, HJ Henderson, MA Goldhirsch, A Castiglione-Gertsch, M Coates, AS Gusterson, B Brown, RW Gelber, RD Collins, JP TI Tubular carcinoma of the breast: Prognosis and response to adjuvant systemic therapy SO ANZ JOURNAL OF SURGERY LA English DT Article DE adjuvant chemotherapy; breast neoplasms; tubular breast carcinoma ID CANCER AB Background: Tubular carcinoma of the breast is an uncommon and usually small tumour, and is thought to have a favourable prognosis. The present study examined the long-term prognosis of patients with tubular breast carcinoma and the roles of axillary dissection and adjuvant therapy. Methods: Eighty-six tubular cases were identified from a large worldwide database of 9520 breast carcinoma patients entered into randomized adjuvant therapy trials run by the International Breast Cancer Study Group from 1978 to 1999. These patients were followed for a median of 12 years. Results: Forty-two (49%) cases were node-positive, of which 33 (79%) had 1-3 nodes involved. Ten (32%) of the 31 smaller tumours (less than or equal to 1 cm in size) were node-positive. Patients with node-positive tubular carcinoma had a significantly better 10-year relapse-free survival (P = 0.006) and survival (P < 0.0001) compared with non-tubular node-positive cases. Overall survival was similar for node-positive and node-negative tubular carcinoma. Overall, 71 patients (83%) received some form of adjuvant systemic therapy. Of the 86 cases, 43 (50%) received more than one course of chemotherapy. There was an 85% decrease in the risk of death for patients who received more than one course of chemotherapy compared to those who did not (hazard ratio 0.15, 95% confidence interval (CI): 0.03-0.82; P = 0.03). Conclusions: Compared to other histological types of breast cancer, tubular carcinoma has a better long-term prognosis. Adjuvant chemotherapy may further improve prognosis and involvement of axillary nodes may not be an indicator for early death due to breast carcinoma. C1 Univ Melbourne, St Vincents Hosp, Dept Surg, Fitzroy, Vic 3065, Australia. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Int Breast Canc Study Grp, Bern, Switzerland. RP Univ Melbourne, St Vincents Hosp, Dept Surg, 41 Victoria Parade, Fitzroy, Vic 3065, Australia. EM pkitchen@ariel.its.unimelb.edu.au RI gusterson, barry/D-3752-2009 FU NCI NIH HHS [CA-75362] NR 21 TC 21 Z9 22 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1445-1433 EI 1445-2197 J9 ANZ J SURG JI ANZ J. Surg. PD JAN PY 2001 VL 71 IS 1 BP 27 EP 31 DI 10.1046/j.1440-1622.2001.02022.x PG 5 WC Surgery SC Surgery GA 414PB UT WOS:000167674300008 PM 11167594 ER PT S AU Sisterson, JM AF Sisterson, JM BE Duggan, JL Morgan, IL TI Ion beam therapy: overview of the world experience SO APPLICATION OF ACCELERATORS IN RESEARCH AND INDUSTRY SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 16th International Conference on the Application of Accelerators in Research and Industry CY NOV 01-05, 2000 CL UNIV NORTH TEXAS, DENTON, TX SP Natl Sci Fdn, US DOE, Amer Phys Soc, Div Nucl Phys HO UNIV NORTH TEXAS ID PROTON RADIOTHERAPY; CANCER AB In 1946, R. R. Wilson first proposed the use of proton beams in radiation therapy. At 19 centers worldwide, over 26,000 patients have been treated with proton beams; similar to 64% of these patients have been treated since 1990. The good long term follow-up results that are available for selected treatment sites has led to an increased interest in having proton radiation therapy available in a hospital setting. The first such hospital-based facility began operation in 1990, the second in 1998 and several more are under construction. similar to 2500 patients were treated with helium and neon ions at the first heavy ion facility which closed in 1992. similar to 800-patients have been treated at the two currently operating heavy ion facilities built in the 1990s. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Sisterson, JM (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. NR 16 TC 2 Z9 2 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0015-6 J9 AIP CONF PROC PY 2001 VL 576 BP 865 EP 868 PG 4 WC Materials Science, Characterization & Testing; Physics, Atomic, Molecular & Chemical; Physics, Nuclear; Spectroscopy SC Materials Science; Physics; Spectroscopy GA BT20F UT WOS:000172263600206 ER PT J AU Ross, EV Yashar, S Michaud, N Fitzpatrick, R Geronemus, R Tope, WD Anderson, RR AF Ross, EV Yashar, S Michaud, N Fitzpatrick, R Geronemus, R Tope, WD Anderson, RR TI Tattoo darkening and nonresponse after laser treatment - A possible role for titanium dioxide SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SWITCHED RUBY-LASER; MICROSCOPIC ANALYSIS; LIGHT AB Objective: To examine relationships between chemical composition, biopsy findings, and clinical outcome in laser-treated tattoos. Design: Observational nonblinded retrospective study. Settings: University-based dermatology clinic and private practice. Participants: Twenty patients who underwent biopsy of laser-treated tattoos. Main Outcome Measures: Biopsy specimens were analyzed after laser treatment, and the depths of changed particles were recorded. Ultrastructure of the changed particles was examined by electron microscopy. Presence of inorganic chemicals was determined by x-ray diffraction. Correlation between x-ray diffraction, microscopy, and clinical response was attempted. Results: Of the 20 tattoos, 7 lightened, 9 failed to change, and 4 darkened after laser treatment. There was a significant association between presence of titanium dioxide and poor response to laser therapy. Microscopic studies showed variable changes in the ink particles, but there was a trend toward residual deep green pigment in the resistant tattoos. Also, round dark stippling was observed superficially in the darkened specimens. Conclusions: Titanium is overrepresented in tattoos that respond poorly to laser treatment. Further studies are necessary to show whether this metal is the primary cause of this poor response. C1 USN, Med Ctr, Dept Dermatol, San Diego, CA 92134 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Dermatol Associates, Encinitas, CA USA. Laser & Skin Surg Ctr New York, New York, NY USA. RP Ross, EV (reprint author), USN, Med Ctr, Dept Dermatol, 34800 Bob Wilson Dr,Suite 5, San Diego, CA 92134 USA. NR 13 TC 36 Z9 37 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2001 VL 137 IS 1 BP 33 EP 37 PG 5 WC Dermatology SC Dermatology GA 393EZ UT WOS:000166457400005 PM 11176658 ER PT J AU Nghiem, P AF Nghiem, P TI The "drug vs graft-vs-host disease" conundrum gets tougher, but there is an answer - The challenge to dermatologists SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nghiem, P (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Nghiem, Paul/A-9210-2011 OI Nghiem, Paul/0000-0003-2784-963X NR 9 TC 10 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2001 VL 137 IS 1 BP 75 EP 76 PG 2 WC Dermatology SC Dermatology GA 393EZ UT WOS:000166457400011 PM 11176664 ER PT J AU Afshari, NA Mullally, JE Afshari, MA Steinert, RF Adamis, AP Azar, DT Talamo, JH Dohlman, CH Dryja, TP AF Afshari, NA Mullally, JE Afshari, MA Steinert, RF Adamis, AP Azar, DT Talamo, JH Dohlman, CH Dryja, TP TI Survey of patients with granular, lattice, avellino, and Reis-Bucklers corneal dystrophies for mutations in the BIGH3 and gelsolin genes SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID FINNISH HEREDITARY AMYLOIDOSIS; KERATO-EPITHELIN GENE; CHROMOSOME 5Q; BETA-IG-H3; PROTEIN; SUBSTITUTION; FEATURES; FAMILY; FORM; IIIA AB Objectives: To search for novel mutations that cause corneal stromal dystrophies and to confirm or revise the clinical diagnosis of patients with these mutations. Patients: Through review of the records of the Cogan Eye Pathology Laboratory at the Massachusetts Eye and Ear Infirmary, Boston, and of clinical records, we ascertained 14 unrelated patients with the clinical or histopathologic diagnosis of granular (3 cases), Avellino (5 cases), lattice (5 cases), or Reis-Bucklers (1 case) corneal dystrophy. Methods: Clinical records and histopathologic findings of the index patients and their relatives were reviewed. Patients and selected relatives donated a blood sample from which leukocyte DNA was purified and assayed for mutations in the BIGH3 gene and, in 2 patients, the gelsolin gene, using the polymerase chain reaction and direct genomic sequencing. Results: All index patients with the diagnosis of granular dystrophy or Avellino dystrophy had the missense mutation Arg555Trp or Arg124His, respectively, previously reported in the BIGH3 gene. Of the 5 index patients with a prior diagnosis of lattice dystrophy, 2 had the originally reported lattice mutation (Arg124Cys) in the BIGH3 gene, 1 had a more recently reported missense mutation (His626Arg) in the same gene, 1 had the missense mutation Asp187Asn in the gelsolin gene, and 1 had no detected mutation in either gene. Affected members of the family with Reis-Bucklers dystrophy did not carry the previously reported mutations Arg555Gln or Arg124Leu but instead carried a novel missense mutation Gly623Asp in the BIGH3 gene. Conclusions: Molecular genetic analysis can improve the accuracy of diagnosis of patients with corneal dystrophies. Two patients with a prior diagnosis of lattice corneal dystrophy had their diagnosis changed to gelsolin-related amyloidosis (1 case) or secondary, nonhereditary localized amyloidosis (1 case). A novel mutation in the BIGH3 gene that causes Reis-Bucklers dystrophy was uncovered through this analysis, and another recently reported novel mutation was encountered. These findings serve to expand our knowledge of the spectrum of pathogenic mutations in BIGH3. C1 Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Dryja, TP (reprint author), Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY08683] NR 36 TC 70 Z9 79 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2001 VL 119 IS 1 BP 16 EP 22 PG 7 WC Ophthalmology SC Ophthalmology GA 393EX UT WOS:000166457200001 PM 11146721 ER PT J AU La Rosa, FA Gross, RL Orengo-Nania, S AF La Rosa, FA Gross, RL Orengo-Nania, S TI Central corneal thickness of Caucasians and African Americans in glaucomatous and nonglaucomatous populations SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; INTRAOCULAR-PRESSURE; EYE AB Objective: To determine whether there is a difference in central corneal thickness between African American and Caucasian patients. If present, a difference might alter the measurement of intraocular pressure and potentially the assessment and management of glaucoma in these populations. Methods? Central corneal thickness was measured by means of ultrasound pachymetry in African American (n=56) and Caucasian (n=32) patients with suspected or confirmed glaucoma and control populations of African American (n=26) and Caucasian (n=51) subjects in whom there was no evidence of elevated intraocular pressure or glaucomatous optic nerve damage. Measurements of central corneal thickness were then compared between different subpopulations by means and population distribution analysis. Results A statistically significant difference was noted between the mean (+/-SD) central corneal thickness of all African American (including those with and without glaucoma) (right eye, 531.0+/-36.3 mum; left eye, 530.0 +/- 34.6 pm) and all Caucasian (including those with and without glaucoma) (right eye, 558.0 +/- 34.5 mum; left eye, 557.6 +/- 341.5 mum) patients. Similar results were found when subpopulations were tested. Distribution analysis of central corneal thickness measurements noted the largest duster of African American patients around 520 to 540 mum, whereas the largest cluster of Caucasian patients was between 580 and 600 mum. Conclusions: African Americans were found to have thinner central cornea thickness measurements than Caucasians. This finding in African Americans may lead to lower applanation intraocular pressure readings compared with those of Caucasians, potentially resulting in an underestimation of the actual level of intraocular pressure. C1 Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, Houston, TX 77030 USA. Houston Vet Affairs Hosp, Dept Ophthalmol, Houston, TX USA. RP Orengo-Nania, S (reprint author), Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, 6565 Fannin,Mail Stop NC 205, Houston, TX 77030 USA. NR 15 TC 129 Z9 134 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2001 VL 119 IS 1 BP 23 EP 27 PG 5 WC Ophthalmology SC Ophthalmology GA 393EX UT WOS:000166457200002 PM 11146722 ER PT J AU Volpe, NJ Rizzo, JF Lessell, S AF Volpe, NJ Rizzo, JF Lessell, S TI Acute idiopathic blind spot enlargement syndrome - A review of 27 new cases SO ARCHIVES OF OPHTHALMOLOGY LA English DT Review ID EVANESCENT WHITE-DOT; OCCULT OUTER RETINOPATHY; MULTIFOCAL CHOROIDITIS; DISEASE; MEWDS AB Objective: To describe the clinical findings in patients with acute idiopathic blind spot enlargement (AIBSE). Methods? Medical record review of 27 patients with AIBSE (without sufficient optic nerve head swelling to cause blind spot enlargement) seen in 2 academic neuroophthalmology units. Results: All patients were women aged between 19 and 53 years. Twenty-three patients reported positive visual phenomena. Visual acuity was normal in 16 patients. All patients had enlarged blind spots of variable size and density Dyschromatopsia and afferent pupil defects were prevalent. Ophthalmoscopic features included uveitis, mild optic nerve swelling, granularity of macular pigment, subretinal white dots, and peripapillary pigment disturbances. Twelve of the 13 patients who underwent fluorescein angiography had optic disc staining and 5 had retinal pigment epithelial lesions with late staining. Fullfield electroretinogram results were normal in 8 of 9 patients, although focal electroretinogram results were abnormal in 8 of 9 patients. Photopsia always decreased but visual fields did not improve. Six patients experienced recurrence. Conclusions: The clinical features of AIBSE include photopsia, visual field defects, abnormal findings from fundoscopic and fluorescein angiography, and abnormal results of focal electroretinography. The disease affects the peripapillary retina and may cause an afferent pupillary defect. The striking predilection for the peripapillary retina suggests a local etiologic factor and distinguishes AIBSE from the multiple evanescent white dot syndrome. Unlike patients with multiple evanescent white dot syndrome, recovery of visual field did not occur in patients with AIBSE. C1 Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Volpe, NJ (reprint author), Univ Penn, Scheie Eye Inst, 51 N 39th St, Philadelphia, PA 19104 USA. NR 26 TC 26 Z9 26 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2001 VL 119 IS 1 BP 59 EP 63 PG 5 WC Ophthalmology SC Ophthalmology GA 393EX UT WOS:000166457200008 PM 11146727 ER PT J AU Ray, S Topping, T Young, LHY AF Ray, S Topping, T Young, LHY TI Spontaneous peeling of epiretinal membrane associated with Nd : YAG laser injury SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RETINAL INJURY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Young, LHY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2001 VL 119 IS 1 BP 137 EP 139 PG 3 WC Ophthalmology SC Ophthalmology GA 393EX UT WOS:000166457200023 PM 11146742 ER PT J AU Grabowski, EF Reininger, AJ Petteruti, PG Tsukurov, O Orkin, RW AF Grabowski, EF Reininger, AJ Petteruti, PG Tsukurov, O Orkin, RW TI Shear stress decreases endothelial cell tissue factor activity by augmenting secretion of tissue factor pathway inhibitor SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE tissue factor; endothelial cells; shear stress; tissue factor pathway inhibitor ID FACTOR-X; EXPRESSION; COAGULATION; HEMOSTASIS; ACTIVATION; INDUCTION; THROMBIN; CULTURE; BLOOD; FLOW AB Monolayers of human umbilical vein endothelial cells were activated with 50 U/mL interleukin-1 alpha (IL-1 alpha) for 3 hours and simultaneously conditioned with shear stresses of 0, 0,68, or 13.2 dyne/cm(2) in a parallel-plate flow chamber. In the presence of an inflow buffer containing 100 nmol/L factor X and 10 nmol/L factor VII, production of factor Xa, a measure of functional tissue factor (TF), was determined as the product of outflow concentration of factor Xa (chromogenic assay performed under quasi-static flow conditions after the shear period) and flow rate. Similarly, production of TF pathway inhibitor (TFPI) was estimated as the product of antigenic TFPI (by enzyme-linked immunosorbent assay) in the supernatant and flow rate. In parallel experiments, total RNA was isolated for determination of amplification products of TF mRNA by reverse transcription-polymerase chain reaction. We found that sheer stress reduced factor Xa production (mean+/-SE; n=number of experiments) from 13.33+/-1.14 (n=16) fmol/min x cm(2) at 0 shear stress to 5.70+/-2.51 (n=5) and 0.54+/-0.54 (n=4) fmol/min x cm(2) at shear stresses of 0.68 and 13.2 dyne/cm(2), respectively. At the same time, immunogold labeling showed that TF antigen on the endothelial surface increased >5-fold with shear stress, whereas TFPI antigen on the surface increased 2-fold. The secretion of TFPI (appearance of new supernatant TFPI) rose from 7.4+/-2.4 (n=12) x 10(-3) fmol/min x cm(2) at 0 shear stress to 23.7+/-7.3 (n=9) and 50.2+/-14.3 (n=4) x 10(-3) fmol/min x cm(2) at 0.68 and 13.2 dyne/cm(2), respectively. TF mRNA amplification products were not markedly changed by shear stress. We conclude that acute application of shear stress reduces functional, but not antigenic, expression of TF by intact, activated endothelial cell monolayers in a manner associated with shear stress-augmented endothelial cell secretion of TFPI. C1 Massachusetts Gen Hosp, Cardiovasc Thrombosis Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vasc Surg Res Lab, Boston, MA 02114 USA. RP Grabowski, EF (reprint author), Massachusetts Gen Hosp, Cardiovasc Thrombosis Lab, Blake 255,Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL33095] NR 28 TC 37 Z9 45 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2001 VL 21 IS 1 BP 157 EP 162 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 394ML UT WOS:000166527800024 PM 11145948 ER PT J AU Mountz, JD Zhang, HG Wang, Y Xie, JF Liang, X Hsu, HC Curiel, DT AF Mountz, J. D. Zhang, H-G Wang, Y. Xie, J. F. Liang, X. Hsu, H-C Curiel, D. T. TI AKT regulates TNF-alpha-mediated apoptosis of rheumatoid arthritis synovial fibroblasts SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2001 VL 3 SU 1 MA P8 PG 1 WC Rheumatology SC Rheumatology GA V31MO UT WOS:000208887900009 ER PT J AU Dvorznak, MJ Cooper, RA Corfman, TA AF Dvorznak, MJ Cooper, RA Corfman, TA TI Modification of hybrid III test dummy for use in wheelchair studies. SO ASSISTIVE TECHNOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Ctr Excellence Wheelchairs & Related Technol, Human Engn Res Labs, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PY 2001 VL 13 IS 2 BP 139 EP 140 PG 2 WC Rehabilitation SC Rehabilitation GA 628QY UT WOS:000180008900013 ER PT J AU Takei, A Huang, Y Lopes-Virella, MF AF Takei, A Huang, Y Lopes-Virella, MF TI Expression of adhesion molecules by human endothelial cells exposed to oxidized low density lipoprotein - Influences of degree of oxidation and location of oxidized LDL SO ATHEROSCLEROSIS LA English DT Article DE oxidized low-density lipoproteins; intercellular adhesion molecule-1; endothelial cells; atherosclerosis ID MICROVASCULAR DYSFUNCTION; ATHEROSCLEROTIC PLAQUES; P-SELECTIN; DEGRADATION; COLLAGENS; BINDING; LESIONS; GENE AB The main objective of this study was to determine the influence of the degree of low density lipoprotein (LDL) oxidation and the location of oxidized LDL (oxLDL) on expression of adhesion molecules on endothelial cells (EC). OxLDL preparations 1-4 with different degrees of oxidative modification were studied. All preparations of oxLDL, after addition to the medium, stimulated the expression of intercellular adhesion molecule-1 (ICAM-1) by human umbilical vein endothelial cells (HUVEC) as determined by cell-ELISA. Concentration-dependent studies examining ICAM-1 expression by HUVEC showed that the minimal concentration of oxLDL which significantly stimulated ICAM-1 expression was 5 mug/ml, suggesting that the predicted physiological concentration of oxLDL in plasma may be not high enough to elicit a substantial increase of ICAM-1 expression in EC. In contrast, very small amounts (0.15 mug/well) of oxLDL-3 and 4, the more heavily oxidized LDL preparations, stimulated effectively ICAM-1 expression by HUVEC when located below the endothelial cell monolayer by immobilizing to type I collagen. The results suggest that the increased expression of ICAM-1 induced by accumulated oxLDL may be one of the mechanisms by which oxLDL contributes to atherogenesis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29403 USA. Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29403 USA. Kgusha Univ, Dept Med, Fukuoka, Japan. RP Lopes-Virella, MF (reprint author), Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29403 USA. FU NHLBI NIH HHS [HL-55782] NR 29 TC 68 Z9 74 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2001 VL 154 IS 1 BP 79 EP 86 DI 10.1016/S0021-9150(00)00465-2 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 387GZ UT WOS:000166116000009 PM 11137085 ER PT J AU Orban, T Kent, SC Malik, P Milner, JD Schuster, K Jackson, RA Hafler, DA AF Orban, T Kent, SC Malik, P Milner, JD Schuster, K Jackson, RA Hafler, DA TI Heterophile antibodies indicate progression of autoimmunity in human Type 1 diabetes mellitus before clinical onset SO AUTOIMMUNITY LA English DT Article DE Type 1 diabetes; heterophile antibody; human; autoimmunity; disease onset ID ISLET-CELL ANTIBODIES; GLUTAMIC-ACID DECARBOXYLASE; RHEUMATOID FACTORS; INSULIN; IMMUNOGLOBULIN; AUTOANTIBODIES; INTERFERENCE; IMMUNOASSAYS; PREDICTION; SEQUENCES AB We previously reported serum cytokines in a group of long term non-progressors to Type I diabetes; this reactivity detected in ELISA is now identified as heterophile antibody in some sera. Here, we characterize heterophile antibody activity. A 14 kDa-polypeptide from heterophile antibody containing serum bound to an anti-IL-4 column, but IL-4 was not detected by Western blot or by MS/MS sequencing. However, in 2/13 heterophile antibody positive sera, T-cell growth was potentiated and was blocked by an anti-human immunoglobulin. To examine the relationship between low affinity heterophile antibody presence and disease progression, 1100 archived serum samples were analyzed with two pairs of antibodies from 443 diabetes-free first degree relatives of Type 1 diabetes mellitus patients for heterophile antibody; 95 individuals developed diabetes on follow-up. Twenty-two individuals, whose serum was heterophile antibody positive with the second pair of antibodies (but negative with the first pair of antibodies), had a significantly higher incidence of developing diabetes after five years. Thirty-seven individuals with heterophile antibody reactivity with the first pair of antibodies, regardless of reactivity with the second pair of antibodies, had a significantly lower incidence of developing diabetes. While we cannot exclude the presence of genuine cytokine in all sera, these data indicate the presence of distinct groups of heterophile antibodies in patients at high risk to develop diabetes. Thus, anti-Ig heterophilic antibodies with different immunochemical reactivities are linked to the progression of or protection from Type 1 diabetes autoimmunity. C1 Joslin Diabet Ctr, Immunol Sect, Harvard Med Sch, Boston, MA 02215 USA. RP Orban, T (reprint author), Joslin Diabet Ctr, Immunol Sect, Harvard Med Sch, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAID NIH HHS [R01 AI39229-01, R01 AI44447-01, P01 AI39671] NR 37 TC 2 Z9 2 U1 2 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 2001 VL 34 IS 4 BP 247 EP 264 DI 10.3109/08916930109014694 PG 18 WC Immunology SC Immunology GA 524XE UT WOS:000174037500004 PM 11905851 ER PT J AU Pisenti, JM Delany, ME Taylor, RL Abbott, UK Abplanalp, H Arthur, JA Bakst, MR Baxter-Jones, C Bitgood, JJ Bradley, FA Cheng, KM Dietert, RR Dodgson, JB Donoghue, AM Emsley, AB Etches, RJ Frahm, RR Gerrits, RJ Goetinck, PF Grunder, AA Harry, DE Lamont, SJ Martin, GR McGuire, PE Moberg, GP Pierro, LJ Qualset, CO Qureshi, MA Shultz, FT Wilson, BW AF Pisenti, JM Delany, ME Taylor, RL Abbott, UK Abplanalp, H Arthur, JA Bakst, MR Baxter-Jones, C Bitgood, JJ Bradley, FA Cheng, KM Dietert, RR Dodgson, JB Donoghue, AM Emsley, AB Etches, RJ Frahm, RR Gerrits, RJ Goetinck, PF Grunder, AA Harry, DE Lamont, SJ Martin, GR McGuire, PE Moberg, GP Pierro, LJ Qualset, CO Qureshi, MA Shultz, FT Wilson, BW CA Avian Genet Resources Task Force TI Avian genetic resources at risk: An assessment and proposal for conservation of genetic stocks in the USA and Canada SO AVIAN AND POULTRY BIOLOGY REVIEWS LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; PRIMORDIAL GERM-CELLS; EARLY BLASTODERMAL CELLS; ANTERIOR SHANK SKIN; MAREKS-DISEASE; CHICKEN GENOME; CHIMERIC CHICKENS; WHITE LEGHORN; LINKAGE MAP; B-COMPLEX C1 Univ Calif Davis, Genet Resources Conservat Program, Davis, CA 95616 USA. Univ Calif Davis, Dept Anim Sci, Davis, CA USA. USDA ARS, GGPL, BARC E, Beltsville, MD USA. Arbor Acres Inc, Glastonbury, CT USA. Univ Wisconsin, Dept Poultry Sci, Madison, WI USA. Univ British Columbia, Dept Anim Sci, Vancouver, BC, Canada. Cornell Univ, Dept Microbiol Immunol & Parasitol, Ithaca, NY USA. Michigan State Univ, Dept Microbiol, E Lansing, MI USA. USDA, CSREES, Washington, DC USA. Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA USA. CFAR, Ottawa, ON, Canada. Nicholas Turkey Breeding Farms, Sonoma, CA USA. Iowa State Univ, Dept Anim Sci, Ames, IA USA. Univ Calif San Francisco, Dept Anat, Program Dev Biol, San Francisco, CA USA. Univ Connecticut, Storrs Agr Expt Stn, Storrs, CT USA. Univ New Hampshire, Dept Anim & Nutr Sci, Durham, NH USA. Origen Therapeut, S San Francisco, CA USA. RP Pisenti, JM (reprint author), Univ Calif Davis, Genet Resources Conservat Program, Davis, CA 95616 USA. NR 196 TC 24 Z9 25 U1 0 U2 7 PU SCIENCE & TECHNOLOGY LETTERS PI NORTHWOOD PA PO BOX 81,, NORTHWOOD HA6 3DN, MIDDX, ENGLAND SN 1470-2061 J9 AVIAN POULT BIOL REV JI Avian Poult. Biol. Rev. PY 2001 VL 12 IS 1-2 BP 1 EP + PG 97 WC Agriculture, Dairy & Animal Science SC Agriculture GA 424BJ UT WOS:000168212000002 ER PT B AU Young, AB Penney, JB AF Young, AB Penney, JB BE KultasIlinsky, K Ilinsky, IA TI What we know and what we have left to learn SO BASAL GANGLIA AND THALAMUS IN HEALTH AND MOVEMENT DISORDERS LA English DT Proceedings Paper CT International Workshop on Basal Ganglia and Thalamus in Health and Movement Disorders CY MAY 29-31, 2000 CL MOSCOW, RUSSIA SP Eli Lilly, Allergan, Solvay, Medtronic, SmithKline Beecham, Integrated Surg Syst, BrainLab, Radionies, FHC ID STRIATAL PROJECTION NEURONS; BASAL GANGLIA DISORDERS; MEDIUM SPINY NEURONS; SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; FUNCTIONAL-ANATOMY; GLOBUS-PALLIDUS; POSTEROVENTRAL PALLIDOTOMY; MESOPONTINE TEGMENTUM; RECEPTOR ACTIVATION C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Young, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 49 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46543-4 PY 2001 BP 3 EP 10 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA BS24H UT WOS:000169154400001 ER PT J AU Lerner, TJ AF Lerner, TJ TI Positional cloning of the JNCL gene, CLN3 SO BATTEN DISEASE: DIAGNOSIS, TREATMENT, AND RESEARCH SE ADVANCES IN GENETICS INCORPORATING MOLECULAR GENETIC MEDICINE LA English DT Review ID NEURONAL CEROID-LIPOFUSCINOSIS; BATTEN-DISEASE GENE; MITOCHONDRIAL ATP SYNTHASE; DINUCLEOTIDE REPEAT POLYMORPHISM; HUMAN CHROMOSOME-16; LATE-INFANTILE; LOCUS CLN3; LINKAGE DISEQUILIBRIUM; ALLELIC ASSOCIATION; EXON AMPLIFICATION C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Lerner, TJ (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS32099] NR 52 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2660 J9 ADV GENET PY 2001 VL 45 BP 107 EP 121 DI 10.1016/S0065-2660(01)45006-1 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA BX61M UT WOS:000185887400006 PM 11332768 ER PT J AU McNally, RJ Wilhelm, S Buhlmann, U Shin, LM AF McNally, Richard J. Wilhelm, Sabine Buhlmann, Ulrike Shin, Lisa M. TI COGNITIVE INHIBITION IN OBSESSIVE-COMPULSIVE DISORDER: APPLICATION OF A VALENCE-BASED NEGATIVE PRIMING PARADIGM SO BEHAVIOURAL AND COGNITIVE PSYCHOTHERAPY LA English DT Article DE Negative priming; Tipper paradigm; cognitive inhibition; obsessive-compulsive disorder AB We used a negative priming paradigm to test for deficits in cognitive inhibition in patients with obsessive-compulsive disorder (OCD), and to examine whether they exhibit greater inhibitory deficits when lexical targets are threat-related than when they are neutral. The results indicated that OCD patients, relative to healthy control participants, exhibited only marginally significant (p < .10) deficits in negative priming at short (100 ms), but not long (500 ms), stimulus onset asynchronies. There was no evidence that OCD patients exhibited disproportionate difficulty inhibiting negative words, nor was there any evidence that negative priming deficits differed between OCD checkers and OCD noncheckers. C1 [McNally, Richard J.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Buhlmann, Ulrike] Univ Marburg, D-35032 Marburg, Germany. [Shin, Lisa M.] Tufts Univ, Medford, MA 02155 USA. RP McNally, RJ (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM rjm@wjh.harvard.edu NR 4 TC 5 Z9 5 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1352-4658 J9 BEHAV COGN PSYCHOTH JI Behav. Cognit. Psychther. PD JAN PY 2001 VL 29 IS 1 BP 103 EP 106 DI 10.1017/S1352465801001114 PG 4 WC Psychology, Clinical SC Psychology GA V16RV UT WOS:000207887600011 ER PT J AU Lewandrowski, KU Schollmeier, G Ekkemkamp, A Uhthoff, HK Tomford, WW AF Lewandrowski, KU Schollmeier, G Ekkemkamp, A Uhthoff, HK Tomford, WW TI Incorporation of perforated and demineralized cortical bone allografts. Part I: Radiographic and histologic evaluation SO BIO-MEDICAL MATERIALS AND ENGINEERING LA English DT Article ID YAG LASER ABLATION; OSTEOINDUCTION; INDUCTION; IMPLANTS; MATRIX; TISSUE AB Massive cortical bone allografts have been found to incorporate slowly into host bone. They are subject to complications such as nonunion, fatigue fracture and infection. In an attempt to improve osteoinduction in cortical bone allografts, laser perforated and partially demineralized cortical bone allografts were orthotopically transplanted into the sheep tibia. In this model, mid-shaft tibial bone allografts from out-bred sheep donor animals were prepared by partial demineralization and drilling of 0.33-mm diameter holes with a pulsed, 2.94-mum wavelength Erbium:Yttrium-Aluminum-Gar-net laser. Recipient animals of the same out-bred strain were divided into three groups of eight according to the type of cortical allograft used: group 1, fresh-frozen, no treatment; group 2, laser hole grid; and group 3, laser hole grid and partial demineralization. Plain films were taken in two standard views at monthly intervals. Incorporation was evaluated at nine months postoperatively. Longitudinal radiographic data was correlated to a histologic and morphometric evaluation of each bone graft. Computer tomography was used for the latter analysis. Results showed that untreated allografts, although surrounded by a periosteal bone cuff, were poorly incorporated. Partial demineralization lead to excessive resorption of allografts, but little new bone formation. Laser perforation and partial demineralization induced complete incorporation of allografts into the host bone. Based on the results of the radiographic, histologic and morphometric evaluation, the development of laser-perforated and partially demineralized bone allografts was proposed for clinical use. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Marzahn Berufsgenossenschatlicher Unfallklin eV, Krankenhaus Berlin, Unfallkrankenhaus Berlin, Klin Unfall & Wiederherstellungschirurg, Berlin, Germany. Ottawa Gen Hosp, Bone & Joint Res Lab, Ottawa, ON K1H 8L6, Canada. RP Lewandrowski, KU (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs, WACC 508,15 Parkman St, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR-45062] NR 35 TC 9 Z9 13 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0959-2989 J9 BIO-MED MATER ENG JI Bio-Med. Mater. Eng. PY 2001 VL 11 IS 3 BP 197 EP 207 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 483JW UT WOS:000171633100004 PM 11564903 ER PT J AU Lewandrowski, KU Schollmeier, G Ekkemkamp, A Uhthoff, HK Tomford, WW AF Lewandrowski, KU Schollmeier, G Ekkemkamp, A Uhthoff, HK Tomford, WW TI Incorporation of perforated and demineralized cortical bone allografts. Part II: A mechanical and histologic evaluation SO BIO-MEDICAL MATERIALS AND ENGINEERING LA English DT Article ID YAG LASER ABLATION; OSTEOINDUCTION; TISSUE AB Laser perforated and partially demineralized cortical bone allografts were orthotopically transplanted into sheep tibiae. This paper reports results of the mechanical testing of the transplanted bones, which was done at nine months postoperatively. Animals were divided into three groups of eight according to the type of cortical allograft used: group 1, no treatment; group 2, laser hole grid; and group 3, laser hole grid and partial demineralization. Thus, changes in flexural rigidity of 24 transplanted whole tibiae were investigated. Starting in the anterior direction at the tibial tuberosity, the flexural rigidity was determined using a nondestructive 4-point bending test. The elliptical distribution of the flexural rigidity was compared to the untreated contralateral control bone of each animal. Mechanical parameters were defined as percentage rates for comparative analysis between groups. Flexural rigidity measurement showed that bones transplanted with untreated allografts were stiffer than contralateral control bones. Partial demineralization of allografts reduced the flexural rigidity of transplanted bones below the level of contralateral control bones. Flexural rigidities of test bones transplanted with laser perforated and partially demineralized allografts were higher than those seen in bones transplanted with partially demineralized allografts. These results were corroborated by the histologic analysis which showed that untreated allografts, although surrounded by a periosteal bone cuff that effectively increased their outer diameter. In contrast, excessive bone resorption was observed in partially demineralized allografts. Laser-perforated and partially demineralized allografts showed histologic evidence of complete incorporation into the host bone. Based on this mechanical evaluation, it was concluded that processing of cortical bone allografts by the combination of perforation and partial demineralization resulted in improved mechanical strength of the transplanted bones as compared to processing by partial demineralization alone. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Marzahn Berufsgenossenschatlicher Unfallklin eV, Krankenhaus Berlin, Unfallkrankenhaus Berlin, Klin Unfall & Wiederherstellungschirurg, Berlin, Germany. Ottawa Gen Hosp, Bone & Joint Res Lab, Ottawa, ON K1H 8L6, Canada. RP Lewandrowski, KU (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs, WACC 508,15 Parkman St, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR-45062] NR 15 TC 8 Z9 8 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0959-2989 J9 BIO-MED MATER ENG JI Bio-Med. Mater. Eng. PY 2001 VL 11 IS 3 BP 209 EP 219 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 483JW UT WOS:000171633100005 PM 11564904 ER PT J AU Bernt, K Walker, WA AF Bernt, K Walker, WA TI Human milk and the response of intestinal epithelium to infection SO BIOACTIVE COMPONENTS OF HUMAN MILK SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID HUMAN-BREAST-MILK; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN COLOSTRUM; ESCHERICHIA-COLI; NECROTIZING ENTEROCOLITIS; ANTIBODY-RESPONSES; IN-VITRO; T-CELLS; IMMUNOGLOBULIN PRODUCTION; IMMUNOSUPPRESSIVE FACTOR C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Mucosal Immunol Lab, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. Childrens Hosp, Boston, MA 02129 USA. E Humboldt Univ Berlin, Virchow Clin, D-10099 Berlin, Germany. RP Bernt, K (reprint author), Massachusetts Gen Hosp, Dev Gastroenterol Lab, Boston, MA 02129 USA. RI Bernt, Kathrin/L-1826-2016 OI Bernt, Kathrin/0000-0002-5400-0482 NR 103 TC 8 Z9 8 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 501 BP 11 EP 30 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BU23V UT WOS:000175455800002 PM 11787672 ER PT S AU Papas, KK Colton, CK Gounarides, JS Roos, ES Jarema, MAC Shapiro, MJ Cheng, LL Cline, GW Shulman, GI Wu, HY Bonner-Weir, S Weir, GC AF Papas, KK Colton, CK Gounarides, JS Roos, ES Jarema, MAC Shapiro, MJ Cheng, LL Cline, GW Shulman, GI Wu, HY Bonner-Weir, S Weir, GC BE Hunkeler, D Cherrington, A Prokop, A Rajotte, R TI NMR spectroscopy in beta cell engineering and islet transplantation SO BIOARTIFICIAL ORGANS III: TISSUE SOURCING, IMMUNOISOLATION, AND CLINICAL TRIALS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Bioartificial Organs III - Tissue Sourcing, Immunoisoloation, and Clinical Trials CY OCT 07-11, 2000 CL DAVOS, SWITZERLAND SP Bellevue Asset Management, European Community Cost 840 Encapsulat Network, Fonds Natl Suisse, Inotech Encapsulat AG, Juvenile Diabetes Fdn Int, NIH, Natl Sci Fdn, Nisco Engn, Novartis Pharmaceut Canada Inc, Pronova Biomed, United Engn Fdn DE NMR; islet; beta cell; transportation; transplantation; culture; quality; assessment; c-myc; Bcl-2; LDH; hypoxia; oxygen; lactate; phosphocholine; lipids; apoptosis ID MAGNETIC-RESONANCE SPECTROSCOPY; ENZYME GENE-EXPRESSION; FETAL-RAT ISLETS; INSULIN-SECRETION; PANCREATIC-ISLETS; BIOARTIFICIAL PANCREAS; IN-VITRO; GLUCOSE-METABOLISM; C-MYC; DIABETES-MELLITUS AB Islet transplantation Is a promising method for restoring normoglycemia and alleviating the long term complications of diabetes. Widespread application of Islet transplantation is hindered by the limited supply of human islets and requires a large increase in the availability of suitable insulin secreting tissue as well as robust quality assessment methodologies that can ensure safety and in vivo efficacy. We explore the application of nuclear magnetic resonance (NMR) spectroscopy in two areas relevant to beta cell engineering and Islet transplantation: (1) the effect of genetic alterations on glucose metabolism, and (2) quality assessment of islet preparations prior to transplantation. Results obtained utilizing a variety of NMR techniques demonstrate the following: (1) Transfection of Rat1 cells with the c-myc oncogene (which may be involved in cell proliferation and cell cycle regulation) and overexpression of Bcl-2 (which may protect cells from stresses such as hypoxia and exposure to cytokines) introduce a wide array of alterations in cellular biochemistry, including changes in anaerobic and oxidative glucose metabolism, as assessed by C-13 and P-31 NMR spectroscopy. (2) Overnight incubation of islets and beta cells in the bottom of centrifuge tubes filled with medium at room temperature, as is sometimes done in islet transportation, exposes them to severe oxygen limitations that may cause cell damage. Such exposure, leading to reversible or irreversible damage, can be observed with NMR-detectable markers using conventional C-13 and P-31 NMR spectroscopy of extracts. In addition, markers of irreversible damage (as well as markers of hypoxia) can be detected and quantified without cell extraction using high-resolution magic angle spinning H-1 NMR spectroscopy. Finally, acute ischemia in a bed of perfused beta cells leads to completely reversible changes that can be followed in real time with P-31 NMR spectroscopy. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Novartis Pharmaceut, Analyt & BioNMR, Summit, NJ USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA USA. Yale Univ, Sch Med, New Haven, CT USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Papas, KK (reprint author), MIT, Dept Chem Engn, Room 66-457,77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NIDDK NIH HHS [R01 DK040936] NR 70 TC 25 Z9 25 U1 1 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-342-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 944 BP 96 EP 119 PG 24 WC Engineering, Biomedical; Multidisciplinary Sciences; Transplantation SC Engineering; Science & Technology - Other Topics; Transplantation GA BT69D UT WOS:000173774500009 PM 11797699 ER PT S AU Tramo, MJ Cariani, PA Delgutte, B Braida, LD AF Tramo, MJ Cariani, PA Delgutte, B Braida, LD BE Zatorre, RJ Peretz, I TI Neurobiological foundations for the theory of harmony in Western tonal music SO BIOLOGICAL FOUNDATIONS OF MUSIC SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Biological Foundations of Music CY MAY 20-22, 2000 CL ROCKEFELLER UNIV, NEW YORK, NEW YORK SP Charles A Dana Fdn, David & Lucile Packard Fdn HO ROCKEFELLER UNIV DE consonance; dissonance; harmony; musical; intervals; musical; perception of harmony; psychoacoustics of harmony ID AMPLITUDE-MODULATED SOUNDS; PRIMARY AUDITORY-CORTEX; COMPLEX TONES; AWAKE MONKEY; PITCH; PERCEPTION; CONSONANCE; RESPONSES AB Basic principles of the theory of harmony reflect physiological and anatomical properties of the auditory nervous system and related cognitive systems. This hypothesis is motivated by observations from several different disciplines, including ethnomusicology, developmental psychology, and animal behavior. Over the past several years, we and our colleagues have been investigating the vertical dimension of harmony from the perspective of neurobiology using physiological, psychoacoustic, and neurological methods. Properties of the auditory system that govern harmony perception include (1) the capacity of peripheral auditory neurons to encode temporal regularities in acoustic fine structure and (2) the differential tuning of many neurons throughout the auditory system to a narrow range of frequencies in the audible spectrum. Biologically determined limits on these properties constrain the range of notes used in music throughout the world and the way notes are combined to form intervals and chords in popular Western music. When a harmonic interval is played, neurons throughout the auditory system that are sensitive to one or more frequencies (partials) contained in the interval respond by firing action potentials. For consonant intervals, the fine timing of auditory nerve fiber responses contains strong representations of harmonically related pitches implied by the interval (e.g., Rameau's fundamental bass) in addition to the pitches of notes actually present in the interval. Moreover, all or most of the partials can be resolved by finely tuned neurons throughout the auditory system. By contrast, dissonant intervals evoke auditory nerve fiber activity that does not contain strong representations of constituent notes or related bass notes. Furthermore, many partials are too close together to be resolved. Consequently, they interfere with one another, cause coarse fluctuations in the firing of peripheral and central auditory neurons, and give rise to perception of roughness and dissonance. The effects of auditory cortex lesions on the perception of consonance, pitch, and roughness, combined with a critical reappraisal of published psychoacoustic data on the relationship between consonance and roughness, lead us to conclude that consonance is first and foremost a function of the pitch relationships among notes. Harmony in the vertical dimension is a positive phenomenon, not just a negative phenomenon that depends on the absence of roughness-a view currently held by many psychologists, musicologists, and physiologists. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Tramo, MJ (reprint author), MGH EDR-405,55 Fruit St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC00117, DC02258, DC03054, DC03382] NR 82 TC 88 Z9 88 U1 3 U2 20 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-306-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 930 BP 92 EP 116 PG 25 WC Multidisciplinary Sciences; Psychology SC Science & Technology - Other Topics; Psychology GA BT11G UT WOS:000172009400007 PM 11458869 ER PT J AU Storb, R Blume, KG O'Donnell, MR Chauncey, T Forman, SJ Deeg, HJ Hu, WW Appelbaum, FR Doney, K Flowers, MED Sanders, J Leisenring, W AF Storb, R Blume, KG O'Donnell, MR Chauncey, T Forman, SJ Deeg, HJ Hu, WW Appelbaum, FR Doney, K Flowers, MED Sanders, J Leisenring, W TI Cyclophosphamide and antithymocyte globulin to condition patients with aplastic anemia for allogeneic marrow transplantations: The experience in four centers SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE aplastic anemia; allogeneic marrow grafts; cyclophosphamide and antithymocyte globulin conditioning ID VERSUS-HOST DISEASE; TOTAL-BODY IRRADIATION; MINOR HISTOCOMPATIBILITY ANTIGENS; HLA-MATCHED SIBLINGS; T-CELL ANTIBODIES; ACUTE GRAFT; BLOOD-TRANSFUSIONS; GAMMA-IRRADIATION; MALIGNANT-TUMORS; FANCONI-ANEMIA AB This report summarizes the experience with a conditioning regimen of cyclophosphamide and antithymocyte globulin in patients with severe aplastic anemia given HLA-matched related marrow grafts at 4 transplantation centers. Enrolled were 94 consecutive patients, of whom 87 had received multiple transfusions and 38 had failed immunosuppressive therapy. Their ages ranged from 2 to 59 years. After transplantation, 89 patients received a methotrexate/cyclosporine regimen for graft-versus-host disease (GVHD) prevention. Cyclosporine with or without prednisone was given in 4 patients, and no immunosuppression was given in 1 patient. Ninety-six percent of patients had sustained grafts, whereas 4% rejected grafts between 2 and 7 months after transplantation. Of the 4 rejecting patients, 3 are alive with successful second engraftments. Acute grade II GVHD was seen in 21% of patients, grade III in 7%, and grade IV in 1% of patients. Chronic GVHD was seen in 32% of patients, most of whom responded completely to immunosuppressive therapy. With a median follow-up of 6.0 years (range, 0.5-11.6 years), the survival rate was 88%. No unusual long-term side effects have been seen with the regimen. We conclude that the cyclophosphamide/antithymocyte globulin regimen combined with methotrexate/cyclosporine after transplantation is well tolerated and effective in heavily pretreated patients with aplastic anemia. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Dept Med, Sch Med, Seattle, WA 98195 USA. Univ Washington, Dept Pediat, Sch Med, Seattle, WA 98195 USA. Stanford Univ, Stanford, CA 94305 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Storb, R (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [CA30206, CA49605]; NHLBI NIH HHS [HL36444] NR 50 TC 96 Z9 103 U1 0 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 1 BP 39 EP 44 DI 10.1053/bbmt.2001.v7.pm11215697 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 399YF UT WOS:000166841300006 PM 11215697 ER PT J AU Nikolic, B Khan, A Sykes, M AF Nikolic, B Khan, A Sykes, M TI Induction of tolerance by mixed chimerism with nonmyeloblative host conditioning: The importance of overcoming intrathymic alloresistance SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; monoclonal antibodies; intrathymic alloresistance; tolerance ID BONE-MARROW TRANSPLANTATION; TOTAL LYMPHOID IRRADIATION; ANTIBODY MAB INJECTIONS; WHOLE-BODY IRRADIATION; HEAT-STABLE ANTIGEN; T CELL MABS; THYMIC IRRADIATION; MONOCLONAL-ANTIBODIES; MICE; THYMOCYTES AB A nonmyeloablative conditioning regimen, consisting of depleting doses of anti-CD4 and anti-CDS monoclonal antibodies (MoAbs) given on days -6 and -1 and 3 Gy of whole body irradiation given on day 0, allows the engraftment of fully major histocompatibility complex (MHC)-mismatched allogeneic bone marrow and the induction of tolerance for the graft. IfMoAbs are given on day -5 only, permanent chimerism and tolerance are not observed in most animals. The addition of thymic irradiation to the single MoAb treatment permits tolerance induction in these mice, suggesting that residual host thymocytes reject donor marrow in recipients of 1, but not 2, MoAb injections. In this study, both CD4(+) and CD8(+) thymocytes were found to be responsible for residual alloreactivity in mice receiving only 1 MoAb injection. Go-receptor coating and downmodulation on residual thymocytes occur to a greater extent in recipients of 2 MoAb injections than in recipients of a single MoAb injection. This down-modulation may play a role in the loss of alloreactivity. Our results suggest that a second MoAb injection inactivates mature, functional donor-alloreactive CD4(+) and CD8(+) host thymocytes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Surg Serv, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Surg Serv, Transplantat Biol Res Ctr,Bone Marrow Transplanta, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL49915] NR 27 TC 31 Z9 32 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 3 BP 144 EP 153 DI 10.1053/bbmt.2001.v7.pm11302548 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 416UA UT WOS:000167797500003 PM 11302548 ER PT J AU Ho, VT Weller, E Lee, SJ Alyea, EP Antin, JH Soiffer, RJ AF Ho, VT Weller, E Lee, SJ Alyea, EP Antin, JH Soiffer, RJ TI Prognostic factors for early severe pulmonary complications after hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE pulmonary toxicity; bone marrow transplantation; diffuse alveolar hemorrhage; T-cell depletion; pulmonary function tests ID BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; VERSUS-HOST DISEASE; IDIOPATHIC-PNEUMONIA-SYNDROME; FACTOR ACCELERATES NEUTROPHIL; CHRONIC MYELOGENOUS LEUKEMIA; PLACEBO-CONTROLLED TRIAL; INTERSTITIAL PNEUMONITIS; SINGLE INSTITUTION; DOUBLE-BLIND AB Pulmonary complications are a significant cause of early mortality (before day 100) after bone marrow transplantation (BMT). To identify factors associated with development of early post-BMT severe pulmonary complications (SPCs), we conducted a retrospective review of the medical records of 339 consecutive patients who underwent hematopoietic stem cell transplantation for hematologic disorders and identified pulmonary complications that occurred before day 60 posttransplantation. SPCs, defined as (1) diagnosis of diffuse alveolar hemorrhage, (2) need for mechanical ventilation, or (3) death from respiratory failure, occurred in 48 (24%) of 199 patients receiving allogeneic transplants and 4 (2.9%) of 140 patients receiving autologous transplants (P <.001). Multiple clinical variables were analyzed to determine their influence on the development of SPCs in allogeneic marrow recipients. The method of graft-versus-host disease (GVHD) prophylaxis was the single most important factor affecting SPC incidence. Of patients who received cyclosporine/methotrexate (CYA/MTX) as GVHD prophylaxis, 33% experienced SPCs compared with 8% of those receiving T-cell depletion (TCD) alone (P <.0001). Multivariate analysis confirmed that TCD was associated with a lower risk of SPCs (relative risk [RR], 0.18; P =.0006). In addition to GVHD prophylaxis, a reduced pretransplantation FEV1 (forced expiratory volume in 1 second) (less than or equal to 80% of predicted) was associated with an increased risk for SPCs (odds ratio, 4.4; P =.0025). Grades 2 to 4 acute GVHD, tobacco use, age greater than or equal to 50 years, sex, unrelated donor, cytomegalovirus serologic status, disease status at transplantation, pretransplantation carbon monoxide diffusing capacity, and total body irradiation were not associated with development of SPCs. We conclude that autologous BMT is associated with a significantly lower incidence of SPCs compared with allogeneic BMT and that for allogeneic BMT, GVHD prophylaxis using TCD is associated with a significantly lower risk for SPCs compared with prophylaxis using CYA/MTX. Patients with pretransplantation FEV1 of less than or equal to 80% appear to have a higher risk for SPCs. C1 Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Adult Oncol, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Biostat, 44 Binney St,Rm D1B58, Boston, MA 02115 USA. NR 40 TC 86 Z9 90 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 4 BP 223 EP 229 DI 10.1053/bbmt.2001.v7.pm11349809 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 427YY UT WOS:000168435400005 PM 11349809 ER PT J AU Porter, DL Luger, SM Duffy, KM Stadtmauer, EA Laport, G Schuster, SJ Orloff, G Tsai, D McDaid, K Kathakali, A Leonard, DGB Antin, JH AF Porter, DL Luger, SM Duffy, KM Stadtmauer, EA Laport, G Schuster, SJ Orloff, G Tsai, D McDaid, K Kathakali, A Leonard, DGB Antin, JH TI Allogeneic cell therapy for patients who relapse after autologous stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE allogeneic cell therapy; graft-versus-turner activity; stem cell transplantation ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; DONOR LEUKOCYTE INFUSIONS; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; HOST DISEASE; HODGKINS-DISEASE; ADOPTIVE IMMUNOTHERAPY; CONDITIONING REGIMEN; FLUDARABINE AB Allogeneic donor leukocytes can be used after nonmyeloablative conditioning to exploit their graft-versus-tumor (GVT) activity in the setting of reduced conditioning-regimen toxicity. This approach may be particularly useful for patients who relapse after autologous stem cell transplantation (SCT). However, GVT activity, toxicity, and ability to establish mixed chimerism may differ in patients who were heavily pretreated prior to SCT compared with patients treated earlier in the course of their disease. We have performed a series of studies of nonmyeloablative allogeneic transplantation and present data on the subset of 14 patients treated for relapse after autologous SCT: 4 patients received no conditioning and unstimulated donor leukocyte infusions (DLI), 10 patients received conditioning with fludarabine and cyclophosphamide followed by unstimulated or granulocyte-colony-stimulating factor (G-CSF)-stimulated allogeneic peripheral blood stern cells (PBSCs), 4 patients received no graft-versus-host disease (GVHD) prophylaxis, and 10 patients received cyclosporine GVHD prophylaxis. All but I patient had sustained donor chimerism at least 30 days after allogeneic cell therapy (ACT), and 8 patients had more than 80% donor chimerism after ACT. Acute GVHD developed in 11 patients (grade III-IV: n = 6). Aplasia was more frequent in the patients receiving unstimulated PBSCs, despite the development of mixed chimerism. There were 6 complete responses and 4 partial responses; response was independent of conditioning and growth-factor stimulation of the donor graft. Five patients died of treatment-related causes and 4 patients died from progressive disease. Four patients remained alive 27 to 194 weeks (median, 66 weeks) after ACT. Prior autologous SCT may define a subset of patients at particularly high risk for GVHD and other toxicity after ACT. However, these data show that ACT with either DLI or G-CSF-stimulated blood cells results in direct GVT activity in some patients with Hodgkin's disease, myeloma, and non-Hodgkin's lymphoma, even after relapse from autologous SCT. Most patients developed donor chimerism with minimal conditioning Alternative prophylactic regimens that control GVHD while maintaining GVT are needed to improve outcomes in these heavily pretreated patients. C1 Univ Penn, Med Ctr, Div Hematol Oncol, Bone Marrow & Stem Cell Transplant Program, Philadelphia, PA 19104 USA. Inova Fairfax Bone Marrow Transplant Program, Annandale, VA USA. Univ Penn, Ctr Canc, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Mol Diagnost Core Facil, Philadelphia, PA 19104 USA. Dana Farber Partners Canc Care, Dept Adult Oncol, Boston, MA USA. RP Porter, DL (reprint author), Univ Penn, Med Ctr, Div Hematol Oncol, Bone Marrow & Stem Cell Transplant Program, 16 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. NR 38 TC 34 Z9 34 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 4 BP 230 EP 238 DI 10.1053/bbmt.2001.v7.pm11349810 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 427YY UT WOS:000168435400006 PM 11349810 ER PT J AU Friedberg, JW Neuberg, D Monson, J Jallow, H Nadler, LM Freedman, AS AF Friedberg, JW Neuberg, D Monson, J Jallow, H Nadler, LM Freedman, AS TI The impact of external beam radiation therapy prior to autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE external beam radiation therapy; bone marrow transplantation; non-Hodgkin's lymphoma ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; TOTAL-BODY IRRADIATION; INVOLVED FIELD RADIATION; DIFFUSE ALVEOLAR HEMORRHAGE; ACUTE MYELOGENOUS LEUKEMIA; PHASE I/II TRIAL; TERM FOLLOW-UP; FOLLICULAR LYMPHOMA; LOW-GRADE AB External beam radiation therapy (XRT) is frequently used to treat refractory disease sites or consolidate remission in patients with relapsed non-Hodgkin's lymphoma (NHL) prior to autologous bone marrow transplantation (ABMT). We report the long-term outcome and toxicitics associated with this therapy. We uniformly treated 552 patients with NHL with total body irradiation, high-dose chemotherapy, and anti-B-cell monoclonal antibody-purged ABMT. Of these patients, 152 received XRT to the mediastinum, abdomen, or pelvis (n=102) or other sites (n=50) prior to ABMT. In this nonrandomized series, there was no difference in progression-free survival between patients treated with. XRT and those not treated with XRT. For patients with indolent histology, there was no difference in overall survival between patients treated with XRT and those not treated with XRT. For patients with aggressive histology, the median overall survival time was 64 months in the XRT patients and 79 months in the patients not treated with XRT (P=.09). The risk of acute transplantation-related deaths was not influenced by prior XRT (P=.68). Of patients who received XRT, 12.5% developed secondary myelodysplasia compared with 5.8% of patients not receiving XRT (P=.01). Patients receiving XRT to the mediastinum. or axilla had a significantly higher risk of late respiratory death (P=.002). In conclusion, XRT allows refractory patients to become eligible for transplantation and experience a disease-free survival interval equivalent to that of patients who do not receive XRT. However, a higher incidence of non-relapse-associated deaths was observed in patients who received XRT. Future work should explore alternative conditioning strategies and altered timing of XRT, in an attempt to limit these late toxicities. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Monson, J (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA66996] NR 58 TC 18 Z9 19 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 8 BP 446 EP 453 DI 10.1016/S1083-8791(01)80012-4 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 473NC UT WOS:000171049600005 PM 11569890 ER PT J AU Antin, JH Childs, R Filipovich, AH Giralt, S Mackinnon, S Spitzer, T Weisdorf, D AF Antin, JH Childs, R Filipovich, AH Giralt, S Mackinnon, S Spitzer, T Weisdorf, D TI Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: Recommendations from a Workshop at the 2001 Tandem Meetings SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE lymphohematopoietic chimerism; allogeneic transplantation; restriction fragment length polymorphism ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; CHRONIC MYELOGENOUS LEUKEMIA; MINIMAL RESIDUAL DISEASE; APLASTIC-ANEMIA; MYELOABLATIVE THERAPY; CYTOGENETIC ANALYSIS; VARIABLE NUMBER; REPEAT-MARKERS AB Approaches to the measurement of lymphohematopoietic chimerism. have evolved from laboratory research to important clinical tools. However, there has been no logical, consistent, and uniform set of recommendations for the measurement of chimerism in clinical transplantation. The National Marrow Donor Program and the International Bone Marrow Transplant Registry (IBMTR) sponsored a workshop to discuss the use of chimerism, analysis after allogeneic transplantation. The workshop was organized in an effort to make reasonable recommendations regarding laboratory techniques, the types of specimens to be studied, and the frequency of analysis. The panel recommended the following guidelines: 1. Chimerism. analysis should use sensitive, informative techniques. At present, short tandem repeats (STR) or variable number tandem repeats (VNTR) analysis is the approach most likely to give reproducible informative data. 2. Peripheral blood cells are generally more useful than bone marrow cells for chimerism analysis. 3. Lineage-specific chimerism. should be considered the assay of choice in the setting of nonmyeloablative and reduced-intensity conditioning. 4. The use of T-cell depletion, nonmyeloablative or reduced-intensity conditioning, or novel graft-versus-host disease (GVHD) prophylactic regimens warrants chimerism. analysis at 1, 3, 6, and 12 months, because interventions such as donor lymphocyte infusions may depend on chimerism status. 5. In nonmyeloablative transplantation, the early patterns of chimerism. may predict either GVHD or graft loss. Therefore, more frequent (every 2-4 weeks) peripheral blood analysis may be warranted. 6. For nonmalignant disorders, chimerism. generally should be measured 1, 2, and 3 months after transplantation. Interventions to enhance donor engraftment must be considered on a disease-specific basis in relation to concurrent GVHD and, ultimately, clinical rationale. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. UCL, London, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Antin, JH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jantin@partners.org RI Mackinnon, Stephen/C-5559-2008 NR 39 TC 159 Z9 181 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 9 BP 473 EP 485 DI 10.1053/bbmt.2001.v7.pm11669214 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 480EN UT WOS:000171449200001 PM 11669214 ER PT J AU Dey, BR McAfee, S Sackstein, R Colby, C Saidman, S Weymouth, D Poliquin, C Vanderklish, J Sachs, DH Sykes, M Spitzer, TR AF Dey, BR McAfee, S Sackstein, R Colby, C Saidman, S Weymouth, D Poliquin, C Vanderklish, J Sachs, DH Sykes, M Spitzer, TR TI Successful allogeneic stem cell transplantation with nonmyeloablative conditioning in patients with relapsed hematologic malignancy following autologous stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE nonmyeloablative conditioning; stem cell transplantation; mixed chimerism; graft-versus-tumor effect; donor leukocyte infusion ID BONE-MARROW TRANSPLANTATION; MIXED HEMATOPOIETIC CHIMERISM; NON-HODGKINS-LYMPHOMA; VERSUS-HOST DISEASE; HIGH-DOSE THERAPY; POLYMERASE CHAIN-REACTION; CHRONIC MYELOID-LEUKEMIA; TOTAL-BODY IRRADIATION; MULTIPLE-MYELOMA; ADOPTIVE IMMUNOTHERAPY AB The use of myeloablative preparative therapy and allogeneic stem cell transplantation (alloSCT) as salvage therapy for adult patients with relapsed hematologic malignancy after autologous stem cell transplantation (autoSCT) is generally unsuccessful due to very high treatment-related mortality rates. We evaluated the outcome of HLA-matched related donor alloSCT following nonmyeloablative preparative therapy in 13 patients (median age, 38 years) with relapsed hematologic malignancies (Hodgkin's disease, n = 4; Hodgkin's disease and advanced myelodysplastic syndrome, n = 1; non-Hodgkin's lymphoma, n = 6; multiple myeloma, n = 2) after initial autoSCT Median time from autoSCT to alloSCT was 12 months (range, 3-24 months); 6 patients had chemotherapy-refractory disease following autoSCT, 6 were in untreated relapse, and 1 had a partial response from salvage chemotherapy. Preparative therapy consisted of cyclophosphamide, 150-200 mg/kg; peritransplantation anti-thymocyte globulin; thy mic irradiation (in patients who had not received previous mediastinal irradiation); and a very short course of cyclosporine as GVHD prophylaxis. All patients achieved initial mixed chimerism as defined by greater than 1% donor peripheral white blood cells. Seven patients, who had no evidence of GVI-m, received prophylactic DLI beginning 5 to 6 weeks after transplantation for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft-versus-tumor effect. Six patients showed conversion to full donor chimerism and 1 lost the graft. Grade II or greater acute GVHD occurred in 9 patients. Seven patients achieved a complete response; 6 had no response. The median survival time of the 13 patients is currently 10 months (range, 3-39 months), with an overall survival probability at 2 years of 45% (95% confidence interval [CI], 19%-73%) and a disease-free survival probability at 2 years of 37.5% (95 % CI, 12%-65%). Thus, this novel nonmyeloablative alloSCT strategy followed by prophylactic DLI was well tolerated and can result in durable disease-free survival among patients with advanced hematologic malignancies after a failed autoSCT. Further follow-up and evaluation of additional patients are required to conclusively establish the role of this strategy in the treatment of hematologic malignancies after an autologous transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Program, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Program, Box 640,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [1 RO1 CA79986-O1A1, 1 RO1 CA79988-O1A1] NR 48 TC 47 Z9 50 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 11 BP 604 EP 612 DI 10.1053/bbmt.2001.v7.pm11760148 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 496XX UT WOS:000172424600004 PM 11760148 ER PT J AU Mapara, MY Pelot, M Zhao, GL Swenson, K Pearson, D Sykes, M AF Mapara, MY Pelot, M Zhao, GL Swenson, K Pearson, D Sykes, M TI Induction of stable long-term mixed hematopoietic chimerism following nonmyeloablative conditioning with T cell-depleting antibodies, cyclophosphamide, and thymic irradiation leads to donor-specific in vitro and in vivo tolerance SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; cyclophosphamide; clonal deletion; mixed chimerism; tolerance ID BONE-MARROW TRANSPLANTATION; WHOLE-BODY IRRADIATION; LARGE-ANIMAL-MODEL; ALLOGRAFT TOLERANCE; LYMPHOHEMATOPOIETIC CHIMERISM; ALLOGENEIC CHIMERISM; PREPARATIVE REGIMEN; CLONAL DELETION; MINIATURE SWINE; MAB INJECTIONS AB Background: Successful transplantation of solid organs relies on long-term immunosuppression for the prevention of graft rejection. Donor-specific tolerance without the need for continuous immunosuppression can he observed after allogeneic BMT. However, its routine use for tolerance induction has been precluded so far by the high conditioning-related toxicity of standard BMT regimens. Our laboratory has recently established a cyclophosphamide (CTX) plus thymic irradiation (TI)-based nonmyeloablative conditioning protocol for the treatment of hematologic malignancies. We have recently described the successful clinical application of this approach for the induction of donor-specific tolerance in a patient receiving a living-related kidney transplant, which resulted in graft acceptance without long-term immunosuppression. The aim of this study was to evaluate the induction and maintenance of host-versus-graft tolerance following this CTX-plus-TI-based regimen in a mouse model. Methods: Induction of mixed hematopoietic chimerism and development of donor-specific tolerance following the CTX-based nonmyeloablative conditioning regimen (200 mg/kg CTX, in vivo T-cell depletion [anti-CD4 monoclonal antibody (MoAb) GK1.5 and anti-CD8 MoAb 2.43], and 7 Gy TI) was studied in the fully major histocompatibility complex (MHC)-mismatched B10A (H2(a))--> B6 (H2(b)) strain combination. Results. The conditioning regimen allowed allogeneic bone marrow engraftment and persistent (>30 weeks) mixed lymphohematopoietic chimerism in almost all recipients. TI was essential to allow engraftment and development of tolerance, which was evident in all lasting chimeras. Compared to animals receiving a similar TBI-based conditioning regimen, overall levels of chimerism. were significantly lower in the CTX-plus-TI-conditioned animals. However, donor-specific tolerance in vitro and in vivo was evident in CTX-plus-TI-conditioned chimeras. Tolerance was associated with the presence of donor-type MHC class II+ cells in the thymus and deletion of donor-reactive cells, as determined by Mtv-8 and Mtv-9 superantigen-mediated deletion of V beta 11(+) and V beta5/1.2(+) T cells. Conclusion: Engraftment, long-term chimerism, and induction of donor-specific tolerance can be achieved using a nonmyeloablative CTX-based conditioning regimen in fully NMC-mismatched BMT recipients without the induction of GVHD. C1 Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Massachusetts Gen Hosp,Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Massachusetts Gen Hosp,Sch Med, MGH E Bldg 149-5102, Boston, MA 02129 USA. RI mapara, markus/A-2134-2013 FU NCI NIH HHS [R01 CA79989] NR 32 TC 39 Z9 41 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 12 BP 646 EP 655 DI 10.1053/bbmt.2001.v7.pm11787527 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 507XN UT WOS:000173056700002 PM 11787527 ER PT J AU Pru, JK Hendry, IR Davis, JS Rueda, BR AF Pru, JK Hendry, IR Davis, JS Rueda, BR TI Fas-mediated activation of the sphingomyelin pathway in bovine steroidogenic luteal cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA USA. Womens Res Inst, Wichita, KS USA. Univ Kansas, Sch Med, Wichita, KS 67214 USA. VA Med Ctr, Wichita, KS USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 198 EP 198 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900286 ER PT J AU Pastor-Soler, NM Fisher, J Sharpe, RM Bagnis, C Van Hoek, A Brown, D Breton, S AF Pastor-Soler, NM Fisher, J Sharpe, RM Bagnis, C Van Hoek, A Brown, D Breton, S TI Hormonal regulation of aquaporin 9 expression in the rat epididymis during postnatal development. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. MRC, Ctr Reprod Biol, Reprod Biol Unit, Edinburgh EH3 9EW, Midlothian, Scotland. Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Sharpe, Richard/D-2725-2013 OI Sharpe, Richard/0000-0003-1686-8085 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 225 EP 225 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900355 ER PT J AU Carambula, SF Matikainen, T Flavell, RA Tilly, JL Rueda, BR AF Carambula, SF Matikainen, T Flavell, RA Tilly, JL Rueda, BR TI Caspase 3 serves as a pivitol mediator of luteal regression in vivo. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 240 EP 241 PG 2 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900394 ER PT J AU Cavicchio, VA Pru, JK Davis, JS Rueda, BR Townson, DH AF Cavicchio, VA Pru, JK Davis, JS Rueda, BR Townson, DH TI Regulation of monocyte chemoattractant protein-1 (MCP-1) by pro-inflammatory cytokines in endothelial cells of the bovine corpus luteum. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ New Hampshire, Dept Anim & Nutr Sci, Durham, NH 03824 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. Univ Kansas, Sch Med, VA Med Ctr, Womens Res Inst, Wichita, KS 67214 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 240 EP 240 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900393 ER PT J AU Jurisicova, A Oh, JM Perez, GI Tilly, JL AF Jurisicova, A Oh, JM Perez, GI Tilly, JL TI Aromatic hydrocarbon receptor activation induces apoptosis in murine preimplantation embryos. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Obstet & Gynecol, Toronto, ON, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 261 EP 261 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900445 ER PT J AU Perez, GI Tilly, JL AF Perez, GI Tilly, JL TI Gap junctional communication is required for accelerated rates of oocyte apoptosis induced by advancing maternal age but not by chemotherapy. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 261 EP 261 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900446 ER PT J AU Acton, BM Jurisicova, A Ahmady, A Xu, J Perez, GI Casper, RF AF Acton, BM Jurisicova, A Ahmady, A Xu, J Perez, GI Casper, RF TI Microinjection of mitochondrial fractions into FVB oocytes influences in vitro survival rates. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ Toronto, Samuel Lunenfeld Res Inst, Dept Ob Gyn, MSH, Toronto, ON, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 279 EP 279 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900492 ER PT J AU Townson, DH Cavicchio, VA Pru, JK Hendry, IR Davis, JS Rueda, BR AF Townson, DH Cavicchio, VA Pru, JK Hendry, IR Davis, JS Rueda, BR TI Monocyte chemoattractant protein-1 (MCP-1) in the bovine corpus luteum: Regulation by cytokines in luteal cell cultures containing endothelial cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ New Hampshire, Dept Anim & Nutr Sci, Durham, NH 03824 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Kansas, Sch Med, Womens Res Inst, VA Med Ctr, Wichita, KS USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 287 EP 288 PG 2 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900514 ER PT S AU Soukos, NS Hamblin, MR Deutsch, TF Hasan, T AF Soukos, NS Hamblin, MR Deutsch, TF Hasan, T BE Bearman, GH Bornhop, DJ Levenson, RM TI Monoclonal antibody-tagged receptor-targeted contrast agents for detection of cancers SO BIOMARKERS AND BIOLOGICAL SPECTRAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biomarkers and Biological Spectral Imaging CY JAN 23, 2001 CL SAN JOSE, CA SP USAF Off Sci Res, SPIE DE fluorescence diagnosis; oral pre-cancer; hamster cheek pouch; photodynamic therapy; photoimmunotherapy; carcinogenesis ID EPIDERMAL-GROWTH-FACTOR; FLUOROCHROME-LABELED ANTIBODIES; SQUAMOUS-CELL CARCINOMA; HAMSTER BUCCAL POUCH; NUDE-MICE; CARCINOEMBRYONIC ANTIGEN; SOLID TUMORS; PHASE-I; FLUORESCENCE; LESIONS AB Oral cancer and precancer overexpress the epidermal growth factor receptor (EGFR) and monoclonal antibodies against EGFR coupled to photoactive dyes may have a potential both as diagnostic and treatment modalities for oral premalignancy. We asked whether an anti-EGFR Mab (C225) conjugated with the fluorescent dye indocyanine Cy5.5 could detect dysplastic changes in the hamster cheek pouch carcinogenesis model. Secondly, we tested whether the same antibody conjugated with the photosensitizer chlorin(e6) could be used together with illumination to reduce levels of expression of EGFR as evaluated by the immunophotodetection procedure. Increased fluorescence appeared to correlate with development of premalignancy when the C225-Cy5.5 conjugate was used. Areas with increased fluorescence signal were found in carcinogen-treated but clinically normal cheek pouches, that revealed dysplastic changes by histology. The immunophotodetection procedure was carried out after photoimmunotherapy with the C225-ce6 conjugate, and showed a significant reduction in fluorescence in the illuminated compared to non-illuminated areas in the carcinogen-treated but not the normal cheek pouch. The results demonstrate that the use of anti-EGFR Mab targeted photoactive dyes may serve as a feedback controlled optical diagnosis and therapy procedure for oral premalignant lesions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. EM soukos@helix.mgh.harvard.edu; hamblin@helix.mgh.harvard.edu; deutsch@helix.mgh.harvard.edu; hasan@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 38 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3937-1 J9 PROC SPIE PY 2001 VL 4259 BP 115 EP 128 DI 10.1117/12.432490 PG 14 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BT01W UT WOS:000171643400017 ER PT J AU Arystarkhova, E Asinovski, NK Wetzel, RK Sweadner, KJ AF Arystarkhova, E Asinovski, NK Wetzel, RK Sweadner, KJ TI Regulation of renal Na,K-ATPase by the gamma subunit: Functional consequences of expression of splice variants SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 163 BP 37A EP 37A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200172 ER PT J AU Donnet, C Arystarkhova, E Sweadner, KJ AF Donnet, C Arystarkhova, E Sweadner, KJ TI Thermal denaturation of the Na,K-ATPase: Evidence for alpha-alpha oligomeric interation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 162 BP 37A EP 37A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200171 ER PT J AU Lee, KH Wucherpfennig, KW Wiley, DC AF Lee, KH Wucherpfennig, KW Wiley, DC TI Crystal structure of HLA-DQ8: Human MHC class II molecules associated with susceptibility to type I diabetes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Childrens Hosp, Howard Hughes Med Inst, Mol Med Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 266 BP 60A EP 60A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200275 ER PT J AU Menard, C Ranganathan, R Horvitz, HR Cannon, SC AF Menard, C Ranganathan, R Horvitz, HR Cannon, SC TI Anion permeation and M2-dependent selectivity of MOD-1, A c.elegans serotonin-gated chloride channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 462 BP 102A EP 102A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200471 ER PT J AU Raines, DE Claycomb, RJ Scheller, M Forman, SA AF Raines, DE Claycomb, RJ Scheller, M Forman, SA TI Nonhalogenated alkane anesthetics fail to potentiate agonist actions on two ligand-gated ion channels at clinically relevant concentrations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 464 BP 103A EP 103A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200473 ER PT J AU Scheller, M Forman, SA AF Scheller, M Forman, SA TI Two mutations in the GABA(A)R pore domain selectively alter deactivation and desensitization rates SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Tech Univ Munich, Klinikum Rechts Isar, D-8000 Munich, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 483 BP 107A EP 107A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200492 ER PT J AU Ranganathan, R Cannon, SC Horvitz, HR AF Ranganathan, R Cannon, SC Horvitz, HR TI A serotonin-gated chloride channel mediates experience-dependent modulation of C-elegans behavior. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 489 BP 109A EP + PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200498 ER PT J AU Migliorini, C Yuan, J Jain, RK Munn, LL AF Migliorini, C Yuan, J Jain, RK Munn, LL TI Erythrocyte mediated leukocyte endothelial wall interactions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 645 BP 145A EP 145A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200667 ER PT J AU Oh, KJ Zha, J Weiler, S Korsmeyer, SJ AF Oh, KJ Zha, J Weiler, S Korsmeyer, SJ TI A novel post translational N-myristoylation of BID promotes targeting to mitochondria and apoptotic activity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1029 BP 253A EP 254A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201162 ER PT J AU Addona, GH Husain, SS Miller, KW AF Addona, GH Husain, SS Miller, KW TI The topography of an anesthetic binding site in adenylate kinase using photoreactive anesthetics and mass spectrometry SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1311 BP 314A EP 315A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201442 ER PT J AU Burton, K Jain, RK Boucher, Y AF Burton, K Jain, RK Boucher, Y TI Traction forces and migration in cancer, endothelial, and fibroblast cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1439 BP 343A EP 343A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201571 ER PT J AU Cantiello, HF Burns, ND Lader, AS AF Cantiello, HF Burns, ND Lader, AS TI Characterization of ATP transport mechanisms in Caco-2 intestinal cells. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp East, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2018 BP 473A EP 473A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202151 ER PT J AU Carattino, MD Timpanaro, G Damiano, A Catanzaro, OL Cantiello, HF AF Carattino, MD Timpanaro, G Damiano, A Catanzaro, OL Cantiello, HF TI Actin filament organization controls epithelial sodium channels from mouse renal cortex. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UBA, Lab Canales Ion, Dept Quim Analit & Fisicoquim, FFyB, Buenos Aires, DF, Argentina. CONICET, PROSIVAD, Buenos Aires, DF, Argentina. Massachusetts Gen Hosp East, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2022 BP 473A EP 474A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202155 ER PT J AU Godoy, S Piantino, J Ibarra, C Cantiello, HF Kotsias, BA AF Godoy, S Piantino, J Ibarra, C Cantiello, HF Kotsias, BA TI Membrane currents recorded in oocytes of the toad Bufo arenarum. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Buenos Aires, Fac Med, Dept Fisiol, RA-1425 Buenos Aires, DF, Argentina. Univ Buenos Aires, Inst Invest Med Alfredo Lanari, Buenos Aires, DF, Argentina. Massachusetts Gen Hosp East, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2023 BP 474A EP 474A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202156 ER PT J AU Sweadner, KJ Donnet, C Arystarkhova, E Feschenko, MS AF Sweadner, KJ Donnet, C Arystarkhova, E Feschenko, MS TI Predicted structure of Na,K-ATPase based on Ca ATPase structure and thermal denaturation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2144 BP 501A EP 501A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202277 ER PT J AU Melder, RJ Kristensen, CA Munn, LL Jain, RK AF Melder, RJ Kristensen, CA Munn, LL Jain, RK TI Modulation of A-NK cell rigidity: In vitro characterization and in vivo implications for cell delivery SO BIORHEOLOGY LA English DT Article DE activated lymphocyte; rigidity; deformability; thioglycollate ID ACTIVATED KILLER-CELLS; ENDOTHELIAL GROWTH-FACTOR; ADOPTIVELY TRANSFERRED ADHERENT; INDUCED LEUKOCYTE ADHESION; MICE; KINETICS; INVIVO; TUMORS; MICROCIRCULATION; ANGIOGENESIS AB The delivery of cells to specific regions of the vasculature is a critical step in many therapeutic strategies. These include the packaging of DNA or RNA in cell "vehicles" for delivery to tissues, the reconstitution of differentiated cells to an organ using embryonic stem cells, and the enhancement of the immune response using effector lymphocytes. In most cases, these cells must be injected systemically. Unfortunately, ex vivo manipulation or activation can affect cell visco-elastic properties, making it difficult for the injected cells to traverse capillary beds. Compounding the problem is the fact that common agents used in the laboratory for increasing cell deformability generally have adverse side effects on the therapeutic potential of the cells. Using micropipet aspiration techniques, cytotoxicity assays and in vivo trafficking studies we show that: (1) the rigidity of injected effector cells directly affects resistance to passage through tissue; (2) modulation of cytoskeletal organization can be used to decrease cell rigidity, but can also compromise therapeutic efficacy; and (3) thioglycollate, an agent which does not influence effector lymphocyte cytotoxic activity, reduces cell rigidity and entrapment in the lungs. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat, 100 Blossom St,Cox 7, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R35 CA 56591, P01 CA80124]; NHLBI NIH HHS [R01 HL64240] NR 38 TC 6 Z9 6 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0006-355X J9 BIORHEOLOGY JI Biorheology PY 2001 VL 38 IS 2-3 BP 151 EP 159 PG 9 WC Biophysics; Engineering, Biomedical; Hematology SC Biophysics; Engineering; Hematology GA 456DC UT WOS:000170067000008 PM 11381172 ER PT J AU Roumiantsev, S de Aos, IE Varticovski, L Ilaria, RL Van Etten, RA AF Roumiantsev, S de Aos, IE Varticovski, L Ilaria, RL Van Etten, RA TI The Src homology 2 domain of Bcr/Abl is required for efficient induction of chronic myeloid leukemia-like disease in mice but not for lymphoid leukemogenesis or activation of phosphatidylinositol 3-kinase SO BLOOD LA English DT Article ID BCR-ABL ONCOGENE; TRANSFORMED HEMATOPOIETIC-CELLS; KINASE-ACTIVITY; SH2 DOMAIN; TYROSINE PHOSPHORYLATION; SIGNALING PATHWAYS; C-MYC; GROWTH; P210; P210(BCR/ABL) AB The effect of mutations in the Src homology 2 (SH2) domain of the BCR/ABL oncogene on leukemogenesis was tested in a quantitative murine bone marrow transduction/transplantation assay that accurately models human Philadelphia-positive B-lymphoid leukemia and chronic myeloid leukemia (CML), The SH2 domain was not required for induction of B-lymphoid leukemia in mice by BCR/ABL, Under conditions where the p190 end p210 forms of BCR/ABL induce fatal CML-like myeloproliferative disease within 4 weeks, p210 SH2 mutants induced CML-like disease in some mice only after a significant delay, with other recipients succumbing to B-lymphoid leukemia instead. In contrast, p190 BCR/ABL SH2 point and deletion mutants rapidly induced CML-like disease, These results provide the first direct evidence of significant differences in cell signaling by the Bcr/Abl tyrosine kinase between these distinct leukemias, Contrary to previous observations, high levels of phosphatidylinositol 3-kinase (PI 3-kinase) activity in primary malignant lymphoblasts end myeloid cells from recipients of marrow transduced with the BCR/ABL SH2 mutants were found, Hence, the decreased induction of CML-like disease by the p210 BCR/ABL SH2 mutants is not due to impaired activation of PI 3-kinase. (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, Boston, MA 02115 USA. Tufts Univ, St Elizabeths Hosp, Sch Med, Dept Biomed Res, Boston, MA 02135 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA94536, CA57593]; NHLBI NIH HHS [HL03310] NR 36 TC 69 Z9 74 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 JAN 1 PY 2001 VL 97 IS 1 BP 4 EP 13 DI 10.1182/blood.V97.1.4 PG 10 WC Hematology SC Hematology GA 388JL UT WOS:000166177300001 PM 11133737 ER PT J AU Mao, XH Fujiwara, Y Chapdelaine, A Yang, HD Orkin, SH AF Mao, XH Fujiwara, Y Chapdelaine, A Yang, HD Orkin, SH TI Activation of EGFP expression by Cre-mediated excision in a new ROSA26 reporter mouse strain SO BLOOD LA English DT Article ID GENE; MICE; RECOMBINATION; CELLS AB Reporter mouse strains are important tools for monitoring Cre recombinase-mediated excision in vivo. In practice, excision may be incomplete in a given population due to threshold level or variegated expression of Cre, Hence, it is desirable in many experimental contexts to isolate cells that have undergone excision to assess the consequences of gene ablation, To generate alternative reporter mice, an enhanced green fluorescent protein (EGFP) gene was targeted to the retroviral-trapped ROSA26 locus, Upon Cre-mediated excision of "Stop" sequences, EGFP was expressed ubiquitously during embryogenesis and in adult tissues (including T cells, B cells, and myeloid cells). Using this new reporter strain, separation of excised from nonexcised cells in vitro was achieved in thymocytes in a noninvasive manner based on activated EGFP expression. This new EGFP reporter strain should facilitate a variety of conditional gene-targeting experiments, including the functional studies of hematopoietic cells in lineage-specific knockout mice. (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Div Hematol Oncol, Boston, MA 02115 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. RP Orkin, SH (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Div Hematol Oncol, Boston, MA 02115 USA. NR 10 TC 180 Z9 185 U1 1 U2 12 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2001 VL 97 IS 1 BP 324 EP 326 DI 10.1182/blood.V97.1.324 PG 3 WC Hematology SC Hematology GA 388JL UT WOS:000166177300042 PM 11133778 ER PT J AU Paw, BH AF Paw, BH TI Cloning of the zebrafish retsina blood mutation: A genetic model for dyserythropoiesis and erythroid cytokinesis SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article ID POSITIONAL CLONING; DANIO-RERIO; HEMATOPOIESIS; GENOME; MAP; DISEASE; LIBRARY; CLOCHE C1 Childrens Hosp, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Paw, BH (reprint author), Childrens Hosp, Div Hematol, 320 Longwood Ave,Enders 7, Boston, MA 02115 USA. NR 25 TC 9 Z9 9 U1 1 U2 2 PU ACADEMIC PRESS INC 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 JAN PY 2001 VL 27 IS 1 BP 62 EP 64 DI 10.1006/bcmd.2000.0354 PG 3 WC Hematology SC Hematology GA 415TG UT WOS:000167738300005 PM 11358361 ER PT J AU Neufeld, EJ Fleming, JC Tartaglini, E Steinkamp, MP AF Neufeld, EJ Fleming, JC Tartaglini, E Steinkamp, MP TI Thiamine-responsive megaloblastic anemia syndrome: A disorder of high-affinity thiamine transport SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article ID GENE; MUTATIONS; DEAFNESS; SLC19A2 AB Thiamine-responsive megaloblastic anemia (TRMA) syndrome (OMIM No. 249270) comprises a distinctive triad of clinical features: megaloblastic anemia with ringed sideroblasts, diabetes mellitus, and progressive sensorineural deafness. The TRMA gene has been mapped and cloned. Designated "SLC19A2" as a member of the solute carrier gene superfamily, this gene is mutated in all TRMA kindreds studied to date. The product of the SLC19A2 gene is a membrane protein which transports thiamine (vitamin BI) with sub-micromolar affinity. Cells from TRMA patients are uniquely sensitive to thiamine depletion to the nanomolar range, while pharmacologic doses of vitamin B1 ameliorate the anemia and diabetes. Here we review the current status of studies aimed at understanding the pathophysiology of this unique transport defect, (C) 2001 Academic Press. C1 Childrens Hosp, Div Hematol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Div Hematol, Dana Farber Canc Inst, 300 Longwood Ave, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011; OI Steinkamp, Mara/0000-0003-1226-9325 NR 22 TC 51 Z9 53 U1 0 U2 1 PU ACADEMIC PRESS INC 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 JAN PY 2001 VL 27 IS 1 BP 135 EP 138 DI 10.1006/bcmd.2000.0356 PG 4 WC Hematology SC Hematology GA 415TG UT WOS:000167738300017 PM 11358373 ER PT J AU Abraham, EH Shrivastav, B Salikhova, AY Sterling, KM Johnston, N Guidotti, G Scala, S Litman, T Chan, KC Arceci, RJ Steiglitz, K Herscher, L Okunieff, P AF Abraham, EH Shrivastav, B Salikhova, AY Sterling, KM Johnston, N Guidotti, G Scala, S Litman, T Chan, KC Arceci, RJ Steiglitz, K Herscher, L Okunieff, P TI Cellular and biophysical evidence for interactions between adenosine triphosphate and P-glycoprotein substrates: functional implications for adenosine triphosphate/drug cotransport in P-glycoprotein overexpressing tumor cells and in P-glycoprotein low-level expressing erythrocytes SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE erythrocyte; RBC; ATP (adenosine triphosphate); MDR (multidrug resistance protein); Pgp (P-glycoprotein); CD39; apyrase; ATP transporter; cotransport; plasma ATP; Pgp drug substrates; doxorubicin; adriamycin; verapamil; colchicine; electrophoresis; capillary electrophoresis; knockout mice; Taxol; camptothecin; stoichiometry of coupling; ABC proteins ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CAPILLARY-ZONE-ELECTROPHORESIS; MULTIDRUG-RESISTANCE; ATP CHANNEL; DOXORUBICIN ADRIAMYCIN; DRUG-RESISTANCE; TRANSPORT; ASSOCIATION; MECHANISM; CFTR AB P-glycoprotein is involved with the removal of drugs, most of them cations, from the plasma membrane and cytoplasm. Pgp is also associated with movement of ATP, an anion, from the cytoplasm to the extracellular space. The central question of this study is whether drug and ATP transport associated with the expression of Pgp are in any way coupled. We have measured the stoichiometry of transport coupling between drug and ATP release. The drug and ATP transport that is inhibitable by the sulfonylurea compound, glyburide (P. E. Golstein, A. Boom, J. van Geffel, P. Jacobs, B. Masereel, and R. Beauwens, Pfluger's Arch. 437, 652, 1999), permits determination of the transport coupling ratio, which is close to 1:1. In view of this result, we asked whether ATP interacts directly with Pgp substrates. We show by measuring the movement of Pgp substrates in electric fields that ATP and drug movement are coupled. The results are compatible with the view that substrates for Pgp efflux are driven by the movement of ATP through electrostatic interaction and effective ATP-drug complex formation with net anionic character. This mechanism not only pertains to drug efflux from tumor cells overexpressing Pgp, but also provides a framework for understanding the role of erythrocytes in drug resistance. The erythrocyte consists of a membrane surrounding a millimolar pool of ATP. Mammalian RBCs have no nucleus or DNA drug/toxin targets. From the perspective of drug/ATP complex formation, the RBC serves as an important electrochemical sink for toxins. The presence in the erythrocyte membrane of approximately 100 Pgp copies per RBC provides a mechanism for eventual toxin clearance. The RBC transport of toxins permits their removal from sensitive structures and ultimate clearance from the organism via the liver and/or kidneys. (C) 2001 Academic Press. C1 Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA. NCI, Div Clin Sci, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Radiat Oncol Branch, Bethesda, MD 20892 USA. Harvard Univ, Dept Biochem & Mol Biol, Cambridge, MA 02138 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Analyt Chem Lab, SAIC Frederick, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. Univ Rochester, Ctr Canc, Dept Radiat Oncol, Rochester, NY 14642 USA. RP Abraham, EH (reprint author), Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA. RI Scala, Stefania/K-1380-2016 OI Scala, Stefania/0000-0001-9524-2616 NR 68 TC 18 Z9 19 U1 0 U2 4 PU ACADEMIC PRESS INC 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 JAN PY 2001 VL 27 IS 1 BP 181 EP 200 DI 10.1006/bcmd.2000.0373 PG 20 WC Hematology SC Hematology GA 415TG UT WOS:000167738300023 PM 11358379 ER PT J AU Van Etten, RA AF Van Etten, RA TI Retroviral transduction models of Ph+ leukemia: Advantages and limitations for modeling human hematological malignancies in mice SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL; MYELOPROLIFERATIVE DISEASE; TRANSGENIC MICE; C-ABL; GENE; INDUCTION; CELL; P190; P210 AB There are two commonly used approaches to modeling human leukemia in mice: generation of mutant mice by traditional transgenic or knock-out/knock-in methods and retroviral bone marrow transduction and transplantation. For modeling leukemia, the retroviral model system has some distinct advantages over transgenic mice. Testing different forms and mutants of a given oncogene is much easier with the retroviral system and avoids the potential deleterious effects of expression of a transgene in nonhematopoietic tissues and during development. The retroviral provirus serves as a clonal marker of a transduced cell, facilitating analysis of clonality and transplantability of the malignancy. Finally, the retroviral system allows the assessment of the action of an oncogene in different subsets of hematopoietic precursor cells in the bone marrow, which is difficult or impossible with transgenic models. This article summarizes recent progress in modeling human Philadelphia-positive leukemia in mice with the retroviral bone marrow transduction/transplantation system and emphasizes the advantages and limitations of this approach with examples from the BCR-ABL leukemogenesis literature. (C) 2001 Academic Press. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA57593] NR 21 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC 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 JAN PY 2001 VL 27 IS 1 BP 201 EP 205 DI 10.1006/bcmd.2000.0370 PG 5 WC Hematology SC Hematology GA 415TG UT WOS:000167738300024 PM 11358380 ER PT S AU Sheridan, AM Bonventre, JV AF Sheridan, AM Bonventre, JV BE Ronco, C Bellomo, R LaGreca, G TI Pathophysiology of ischemic acute renal failure SO BLOOD PURIFICATION IN INTENSIVE CARE SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Article; Proceedings Paper CT 2nd International Course on Critical Care Nephrology CY MAY 22-25, 2001 CL VICENZA, ITALY ID ENDOTHELIN-RECEPTOR ANTAGONIST; TUBULAR EPITHELIAL-CELLS; NITRIC-OXIDE; REPERFUSION INJURY; POSTISCHEMIC INJURY; RAT-KIDNEY; ISCHEMIA/REPERFUSION INJURY; PHOSPHOLIPASE A(2); PROXIMAL TUBULES; UP-REGULATION C1 Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp, Med Serv, 149-4002 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 39773, DK 54741, DK 38452]; NINDS NIH HHS [NS 10828] NR 97 TC 65 Z9 66 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 3-8055-7207-7 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2001 VL 132 BP 7 EP 21 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA BS88G UT WOS:000171313000002 PM 11395913 ER PT J AU Kolesnikova, TV Mannion, BA Berditchevski, F Hemler, ME AF Kolesnikova, Tatiana V. Mannion, Brian A. Berditchevski, Fedor Hemler, Martin E. TI beta 1 integrins show specific association with CD98 protein in low density membranes SO BMC BIOCHEMISTRY LA English DT Article AB Background: The CD98 (4F2, FRP-1) is a widely expressed cell surface protein heterodimer composed of a glycosylated heavy chain and a non-glycosylated light chain. Originally described as a T cell activation antigen, it was later shown to function in amino acid transport, cell fusion and homotypic cell aggregation. Several lines of evidence suggest its functional interaction with integrins but the biochemical basis for this interaction has been unclear. Results: We demonstrate that CD98 constitutively and specifically associates with beta 1 integrins (alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1 and alpha 6 beta 1), but minimally with alpha 4 beta 1. Integrin-CD98 association was established by reciprocal immunoprecipitation experiments, and confirmed by CD98-induced clustering of alpha 3 beta 1 but not alpha 4 beta 1 on the surface of rhabdomyosarcoma cells. Integrin-CD98 association is independent of the a subunit cytoplasmic tail, is maintained in alpha 3 beta 1 ligand-interaction deficient mutants, and is not inhibited by EDTA. Within the CD98 heavy chain, a C109S mutation (but not a C330S mutation) caused a loss of beta 1 integrin association. The same C109S mutation also caused a loss of CD98 light chain association. Importantly, CD98 associated selectively with beta 1 integrins present in low density "light membrane" fractions on a sucrose gradient. CD98 was not present in dense fractions that contained the majority of beta 1 integrins. Notably, the C109S mutant of CD98, that did not associate with beta 1 integrins, showed also a reduced localization into light membrane fractions. Conclusions: We demonstrate that CD98 association with beta 1 integrins is specific, occurs in the context of low density membranes, and may require the CD98 light chain. C1 [Kolesnikova, Tatiana V.; Hemler, Martin E.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Mannion, Brian A.] Cincinnati Hematol Oncol Inc, Cincinnati, OH 45209 USA. [Berditchevski, Fedor] Univ Birmingham, CRC Inst Canc Studies, Birmingham B15 2TA, W Midlands, England. RP Hemler, ME (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM Tatiana_Kolesnikova@DFCI.HARVARD.EDU; bmannion@cinci.rr.com; F.Berditchevski@bham.ac.uk; Martin_Helmer@DFCI.Harvard.EDU FU National Institutes of Health [CA42368, CA71740-02]; Leukemia and Lymphoma Society; Lady TATA postdoctoral fellowship FX We thank Dr. Jeffrey Leiden for CD98 cDNA. This work was supported by National Institutes of Health grants CA42368 (to M.E.H.) and CA71740-02 (to B.A.M.), Leukemia and Lymphoma Society postdoctoral fellowship (to T.V.K.) and a Lady TATA postdoctoral fellowship (to F.B.) NR 60 TC 43 Z9 44 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2091 J9 BMC BIOCHEM JI BMC Boichem. PY 2001 VL 2 AR 10 DI 10.1186/1471-2091-2-10 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34NA UT WOS:000209091900010 PM 11696247 ER PT J AU Savage, CR Deckersbach, T Heckers, S Wagner, AD Schacter, DL Alpert, NM Fischman, AJ Rauch, SL AF Savage, CR Deckersbach, T Heckers, S Wagner, AD Schacter, DL Alpert, NM Fischman, AJ Rauch, SL TI Prefrontal regions supporting spontaneous and directed application of verbal learning strategies - Evidence from PET SO BRAIN LA English DT Article DE positron emission tomography; episodic memory; semantic organization; prefrontal cortex; orbitofrontal cortex ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; FRONTAL-LOBE DAMAGE; ORBITOFRONTAL CORTEX; EPISODIC MEMORY; WORKING-MEMORY; ORGANIZATIONAL STRATEGIES; PARKINSONS-DISEASE; DECISION-MAKING; FUNCTIONAL MRI AB The prefrontal cortex has been implicated in strategic memory processes, including the ability to use semantic organizational strategies to facilitate episodic learning. An important feature of these strategies is the way they are applied in novel or ambiguous situations-failure to initiate effective strategies spontaneously in unstructured settings is a central cognitive deficit in patients with frontal lobe disorders. The current study examined strategic memory with PET and a verbal encoding paradigm that manipulated semantic organization in three encoding conditions: spontaneous, directed and unrelated. During the spontaneous condition, subjects heard 24 words that were related in four categories but presented in mixed order, and they were not informed of this structure beforehand. Any semantic reorganization was, therefore, initiated spontaneously by the subject. In the directed condition, subjects were given a different list of 24 related words and explicitly instructed to notice relationships and mentally group related words together to improve memory. The unrelated list consisted of 24 unrelated words. Behavioural measures included semantic clustering, which assessed active regrouping of words into semantic categories during free recall. In graded PET contrasts (directed > spontaneous > unrelated), two distinct activations were found in left inferior prefrontal cortex (inferior frontal gyrus) and left dorsolateral prefrontal cortex (middle frontal gyrus), corresponding to levels of semantic clustering observed in the behavioural data. Additional covariate analyses in the first spontaneous condition indicated that blood how in orbitofrontal cortex (OFC) was strongly correlated with semantic clustering scores during immediate free recall. Thus, blood how in OFC during encoding predicted which subjects would spontaneously initiate effective strategies during free recall. Our findings indicate that OFC performs an important, and previously unappreciated, role in strategic memory by supporting the early mobilization of effective behavioural strategies in novel or ambiguous situations. Once initiated, lateral regions of left prefrontal cortex control verbal semantic organization. C1 Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Savage, CR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, 149-9102,Bldg 149,13th St, Charlestown, MA 02129 USA. EM savage@psych.mgh.harvard.edu RI Heckers, Stephan/F-3051-2010; OI Heckers, Stephan/0000-0003-3601-9910; Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [MH01230, MH50275] NR 63 TC 124 Z9 125 U1 4 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 2001 VL 124 BP 219 EP 231 DI 10.1093/brain/124.1.219 PN 1 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 396CZ UT WOS:000166619900019 PM 11133799 ER PT J AU Reiner, A Stern, EA Wilson, CJ AF Reiner, A Stern, EA Wilson, CJ TI Physiology and morphology of intratelencephalically projecting corticostriatal-type neurons in pigeons as revealed by intracellular recording and cell filling SO BRAIN BEHAVIOR AND EVOLUTION LA English DT Article DE birds; pigeons; telencephalon; basal ganglia; striatum; cortex; evolution ID DORSAL VENTRICULAR RIDGE; LIZARD GEKKO-GECKO; CORTICOTHALAMIC FIBERS; EFFERENT CONNECTIONS; BASAL GANGLIA; COLUMBA-LIVIA; ELECTROPHYSIOLOGICAL CHARACTERISTICS; AMYGDALOID PROJECTIONS; BASOLATERAL AMYGDALA; CLADISTIC-ANALYSIS AB Much of the Wulst and dorsal ventricular ridge (DVR) in birds, which together make up the part of the avian telencephalon functionally resembling mammalian cerebral cortex, projects to the striatum. Those connections arise from neurons projecting additionally to the brain-stem as well as from neurons projecting only within the telencephalon. As part of an effort to further characterize corticostriatal-type projection neurons in birds, we recorded intracellularly from neurons of the outer DVR, identified neurons projecting to the striatum by antidromic stimulation from the ipsilateral rostromedial striatum or subsequently by their axonal projection, characterized these neurons physiologically and then filled them with biocytin. As neurons in the outer DVR only project within telencephalon, neurons within it projecting to the striatum are of the intratelencephalically projecting (IT) type. Our studies suggest that: (1) the membrane potentials of avian IT-type neurons fluctuate between two preferred subthreshold values, and action potentials occur only in the 'up' state, (2) avian IT-type neurons show a time-dependent inward rectification in response to hyperpolarization and regular firing in response to constant current injection, (3) the conduction velocity of avian IT-type neurons is slow (about 0.2 m/s), (4) avian IT-type neurons possess radially disposed densely spiny dendrites but no apical dendrite, (5) avian IT-type neurons have local and distant collateral projections within the DVR, and (6) individual avian IT-type neurons give rise to an extensive terminal field within the striatum. Aside from the shape of their dendritic tree, IT-type neurons in birds closely resemble IT-type corticostriatal neurons in mammals in these various aspects, although it is presently uncertain whether this neuron type has been inherited in common by birds and mammals from stem amniotes. Copyright (C) 2002 S. Karger AG, Basel. C1 Univ Tennessee, Dept Anat & Neurobiol, Memphis, TN 38163 USA. Massachusetts Gen Hosp East, Dept Neurol, Charlestown, MA USA. Univ Texas, Div Life Sci, San Antonio, TX 78285 USA. RP Reiner, A (reprint author), Univ Tennessee, Dept Anat & Neurobiol, 855 Monroe Ave, Memphis, TN 38163 USA. RI Wilson, Charles/D-2529-2011 OI Wilson, Charles/0000-0002-9004-2145 FU NINDS NIH HHS [NS-19620, R01 NS019620, NS-20743] NR 65 TC 16 Z9 16 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0006-8977 J9 BRAIN BEHAV EVOLUT JI Brain Behav. Evol. PY 2001 VL 58 IS 2 BP 101 EP 114 DI 10.1159/000047264 PG 14 WC Behavioral Sciences; Neurosciences; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Zoology GA 517CX UT WOS:000173594500003 PM 11805376 ER PT J AU Basilion, JP AF Basilion, JP TI Current and future technologies for breast cancer imaging SO BREAST CANCER RESEARCH LA English DT Review ID TRANSFERRIN RECEPTOR; IN-VIVO; GENE-EXPRESSION; MAMMOGRAMS; CARCINOMA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NFCR Ctr Mol Anal & Imaging,Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Basilion, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NFCR Ctr Mol Anal & Imaging,Ctr Mol Imaging Res, Bldg 149,13th St 5406, Charlestown, MA 02129 USA. NR 16 TC 5 Z9 6 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2001 VL 3 IS 1 BP 14 EP 16 DI 10.1186/bcr264 PG 3 WC Oncology SC Oncology GA 408TT UT WOS:000167344300005 PM 11300100 ER PT J AU Ntziachristos, V Chance, B AF Ntziachristos, V Chance, B TI Probing physiology and molecular function using optical imaging: applications to breast cancer SO BREAST CANCER RESEARCH LA English DT Review DE contrast agents; diffuse optical tomography; spectral imaging ID IN-VIVO CHARACTERIZATION; CONTRAST AGENTS; TUMORS; SPECTROSCOPY; MAMMOGRAPHY; TOMOGRAPHY; LIGHT; EXPRESSION; EXPERIENCE AB The present review addresses the capacity of optical imaging to resolve functional and molecular characteristics of breast cancer. We focus on recent developments in optical imaging that allow three-dimensional reconstruction of optical signatures in the human breast using diffuse optical tomography (DOT). These technologic advances allow the noninvasive, in vivo imaging and quantification of oxygenated and deoxygenated hemoglobin and of contrast agents that target the physiologic and molecular functions of tumors. Hence, malignancy differentiation can be based on a novel set of functional features that are complementary to current radiologic imaging methods. These features could enhance diagnostic accuracy, lower the current state-of-the-art detection limits, and play a vital role in therapeutic strategy and monitoring. C1 Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Univ Penn, Dept Biochem Biophys, Philadelphia, PA 19104 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St 5406, Charlestown, MA 02129 USA. NR 29 TC 182 Z9 184 U1 1 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2001 VL 3 IS 1 BP 41 EP 46 DI 10.1186/bcr269 PG 6 WC Oncology SC Oncology GA 408TT UT WOS:000167344300010 PM 11250744 ER PT J AU Theodoulou, M Campos, S Welles, L Almonte, A Batist, G Winer, E Hudis, C AF Theodoulou, M Campos, S Welles, L Almonte, A Batist, G Winer, E Hudis, C TI Cardiac safety and efficacy of TLC D99 (D, Myocet (TM)) and Herceptin (R) (H) in advanced breast cancer (ABC). SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Adult Oncol Dept, Boston, MA 02115 USA. Elan Pharmaceut, Princeton, NJ USA. McGill Univ, Jewish Gen Hosp, Dept Oncol, Montreal, PQ H3T 1E2, Canada. NR 0 TC 2 Z9 2 U1 2 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 427 BP 283 EP 283 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800297 ER PT J AU Burstein, HJ Nunes, RA Lester, S Kaelin, CM Harris, LN Winer, EP AF Burstein, HJ Nunes, RA Lester, S Kaelin, CM Harris, LN Winer, EP TI Preoperative trastuzumab (T) and paclitaxel (P) for HER2 overexpressing (HER2+) stage II/III breast cancer: clinical, pathological and serological findings. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Dana Farber Partners Canc Care, Dept Med, Boston, MA USA. Dana Farber Partners Canc Care, Dept Surg, Boston, MA USA. Dana Farber Partners Canc Care, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 507 BP 298 EP 298 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800356 ER PT J AU Burstein, HJ Demetri, GD Shilo, N Mueller, E Spiegelman, B Winer, EP AF Burstein, HJ Demetri, GD Shilo, N Mueller, E Spiegelman, B Winer, EP TI Phase II study of the PPAR gamma-activating ligand troglitazone in treatment-refractory metastatic breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 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 KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 531 BP 304 EP 304 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800380 ER PT J AU Partridge, AH Burstein, HJ Bluman, LG Bunnell, CA Winer, EP AF Partridge, AH Burstein, HJ Bluman, LG Bunnell, CA Winer, EP TI Preferences and attitudes of patients with metastatic breast cancer regarding receiving results information following participation in a clinical trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 543 BP 307 EP 307 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800392 ER PT J AU Chakravarty, G Settleman, J Quan, HK Rosen, JM AF Chakravarty, G Settleman, J Quan, HK Rosen, JM TI p190-B, an unconventional RhoGTPase activating protein, in cell invasion during ductal morphogenesis and mammary tumorignesis. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Harvard Univ, Sch Med, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 565 BP 313 EP 313 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800414 ER PT J AU Cahill, M Karabatzaki, M Donoghue, C Meleady, R Mynett-Johnson, LA Mooney, D Graham, IM Whitehead, AS Shields, DC AF Cahill, M Karabatzaki, M Donoghue, C Meleady, R Mynett-Johnson, LA Mooney, D Graham, IM Whitehead, AS Shields, DC TI Thermolabile MTHFR genotype and retinal vascular occlusive disease SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; CORONARY-ARTERY DISEASE; METHYLENE TETRAHYDROFOLATE REDUCTASE; COMMON MUTATION; RISK FACTOR; VEIN OCCLUSION; MYOCARDIAL-INFARCTION; PLASMA HOMOCYSTEINE; VARIANT; HYPERHOMOCYSTEINEMIA AB Background-Raised levels of total plasma homocysteine (tHcy) are associated with an increased risk of retinal vascular occlusive disease. A thermolabile form of a pivotal enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase (MTHFR), has been associated with vascular occlusive disease and raised tHcy levels. The relation between thermolabile MTHFR genotype, tHcy, and retinal vascular occlusive disease has not been determined. Methods-A retrospective case-control study involving hospital based controls and cases with retinal vascular occlusions in whom tHcy levels had been determined was undertaken. Genotyping for the MTHFR 677 C-T mutation that specifies the thermolabile form of the enzyme was performed by established methods in all subjects. The relation between homozygosity for thermolabile MTHFR genotype (TT), raised tHcy levels, and risk of retinal vascular occlusive disease was examined. Results-87 cases of retinal vascular occlusive disease (mean age 68.7 years) comprising 26 cases of retinal artery occlusion and 61 of retinal vein occlusion were compared with 87 controls (mean age 70.2 years). The TT genotype did not confer a significantly increased risk of retinal vascular occlusive disease. The mean tHcy level was significantly higher in the cases than in the controls (p<0.0001). Overall, and in both the cases and controls, the frequency of the TT genotype was higher in those with normal tHcy levels than in those with increased levels of tHcy. However, the TT genotype did not significantly alter the risk of increased tHcy levels in these patients. Conclusions-The TT genotype is not associated with an increased risk of retinal vascular occlusive disease or increased tHcy levels in this group of elderly patients. In older patients, nutritional rather than genetic factors may be more important in increasing tHcy levels, a known risk factor for retinal vascular occlusive disease. C1 Royal Victoria Eye & Ear Hosp, Res Fdn, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Genet, Dublin 2, Ireland. Natl Childrens Hosp, Adelaide Meath Hosp, Dept Cardiol, Dublin 24, Ireland. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Pharmacogenet, Philadelphia, PA 19104 USA. Royal Coll Surg Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. RP Cahill, M (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. NR 32 TC 24 Z9 25 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JAN PY 2001 VL 85 IS 1 BP 88 EP 90 DI 10.1136/bjo.85.1.88 PG 3 WC Ophthalmology SC Ophthalmology GA 390ZA UT WOS:000166328600020 PM 11133719 ER PT J AU Yang, YK Ke, QG Cai, JB Xiao, YF Morgan, JP AF Yang, YK Ke, QG Cai, JB Xiao, YF Morgan, JP TI Evidence for cocaine and methylecgonidine stimulation of M-2 muscarinic receptors in cultured human embryonic lung cells SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; methylecgonidine; carbachol; cyclic AMP; cyclic GMP; muscarinic receptor ID ACUTE MYOCARDIAL-INFARCTION; ADENYLATE-CYCLASE ACTIVITY; NITRIC-OXIDE; CHOLINERGIC RECEPTORS; VENTRICULAR MYOCYTES; CARDIAC MYOCYTES; ACETYLCHOLINE; HEART; FERRET; ABUSE AB 1 Muscarinic cholinoceptor stimulation leads to an increase in guanylyl cyclase activity and to a decrease in adenylyl cyclase activity. This study examined the effects of cocaine and methylecgonidine (MEG) on muscarinic receptors by measurement of cyclic GMP and cyclic AMP content in cultured human embryonic lung (HEL299) cells which specifically express M-2 muscarinic receptors. 2 A concentration-dependent increase in cyclic GMP production was observed in HEL299 cells incubated with carbachol, cocaine, or MEG for 24 h. The increase in cyclic GMP content was 3.6 fold for 1 muM carbachol (P < 0.01), 3.1 fold for 1 M cocaine (P < 0.01), and 7.8 fold for 1 M MEG (P < 0.001), respectively. This increase in cyclic GMP content was significantly attenuated or abolished by the muscarinic receptor antagonist atropine or the MZ blocker methoctramine. 3 In contrast, cocaine, MEG, and carbachol produced a significant inhibition of cyclic AMP production in HEL299 cells. Compared to the control, HEL299 cells treated with 1 M cocaine decreased cyclic AMP production by 30%. MEG and carbachol at 1 muM decreased cyclic AMP production by 37 and 38%, respectively. Atropine or methoctramine at 1 or 10 muM significantly attenuated or abolished the cocaine-induced decrease in cyclic AMP production. However, the antagonists alone had neither an effect on cyclic GMP nor cyclic AMP production. Pretreatment of HEL299 cells with pertussis toxin prevented the cocaine-induced reduction of cyclic AMP production. 4 Western blot analysis showed that HEL299 cells specifically express M-2 muscarinic receptors without detectable M-1 and M-3. Incubation of HEL299 cells with cocaine, carbachol, and atropine did not alter the expression of M-2 protein levels. However, the inducible isoform of nitric oxide synthase (iNOS) was induced in the presence of cocaine or carbachol and this induction was significantly attenuated after addition of atropine or methoctramine. 5 The present data show that cocaine and MEG significantly affect cyclic GMP and cyclic AMP production in cultured HEL299 cells. Our results also show that these effects result from the drug-induced stimulation of M-2 muscarinic receptors accompanied with no alterations of receptor expression. However, the induction of iNOS by cocaine may result in the increase in cyclic GMP production. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc,Harvard Thorndike Lab,Dept Med, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Charles A Dana Res Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02215 USA. RP Morgan, JP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc,Harvard Thorndike Lab,Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. FU NIDA NIH HHS [DA11762, DA12774] NR 45 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2001 VL 132 IS 2 BP 451 EP 460 DI 10.1038/sj.bjp.0703819 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 398BU UT WOS:000166736500010 PM 11159694 ER PT J AU Goulder, PJR Jeena, P Tudor-Williams, G Burchett, S AF Goulder, PJR Jeena, P Tudor-Williams, G Burchett, S TI Paediatric HIV infection: correlates of protective immunity and global perspectives in prevention and management SO BRITISH MEDICAL BULLETIN LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; RURAL SOUTH-AFRICA; TYPE-1 INFECTION; HETEROSEXUAL TRANSMISSION; DISEASE PROGRESSION; CHILD TRANSMISSION; ESCAPE VARIANTS; PLASMA VIREMIA; HOMOSEXUAL MEN AB The impact of the HIV epidemic on child health globally is beginning to be appreciated. With the burden of new infections falling on young women, there is a skyrocketing number of AIDS orphans, and a rapidly increasing number of children infected via mother-to-child-transmission (MTCT). An estimated 600,000 new paediatric infections occur each year, of which some 1500/day (>90%) occur in sub-Saharan Africa. But whereas children account for only 4% of those currently living with HIV infection, 20% of AIDS deaths have been in children. This reflects the rapid progression to disease in paediatric HIV infection. Whereas a dramatic reduction in viraemia follows acute adult infection, corresponding to the appearance of a vigorous anti-HIV cytotoxic T lymphocyte response, virtually no impact of the immune response is observed in acute paediatric infection following MTC-T. Two specific challenges for the paediatric immune response are: (i) infection occurs before the immune system itself is fully developed; and (ii) the viruses transmitted by MTCT have already evaded an immune system sharing close genetic relatedness to that of the child. Accumulating evidence! indicates that the immune system is potentially capable of effective control of HIV infection, and that events occurring in acute infection critically determine the ultimate outcome. Technological advances that have transformed the study of T-cell immunity now enable the developing immune system in childhood to be better understood. Via novel immunotherapeutic approaches described, it may be possible to modulate the infant's immune response to reach effective and durable suppression of HIV, as can be achieved by the rare long-term non-progressors of HIV infection. The feasibility of adopting these approaches globally are as yet untested. Finally, the striking disparity between the burden of paediatric HIV infection and access to the necessary infrastructure and therapeutic options required for its optimal management is addressed in a comparison between three sites of paediatric HIV care: Durban, South Africa; London, UK; and Boston, USA. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Dept Paediat, Oxford OX3 9DU, England. Univ Natal, King Edward VIII Hosp, Dept Paediat, Durban, South Africa. Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Dept Paediat, London, England. Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Goulder, PJR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 13th St,Bldg 149,Rm 5219, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI46995] NR 81 TC 26 Z9 26 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-1420 J9 BRIT MED BULL JI Br. Med. Bull. PY 2001 VL 58 BP 89 EP 108 DI 10.1093/bmb/58.1.89 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 493AG UT WOS:000172199400008 PM 11714626 ER PT J AU Clyman, B AF Clyman, B TI Sports, exercise, and arthritis SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Article ID OSTEOARTHRITIS; KNEE; HIP; JOINT; RISK; DISEASE; PLAYERS C1 Greater Los Angeles VA Med Syst, Dept Ambulatory Care, Los Angeles, CA USA. RP Clyman, B (reprint author), Greater Los Angeles VA Med Syst, Dept Ambulatory Care, Los Angeles, CA USA. NR 22 TC 3 Z9 3 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1330 W PEACH TREE ST, ATLANTA, GA 30309 USA SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PY 2001 VL 50 IS 6 BP 1 EP 3 PG 5 WC Rheumatology SC Rheumatology GA 447UE UT WOS:000169590200001 PM 11450272 ER PT J AU Helfgott, SM AF Helfgott, SM TI Sensible approach to low back pain SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Article ID FREQUENCY; US C1 Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Helfgott, SM (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 USA SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PY 2001 VL 50 IS 3 BP 1 EP 4 PG 6 WC Rheumatology SC Rheumatology GA 428FZ UT WOS:000168452200001 PM 12386944 ER PT J AU Jacobson, AF Shapiro, CL Van den Abbeele, AD Kaplan, WD AF Jacobson, AF Shapiro, CL Van den Abbeele, AD Kaplan, WD TI Prognostic significance of the number of bone scan abnormalities at the time of initial bone metastatic recurrence in breast carcinoma SO CANCER LA English DT Article DE breast carcinoma; radionuclide imaging; metastasis; bone ID FOLLOW-UP; CANCER PATIENTS; SKELETAL SCINTIGRAPHY; ADJUVANT CHEMOTHERAPY; RANDOMIZED TRIAL; STAGE-I; DIAGNOSIS; THERAPY AB BACKGROUND. To gain insight into the factors that contribute to the more favorable prognosis associated with recurrence limited to bone in patients with breast carcinoma, the authors analyzed the number of sites of initial involvement identified on radionuclide bone scans in relation to long term outcome. METHODS. Records of 641 patients with clinical Stage I-III breast carcinoma that originally was diagnosed in 1974-1985 were reviewed. During follow-up, 295 patients (46%) experienced distant recurrence, including 116 with bone as the sole initial site of metastatic disease. Radionuclide bone scans identified the initial site(s) of recurrence in 113 of these latter 116 patients, and these studies were categorized by the number of skeletal lesions subsequently confirmed as metastases (1, 2, or greater than or equal to 3). Survival from time of recurrence and time of original diagnosis was analyzed using Kaplan-Meier methods, and factors associated with recurrence and mortality were examined using logistic and Cox regression. RESULTS. Median survival from time of recurrence was 35 months in the patients with bone-only metastases, compared with 11-26 months for all other sites of visceral recurrence exclusive of bone. Number of positive lymph nodes and estrogen receptor status were the only predictive variables for recurrence. Median survival from time of recurrence and time of original diagnosis for the 3 bone scan categories was: 1 lesion (n = 47), 53 and 86 months; 2 lesions (n = 22), 38 and 68 months; and > 3 lesions (n = 44), 22 and 58 months (P < 0.0001 and P < 0.005 for 1 and 2 lesions vs greater than or equal to 3). In the "bone-only" group, the number of scan lesions was the strongest predictor of length of survival. CONCLUSIONS. Patients with breast carcinoma who experience a recurrence in bone at only one or two sites initially have a survival advantage over those with more extensive (greater than or equal to 3 sites) skeletal metastases and those with metastatic disease involving other visceral organs. C1 Vet Affairs Puget Sound Hlth Care Syst, Nucl Med Sect, Seattle, WA 98108 USA. Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Nucl Med, Boston, MA 02115 USA. RP Jacobson, AF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Nucl Med Sect, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 46 TC 23 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2001 VL 91 IS 1 BP 17 EP 24 DI 10.1002/1097-0142(20010101)91:1<17::AID-CNCR3>3.0.CO;2-K PG 8 WC Oncology SC Oncology GA 432DD UT WOS:000168675200003 PM 11148555 ER PT J AU Barbeau, EM AF Barbeau, EM TI Addressing class-based disparities related to tobacco: working with labor unions SO CANCER CAUSES & CONTROL LA English DT Article ID CIGARETTE-SMOKING; CANCER C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Cambridge, MA 02138 USA. RP Barbeau, EM (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. NR 8 TC 10 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2001 VL 12 IS 1 BP 91 EP 93 DI 10.1023/A:1008933730862 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 393EE UT WOS:000166455600010 PM 11227929 ER PT J AU Ferguson, WS Goorin, AM AF Ferguson, WS Goorin, AM TI Current treatment of osteosarcoma SO CANCER INVESTIGATION LA English DT Review ID HIGH-DOSE METHOTREXATE; LIPOSOMAL MURAMYL TRIPEPTIDE; WHOLE-LUNG IRRADIATION; PRIMARY OSTEOGENIC-SARCOMA; PEDIATRIC-ONCOLOGY-GROUP; HIGH-GRADE OSTEOSARCOMA; POSTOPERATIVE ADJUVANT CHEMOTHERAPY; SURGERY NEOADJUVANT CHEMOTHERAPY; MALIGNANT FIBROUS HISTIOCYTOMA; HISTOLOGIC TUMOR RESPONSE C1 Rhode Isl Hosp, Div Pediat Hematol Oncol, Providence, RI 02903 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ferguson, WS (reprint author), Rhode Isl Hosp, Div Pediat Hematol Oncol, 593 Eddy St, Providence, RI 02903 USA. NR 308 TC 179 Z9 201 U1 1 U2 11 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2001 VL 19 IS 3 BP 292 EP 315 DI 10.1081/CNV-100102557 PG 24 WC Oncology SC Oncology GA 453ME UT WOS:000169919000010 PM 11338887 ER PT J AU Lester, EP Petroni, GR Barcos, M Johnson, JL Millard, FE Cooper, MR Omura, GA Frei, E Peterson, BA AF Lester, EP Petroni, GR Barcos, M Johnson, JL Millard, FE Cooper, MR Omura, GA Frei, E Peterson, BA TI Cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) for advanced-stage Hodgkin's disease: CALGB 8856 SO CANCER INVESTIGATION LA English DT Article DE advanced stage; chemotherapy; cyclophosphamide; doxorubicin; etoposide; Hodgkin's disease; prednisone; vincristine ID BONE-MARROW TRANSPLANTATION; COMBINATION CHEMOTHERAPY; CLINICAL-TRIALS; HYBRID REGIMEN; DOSE INTENSITY; MOPP; THERAPY; LYMPHOMA; LEUKEMIA; ABVD AB Successful treatment of advanced-stage Hodgkin's disease (HD) may critically depend on dose intensity. Because mechlorethamine, Oncovin, procarbazine, and prednisone (MOPP), aid Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) are not suitable for major dose escalation, we evaluated the activity and toxicity of combined cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) in advanced HD, here used at conventional dose intensity, as a preparatory study prior to using this regimen at higher dose intensity. Ninety-two patients were treated with CHOPE (cyclophosphamide, 750mg/m(2), day 1; doxrudicin, 50mg/m(2), day 1; vincristine, 1.4mg/m(2), day 1 and 8; prednisone, 100 mg/day, days 1-5; and etoposide, 80 mg/m(2), days 1, 2, and 3) every 21 days. All had advanced HD with no prior chemotherapy with 46% stage IV, 63% with B symptoms, and 57% with bulky disease (>5 cm). Radiation and growth factor support were not permitted. Full-dose vincristine (not capped at maximum 2 mg/dose) was used in the first 33 patients. An initial cohort of 41 patients was treated with four cycles of CHOPE to evaluate safety and efficacy followed by four cycles of ABVD. A second cohort of 51 patients was treated with 6-8 cycles of CHOPE alone. Toxicity was generally acceptable and primarily hematologic, with neutrophils < 500 in 63% of cohort I and 90% of cohort II, and platelets < 25,000 in 7% of cohort I and 8% of cohort II. The long-term neurotoxicity of full-dose, high-intensity vincristine was acceptable and largely reversible. In cohort I, 92% of patients achieved a complete response (CR) or partial response (PR) with four cycles of CHOPE and 85% were in CR after four additional cycles of ABVD. In cohort II, 77% achieved a CR with 6-8 cycles of CHOPE alone. FFS was 76% in cohort I and 59% in cohort II, with a median follow-up of 8.2 and 5.7 years, respectively. CHOPE, at conventional close intensity as used here, is an effective first-line regimen for the treatment advanced-stage HD and may warrant evaluation using higher closes of cyclophosphamide and etopaside with granulocyte colony stimulating factor (G-CSF) support. C1 Lakeland Med Ctr, St Joseph, MI USA. CALGB Biostat Ctr, Durham, NC USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. USN, Med Ctr, San Diego, CA 92152 USA. Wake Forest Univ, Bowman Gray Sch Med, Ctr Comprehens Canc, Winston Salem, NC USA. Univ Alabama, Birmingham, AL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Minneapolis, MN USA. RP Lester, EP (reprint author), Oncol Care Associates, 820 Lester Ave, St Joseph, MI 49085 USA. FU NCI NIH HHS [CA16450, CA32291, CA31946, CA03927, CA02599, CA47545, CA47555, CA33601, CA11789] NR 41 TC 3 Z9 3 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2001 VL 19 IS 5 BP 447 EP 458 DI 10.1081/CNV-100103843 PG 12 WC Oncology SC Oncology GA 453MG UT WOS:000169919200001 PM 11458812 ER PT J AU Bennett, CL Hynes, D Godwin, J Stinson, TJ Golub, RM Appelbaum, FR AF Bennett, CL Hynes, D Godwin, J Stinson, TJ Golub, RM Appelbaum, FR TI Economic analysis of granulocyte colony stimulating factor as adjunct therapy for older patients with acute myelogenous leukemia (AML): Estimates from a Southwest Oncology Group clinical trial SO CANCER INVESTIGATION LA English DT Article DE costs; cost effectiveness; filgrastim; leukemia ID ACUTE MYELOID-LEUKEMIA; ADULT PATIENTS GREATER-THAN-55; CONTROLLED PHASE-III; ELDERLY PATIENTS; INDUCTION TREATMENT; COOPERATIVE GROUP; DOUBLE-BLIND; CHEMOTHERAPY; FILGRASTIM; AGE AB Considerable morbidity, mortality, and economic costs result during remission induction therapy for elderly patients with acute myeloid leukemia (AML). in this study, the economic costs of adjunct granulocyte colony stimulating factor (G-CSF) are estimated for AML patients > 55 years of age who received induction chemotherapy on a recently completed Southwest Oncology Group study (SWOG). Clinical data were based on Phase III trial information from 207 AML patients who were randomized to receive either placebo or G-CSF post-induction therapy. Analyses were conducted using a decision analytic model with the primary source of clinical event probabilities based on in-hospital care with or without all active infection requiring intravenous antibiotics. Estimates of average daily costs of care with and without an infection were impoted from a previously reported economic model of a similar population. When compared to AML patients who received placebo, patients who received G-CSF had significantly fewer days on intravenous antibiotics (median 22 vs. 26, p = 0.05), whereas overall duration of hospitalzation did not differ (median 29 days). The median cost per day with all active infection that required intravenous antibiotics was estimated to be $1742, whereas the median cost per day without an active infection was estimated to De $1467. Overall costs were $49, 693 for the placebo group and $50,593 for the G-CSF patients. G-CSF during induction chemotherapy for elderly patients with AML had some clinical benefits, but it did not reduce the duration of hospitalization, prolong survival, or reduce the overall cost of supportive care. Whether the benefits of G-CSF therapy justify its use in individual patients with acute leukemia for the present remains a matter of clinical judgement. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, VA Informat Resource Ctr, Hines, IL 60141 USA. Loyola Univ, Dept Med, Maywood, IL 60153 USA. Loyola Univ, Dept Hematol Oncol, Maywood, IL 60153 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Northwestern Univ, Dept Med, Div Gen Internal Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. VA Chicago Hlth Care Syst Lakeside, Chicago, IL USA. RP Bennett, CL (reprint author), VAMC Mat Sci Bldg 400E,Suite 205, Chicago, IL 60611 USA. RI Bennett, Charles/C-2050-2008 FU NCI NIH HHS [CA-32102, CA-38926] NR 21 TC 26 Z9 27 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2001 VL 19 IS 6 BP 603 EP 610 DI 10.1081/CNV-100104288 PG 8 WC Oncology SC Oncology GA 454LT UT WOS:000169974600005 PM 11486703 ER PT J AU Cooley, ME Kaiser, LR Abrahm, JL Giarelli, E AF Cooley, ME Kaiser, LR Abrahm, JL Giarelli, E TI The silent epidemic: Tobacco and the evolution of lung cancer and its treatment SO CANCER INVESTIGATION LA English DT Review DE lung cancer and quality of life; lung cancer treatment; tobacco control ID QUALITY-OF-LIFE; SUPPORTIVE CARE; UNITED-STATES; CLINICAL OUTCOMES; PLUS CHEMOTHERAPY; BONE METASTASES; HUMAN COSTS; TRIAL; SMOKING; PAIN AB Considered a rare disease during the 19th century lung cancer became the most virulent and lethal cause of cancer mortality by the end of the 20th century. In this paper, lung cancer and its treatment are addressed within the social, cultural, economic, and political context of the last century. Because lung cancer is related to the consumption of cigarettes, the battles over tobacco control are highlighted. Four time periods are addressed: the early years (1900-1930), beginning of the epidemic (1930-1960), defining the problem (1960-1980), and expanding options (1980-1990s). Although improvements have been made in science and technology, attempts at finding curative treatments have met with little success. Smoking cessation and efforts to control tobacco (especially, among children and adolescents) remain the most important factors if the incidence of lung cancer is to be curtailed in the future. Providing care to individuals with the illness is a current challenge. Research examining the efficacy, of treatments and their effect on survival, health-related quality of life, and cost outcomes is essential and can be best achieved through the efforts of multidisciplinary teams. C1 Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Hosp Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Harvard Sch Dent Med, Smoking Cessat Res Program, Boston, MA USA. RP Cooley, ME (reprint author), 8 Marlborough St, Boston, MA 02116 USA. FU NINR NIH HHS [T32NR07035] NR 116 TC 5 Z9 6 U1 2 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2001 VL 19 IS 7 BP 739 EP 751 DI 10.1081/CNV-100106149 PG 13 WC Oncology SC Oncology GA 474GY UT WOS:000171099000009 PM 11577815 ER PT J AU Kozin, SV Boucher, Y Hicklin, DJ Bohlen, P Jain, RK Suit, HD AF Kozin, SV Boucher, Y Hicklin, DJ Bohlen, P Jain, RK Suit, HD TI Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts SO CANCER RESEARCH LA English DT Article ID IONIZING-RADIATION; MAMMARY-CARCINOMA; ANGIOGENESIS; THERAPY; TNP-470; CELLS; MICE AB Antiangiogenic therapy can enhance radiation-induced tumor growth inhibition. However, the effects of combined antiangiogenic and radiation therapy on long-term tumor control and normal tissue response have not been reported. We treated mice bearing two different human tumor xenografts with anti-vascular endothelial growth factor receptor-2 antibody (DC101) and five dose fractions of local radiation and followed them for at least 6 months. DC101 significantly decreased the dose of radiation necessary to control 50% of tumors locally. The decrease was 1.7- and 1.3-fold for the moderately radiosensitive small cell lung carcinoma 54A and the highly radioresistant glioblastoma multiforme U87, respectively. In contrast to tumors, no increase in skin radiation reaction by the antibody was detected. Surprisingly, 44% of mice bearing 54A tumor developed clear ascites after DC101 treatment at its highest dose; this was fatal to 20% of mice. This adverse effect was seen only in mice that received whole-body irradiation 1 day before tumor implantation. The encouraging results on two human tumor xenografts suggest that vascular endothelial growth factor receptor-2 blockade merits further investigation to assess its potential as an enhancer of radiation therapy in the clinic. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. ImClone Syst Inc, Dept Immunol, New York, NY 10014 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [R35-CA-56591, R37-CA-13111, T32-CA-73479] NR 24 TC 232 Z9 245 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2001 VL 61 IS 1 BP 39 EP 44 PG 6 WC Oncology SC Oncology GA 392WR UT WOS:000166436000010 PM 11196192 ER PT J AU Teshima, T Mach, N Hill, GR Pan, LY Gillessen, S Dranoff, G Ferrara, JLM AF Teshima, T Mach, N Hill, GR Pan, LY Gillessen, S Dranoff, G Ferrara, JLM TI Tumor cell vaccine elicits potent antitumor immunity after allogeneic T-cell-depleted bone marrow transplantation SO CANCER RESEARCH LA English DT Article ID VERSUS-HOST-DISEASE; GENE-TRANSFER; CHRONIC GRAFT; IMMUNIZATION; LEUKEMIA; DONOR; RECONSTITUTION; RECIPIENTS; IMMUNOTHERAPY; MICE AB Allogeneic bone marrow transplantation (BMT) is currently restricted to hematological malignancies because of a lack of antitumor activity against solid cancers. We have tested a novel treatment strategy to stimulate specific antitumor activity against a solid tumor after BMT by vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). Using the B16 melanoma model, we found that vaccination elicited potent antitumor activity in recipients of syngeneic BMT in a time-dependent fashion, and that immune reconstitution was critical for the development of antitumor activity. Vaccination did not stimulate antitumor immunity after allogeneic BMT because of the post-BMT immunodeficiency associated with graft-versus-host disease (GVHD). Remarkably, vaccination was effective in stimulating potent and long-tasting antitumor activity in recipients of T-cell-depleted (TCD) allogeneic bone marrow. Recipients of TCD bone marrow who showed significant immune reconstitution by 6 weeks after BMT developed B16-specific T-cell-cytotoxic, proliferative, and cytokine responses as a function of vaccination. T cells derived from donor stem cells were, therefore, able to recognize tumor antigens, although they remained tolerant to host histocompatibility antigens. These results demonstrate that GM-CSF-based tumor cell vaccines after allogeneic TCD BMT can stimulate potent antitumor effects without the induction of GVHD, and this strategy has important implications for the treatment of patients with solid malignancies. C1 Univ Michigan, Ctr Canc, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Dept Pediat, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ferrara, JLM (reprint author), Univ Michigan, Ctr Canc, Dept Internal Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI teshima, takanori/G-1671-2012; Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 FU NCI NIH HHS [CA74886, CA39542]; NHLBI NIH HHS [HL55162] NR 52 TC 70 Z9 74 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2001 VL 61 IS 1 BP 162 EP 171 PG 10 WC Oncology SC Oncology GA 392WR UT WOS:000166436000029 PM 11196155 ER PT J AU Wang, HC Zeng, ZC Bui, TA DiBiase, SJ Qin, W Xia, F Powell, SN Iliakis, G AF Wang, HC Zeng, ZC Bui, TA DiBiase, SJ Qin, W Xia, F Powell, SN Iliakis, G TI Nonhomologous end-joining of ionizing radiation-induced DNA double-stranded breaks in human tumor cells deficient in BRCA1 or BRCA2 SO CANCER RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASE; SUSCEPTIBILITY GENE BRCA2; CANCER-CELLS; GEL-ELECTROPHORESIS; EUKARYOTIC CELLS; DAMAGE RESPONSE; MAMMALIAN-CELLS; MEIOTIC CELLS; CHO CELLS; REPAIR AB Mutations in the BRCA1 or BRCA2 genes predispose to a wide spectrum of familial cancers. The functions of the proteins encoded by BRCA1 and BRCA2 remain to be elucidated, but their interaction and colocalization with hRAD51 suggest a role in homologous recombination and DNA double-strand break (DSB) repair. The role of BRCA1 and BRCA2 in the rejoining of ionizing radiation (IR)-induced DNA DSBs, which may represent a step in the overall process of repair, remains uncertain because recent reports provide conflicting results. Because elucidation of the role of these proteins in DNA DSB rejoining is important for their functional characterization, we reexamined this end point in cells with mutations in either BRCA1 or BRCA2. We show that two pancreatic carcinoma cell lines known to have either wild-type (BxPC3) or mutant forms (Capan-1) of BRCA2 rejoin IR-induced DNA DSBs to a similar extent following biphasic kinetics characterized by a fast and a slow component. Importantly, inactivation of DNA-dependent protein kinase (DNA-PK) by wortmannin generates similar shifts from the fast to the slow component of rejoining in BRCA2-proficient and BRCA2-deficient cells. This suggests that the functioning of either the fast, DNA-PK-dependent component or the slow, DNA-PK-independent component of rejoining Is not affected by mutations in BRCA2. Also, a human breast cancer cell line with mutated BRCA1 shows normal rejoining of IR-induced DNA DSBs and levels of inhibition by wortmannin commensurate with the degree of DNA-PK inhibition. These observations fail to confirm a direct role for BRCA1 or BRCA2 in the rejoining of IR-induced DSBs in the genome of human tumor cells and, as a result, an involvement in nonhomologous end-joining. They are in line with similar observations with mutants deficient in genes implicated in homologous recombination and support the view that the radiosensitivity to killing of cells deficient in BRCA1 or BRCA2 derives from defects in this repair pathway. C1 Jefferson Med Coll, Kimmel Canc Ctr, Dept Radiat Oncol, Div Expt Radiat Oncol, Philadelphia, PA 19107 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Lab Mol & Cellular Radiat Biol, Charlestown, MA 02129 USA. RP Iliakis, G (reprint author), Thomas Jefferson Univ, Dept Radiat Oncol, Thompson Bldg,Room B-1,1020 Sansom St, Philadelphia, PA 19107 USA. RI Xia, Fen/G-3708-2013 FU NCI NIH HHS [P30-CA56036, CA42026] NR 47 TC 103 Z9 106 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2001 VL 61 IS 1 BP 270 EP 277 PG 8 WC Oncology SC Oncology GA 392WR UT WOS:000166436000044 PM 11196174 ER PT J AU Kiesz, RS Rozek, MM Bouknight, D AF Kiesz, RS Rozek, MM Bouknight, D TI Bilateral carotid stenting combined with three-vessel percutaneous coronary intervention in single setting SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE carotid arteries; coronary arteries; stenting ID ARTERY DISEASE; SURGICAL APPROACH; ENDARTERECTOMY; SURGERY AB We describe a patient who underwent bilateral internal carotid artery stenting and three-vessel percutaneous coronary intervention during the same procedure. Stenting of carotid arteries was performed employing our innovative technique combining coronary and peripheral devices. No complications occurred. The patient was discharged home 1 day after the intervention and remains asymptomatic, leading a fully active life. To our knowledge, unstaged bilateral carotid stenting combined with three-vessel coronary intervention has not been reported previously. Cathet Cardiovasc Intervent 2001;52: 100-104. (C) 2001 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie Murphy Div, Cardiac Catheterizat Labs, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, San Antonio, TX 78284 USA. RP Kiesz, RS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 10 TC 9 Z9 9 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 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JAN PY 2001 VL 52 IS 1 BP 100 EP 104 DI 10.1002/1522-726X(200101)52:1<100::AID-CCD1024>3.0.CO;2-A PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 388DU UT WOS:000166162800024 PM 11146534 ER PT J AU Durante, W AF Durante, W TI Regulation of L-arginine transport and metabolism in vascular smooth muscle cells SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Review DE L-arginine; L-ornithine; cationic amino acid transporter; nitric oxide; polyamines; L-proline; inflammatory mediators; growth factors; hemodynamic forces ID NITRIC-OXIDE SYNTHASE; AMINO-ACID TRANSPORTER; NECROSIS-FACTOR-ALPHA; ECOTROPIC RETROVIRUS RECEPTOR; ARTERY ENDOTHELIAL-CELLS; RAT-LIVER ARGINASE; HYDROXY-L-ARGININE; ORAL L-ARGININE; GENE-EXPRESSION; ORNITHINE DECARBOXYLASE AB L-Arginine is a semi-essential amino acid that is metabolized to important regulatory molecules. L-Arginine is transported into vascular smooth muscle cells (SMC) by the cationic amino acid transporter (CAT) family of proteins where it is metabolized to nitric oxide (NO), polyamines, or L-proline. Inflammatory mediators, growth factors, and hemodynamic forces stimulate the transport of L-arginine in vascular SMC by inducing CAT gene expression. However, they exert highly specific and divergent regulatory effects on L-arginine metabolism. Inflammatory cytokines induce the expression of inducible NO synthase (iNOS) and direct the metabolism of L-arginine to the antiproliferative gas, NO. In contrast, growth factors stimulate the expression of arginase I and ornithine decarboxylase (ODC) and channel the metabolism of L-arginine to growth stimulatory polyamines. Alternatively, cyclic mechanical strain blocks both iNOS and ODC activity and stimulates arginase I gene expression, directing the metabolism of L-arginine to the formation of L-proline and collagen. Thus, specific biochemical and biophysical stimuli that are found in the circulation regulate the transport and metabolism of L-arginine in vascular SMC. The ability of these physiologically relevant stimuli to upregulate L-arginine transport and generate specific L-arginine metabolites modulates SMC function and may influence the development of vascular disease. C1 VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. RP Durante, W (reprint author), VA Med Ctr, Bldg 109,Rm 130,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL 59976] NR 126 TC 24 Z9 26 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2001 VL 35 IS 1 BP 19 EP 34 DI 10.1385/CBB:35:1:19 PG 16 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 471EC UT WOS:000170913800002 PM 11898853 ER PT J AU Xie, Y Chen, CM Hume, DA AF Xie, Y Chen, CM Hume, DA TI Transcriptional regulation of c-fms gene expression SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Review ID COLONY-STIMULATING FACTOR; FACTOR-I RECEPTOR; M-CSF RECEPTOR; INDUCED MONOCYTIC DIFFERENTIATION; OSTEOPETROTIC OP/OP MOUSE; CARCINOMA CELL-LINES; MYB MESSENGER-RNA; OP OP MOUSE; NF-KAPPA-B; BONE-MARROW C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Mol & Cellular Biol Lab, Boston, MA 02115 USA. Univ Queensland, Dept Microbiol, Brisbane, Qld 4072, Australia. Univ Queensland, Dept Biochem, Brisbane, Qld 4072, Australia. Univ Queensland, Ctr Cellular & Mol Biol, Brisbane, Qld 4072, Australia. RP Xie, Y (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Hume, David/C-7695-2013 NR 152 TC 16 Z9 16 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2001 VL 34 IS 1 BP 1 EP 16 DI 10.1385/CBB:34:1:001 PG 16 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 435CW UT WOS:000168860700001 PM 11394438 ER PT J AU Kim, K Lee, KY AF Kim, K Lee, KY TI Tyrosine phosphorylation translocates beta-catenin from cell-cell interface to the cytoplasm, but does not significantly enhance the LEF-1-dependent transactivating function SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE beta-catenin; LEF-1; cyclin D1; tyrosine; phosphorylation; kinase; phosphatase ID TRANSCRIPTION FACTOR LEF-1; CYCLIN D1; TARGET; APC; EXPRESSION; ADHESION; COMPLEX; IDENTIFICATION; KINASES; PATHWAY AB beta -catenin plays an essential role in cells, not only as a cadherin-associated complex, but also as a signaling molecule in the nucleus. Tyrosine phosphorylation of beta -catenin has been shown to correlate with tumorigenesis, cell migration, and developmental processes. However, its exact effects on downstream targets in the nucleus are not yet clear. In this study, we used HCT-15 colon carcinoma and NIH 3T3 fibroblasts as models to investigate the effects of a phosphotyrosine phosphatase (PTPase) inhibitor on the localization of beta -catenin, the binding affinity to LEF-1 (Lymphoid Enhancer Factor), and on LEF-1-dependent transactivation function. Treatment with a PTPase inhibitor, pervanadate, increased the tyrosine phosphorylation of beta -catenin in a time-dependent manner and led to its relocation from cell-cell interfaces to the cytoplasm. This phosphorylation/dephosphorylation of beta -catenin does not require its presence at cell-cell interfaces. However, tyrosine phosphorylation of beta -catenin does not change its binding affinity to LEF-1 nor enhance cyclin D1 transactivation, a nuclear target of beta -catenin/LEF-1. This result suggests that tyrosine phosphorylation of beta -catenin has effects on the binding to cadherins in the cytoplasm but not on its LEF-1-dependent transactivating function in the nucleus. (C) 2001 Academic Press. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Lee, KY (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 27 TC 20 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2001 VL 25 IS 5 BP 421 EP 427 DI 10.1006/cbir.2000.0650 PG 7 WC Cell Biology SC Cell Biology GA 438KZ UT WOS:000169053700004 PM 11401329 ER PT J AU Goldmann, WH AF Goldmann, WH TI Phosphorylation of filamin (ABP-280) regulates the binding to the lipid membrane, integrin, and actin SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE tyrosine phosphorylation; filamin (ABP-280); actin; integrin; lipid membrane ID TYROSINE KINASE; PROTEIN; ACTIVATION; FRAGMENTS; INSERT; LEADS; LCK; LYN AB Actin-binding protein (ABP-280: filamin) is a phosphoprotein present in the periphery of the cytoplasm, where it can cross-link actin filaments, associate with lipid membranes, and bind to membrane surface receptors. Given its function and localization in the cell, the hypothesis that it serves as a substrate for p56(lek), a lymphocyte-specific member of the src family of protein tyrosine kinases associated with cell surface glycoproteins is considered. The results suggest conformationally-induced regulation of filamin (ABP-280). (C) 2001 Academic Press. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 23 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2001 VL 25 IS 8 BP 805 EP 808 DI 10.1006/cbir.2000.0710 PG 4 WC Cell Biology SC Cell Biology GA 461UP UT WOS:000170382100011 PM 11482904 ER PT J AU Goldmann, WH Sharma, AL Currier, SJ Johnston, PD Rana, A Sharma, CP AF Goldmann, WH Sharma, AL Currier, SJ Johnston, PD Rana, A Sharma, CP TI Saw Palmetto Berry Extract inhibits cell growth and Cox-2 expression in prostatic cancer cells SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE Saw Palmetto berry extract; cell growth inhibition; MTT and SRB assays; Cox-2; Cox-1; Bcl-2 ID SERENOA-REPENS PERMIXON(R); URINARY-TRACT SYMPTOMS; PC-SPES; ANDROGEN RECEPTOR; LNCAP CELLS; BENIGN; HYPERPLASIA; PROLIFERATION; APOPTOSIS; ANTIGEN AB The cytotoxicity of a commonly used material to alleviate the symptoms of benign prostatic hyperplasia (BPH), Saw Palmetto Berry Extract (SPBE), was examined as neat oil using a set of prostatic cell lines; 267B-1, BRFF-41T and LNCaP. Proliferation of these prostatic derived cell lines is inhibited to different degrees when dosed for 3 days with SPBE. The amount of SPBE required to inhibit 50% growth (IC50) Of these cell lines was 20-30 nl equivalents of SPBE per ml of medium for cell lines 267B-1 and BRFF-41T and approximately 10-fold more for the LNCaP cell line. The effect of SPBE dosing on these cell lines, is not irreversible, since a 30 min treatment with SPBE at an IC50 concentration does not inhibit their growth. Normal prostate cells were inhibited by 20-25% when grown in the presence of 200 nl SPBE equivalent per ml media. Growth of other non-prostatic cancer cell lines, i.e. Jurkat and HT-29, was affected by approx. 50% and 40%, respectively. When LNCaP cells Were grown in the presence of dihydrotestosterone and SPBE, the IC50 concentration decreased significantly compared to LNCaP cells grown in the presence of serum and SPBE. Reduced cellular growth after SPBE treatment of these cell lines may relate to decreased expression of Cox-2 and may be due to changes observed in the expression of Bcl-2. Expression of Cox-l under similar conditions is not affected because of its constitutive expression. Since increased Cox-2 expression is associated with an increased incidence of prostate cancer, and decrease in its expression by SPBE would provide a basis for further investigation of its use against BPH and in prostatic cancer chemoprevention. (C) 2001 Academic Press. C1 Boston Bioprod Inc, Ashland, MA 01721 USA. PharmaPrint Inc, Irvine, CA 92612 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sharma, CP (reprint author), Boston Bioprod Inc, 200 Homer Ave, Ashland, MA 01721 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 33 TC 27 Z9 28 U1 1 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2001 VL 25 IS 11 BP 1117 EP 1124 DI 10.1006/cbir.2001.0779 PG 8 WC Cell Biology SC Cell Biology GA 498RJ UT WOS:000172524000005 PM 11913955 ER PT J AU O'Neil, JJ Stegemann, JP Nicholson, DT Gagnon, KA Solomon, BA Mullon, CJP AF O'Neil, JJ Stegemann, JP Nicholson, DT Gagnon, KA Solomon, BA Mullon, CJP TI The isolation and function of porcine islets from market weight pigs SO CELL TRANSPLANTATION LA English DT Article DE porcine islets; islet transplantation; xenotransplantation; bioartificial pancreas ID BIOARTIFICIAL PANCREAS; MASS ISOLATION; DIABETIC RATS; XENOTRANSPLANTATION; IMMUNOSUPPRESSION; LANGERHANS; LIBERASE; CANINE AB The efficacy of clinical islet transplantation has been demonstrated with autografts, and although islet allografts have established insulin independence in a small number of IDDM patients, the treatment is confounded by the necessity of immunosuppression, the lack of donor tissue, and recurring islet immunogenicity. These limitations underscore a need to develop therapies to serve the large population of diabetic patients. Porcine islet xenotransplantation, together with a successful immune intervention strategy, may provide the necessary clinical alternative. However, a major obstacle in evaluating this approach has been the difficulty of obtaining adequate volumes of functional islet tissue from pigs. Donors of marker weight are preferable to retired breeders due to their abundance, lower animal and husbandry costs, and are more suitable to meet regulatory guidelines for donor tissue for xenotransplantation. We describe a simple isolation procedure that following purification yields a mean of 350,000 IE, corresponding to 179 units of insulin and 1.8 mg of DNA with an islet purity and Viability in excess of 85% (n = 317 isolations). In both short- and long-term cell cultures, porcine islets demonstrated glucose-responsive insulin secretion. However, this secretion is density dependent, which may have significant consequences in the development of immunoisolation technologies to support porcine islet xenotransplantation. Following implantation into diabetic nude mice, porcine islets remained functional in excess of 1 year. Implantation of a bioartificial pancreas containing porcine islets into pancreatectomized dogs provided significant, clinical benefit with an improved diabetic condition. Finally, secretagogue-induced insulin release was demonstrated in vitro from these devices after removal from immunocompetent recipients. Immunohistochemical staining identified well-granulated islets following long-term implantation in both the rodent and canine models. This study demonstrates the ability to isolate porcine islets in clinically relevant numbers from market animals, which survive and remain functional fur prolonged periods of time in an immune-deficient or immunoprotected environment. C1 Circe Biomed Inc, Lexington, MA 02421 USA. RP O'Neil, JJ (reprint author), Joslin Diabet Ctr, RISLE, 1 Joslin Pl, Boston, MA 02215 USA. NR 32 TC 50 Z9 50 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2001 VL 10 IS 3 BP 235 EP 246 PG 12 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 444JQ UT WOS:000169396700001 PM 11437069 ER PT J AU Roy, P Washizu, J Tilles, AW Yarmush, ML Toner, M AF Roy, P Washizu, J Tilles, AW Yarmush, ML Toner, M TI Effect of flow on the detoxification function of rat hepatocytes in a bioartificial liver reactor SO CELL TRANSPLANTATION LA English DT Article DE bioartificial liver; cytochrome P4501A1; detoxification; flow; mathematical model ID CYTOCHROME-P450; FAILURE AB Ethoxyresorufin-o-deethylation (EROD) can be used as a sensitive measure of hepatic detoxification function. In this study, we employed a fluorescence assay based on EROD to study the effect of varying Peclet number (or flow) on hepatic function in a microchannel flat-plate bioartificial liver (BAL) reactor containing a coculture of hepatocytes and fibroblasts. Static culture and reactor flow experiments established that: 1) a pseudo-steady-state detoxification rate could be attained at each Peclet number, 2) the steady-state detoxification rate increased nonlinearly with Peclet number (ranging from 167 to 2500), 3) the uptake rate of substrate was a linear function of cell surface substrate concentration (<1 muM), and 4) a shear stress of 10 dyne/cm(2) did not adversely affect hepatic function for at least 12 h. A convection-diffusion-reaction model supports the conclusion that increased convective mass transfer of substrate to the cell surface is the primary cause of the observed increase in EROD rate with Peclet number. Our results suggest that detoxification rates can be enhanced by an order of magnitude by choosing an appropriate Peclet number. For our bioreactor configuration, this optimum corresponds to a Peclet number range of 1000-2000 at a Damkohler number of 0.55. The usefulness of the mathematical model is discussed in the context of scale-up to a clinical BAL reactor for human application. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Bigelow 1401,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR13322]; NIDDK NIH HHS [DK43371] NR 22 TC 20 Z9 20 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2001 VL 10 IS 7 BP 609 EP 614 PG 6 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 487WU UT WOS:000171902700006 PM 11714195 ER PT J AU Glowacki, J AF Glowacki, J TI Engineered cartilage, bone, joints, and menisci - Potential for temporomandibular joint reconstruction SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT Workshop on Moving TMJ Research into the 21st Century CY MAY 22-23, 2000 CL FEDERAT AMER SOC EXPTL BIOL, BETHESDA, MARYLAND SP TMJ Assoc, NIAID, NICHHD HO FEDERAT AMER SOC EXPTL BIOL DE tissue engineering; temporomandibular joint; meniscus; cartilage; bone ID HUMAN INTERVERTEBRAL DISC; 3-DIMENSIONAL CULTURE; ARTICULAR-CARTILAGE; DEMINERALIZED BONE; EXPERIMENTAL-MODEL; IN-VITRO; CHONDROCYTES; REGENERATION; REPLACEMENT; FIBROBLASTS AB Reconstruction of many musculoskeletal structures can be accomplished by bone grafting and implantation of prostheses. Alternate approaches are needed, however, for repair of complex structures such as articular cartilage surfaces and the temporomandibular meniscus and joint. Tissue engineering, either cell-free or cell-based, offers promise because of recent advances in materials research and in our knowledge of the cellular and molecular mechanisms of tissue repair. There are th ree considerations in designing a construct for engineered tissue: the source of cells, if any; the nature of the carrier or scaffold; and use, if any, of genes, factors, or adjuvants. Autogenous cells, often expanded in vitro, have been useful for cartilage tissue engineering. Precursor/progenitor cells are advantageous for bone tissue. There are many natural and synthetic resorbable materials with good biocompatibility and tissue compatibility that can be modified to have the porosity and mechanical properties needed for specific applications. The scaffolds can also be modified to provide biological signals to augment repair and integration. Copyright (C) 2001 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Skeletal Biol Res Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Glowacki, J (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR 44873, AR 455870] NR 41 TC 20 Z9 22 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2001 VL 169 IS 3 BP 302 EP 308 DI 10.1159/000047895 PG 7 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 455CQ UT WOS:000170010300016 PM 11455127 ER PT B AU Endres, M Laufs, U Liao, JK Moskowitz, MA AF Endres, M Laufs, U Liao, JK Moskowitz, MA BE Choi, DW Dacey, RG Hsu, CY Powers, WJ TI HMG-CoA reductase inhibitors reduce cerebral infarct size by upregulating endothelial nitric oxide synthase SO CEREBROVASCULAR DISEASE: MOMENTUM AT THE END OF THE SECOND MILLENNIUM SE AMERICAN HEART ASSOCIATION MONOGRAPH SERIES LA English DT Proceedings Paper CT 21st Princeton Conference on Cerebrovascular Disease CY MAY 07-10, 1998 CL ST LOUIS, MO SP Washington Univ ID MICE; EXPRESSION; ISCHEMIA; CELLS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Endres, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU FUTURA PUBL CO INC PI ARMONK PA 135 BEDFORD RD PO BOX 418, ARMONK, NY 10504-0418 USA BN 0-87993-494-8 J9 AM HEART MONOGR S PY 2001 BP 101 EP 111 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA BT13Q UT WOS:000172045100007 ER PT B AU Ren, J Markman, J Finklestein, SP AF Ren, J Markman, J Finklestein, SP BE Choi, DW Dacey, RG Hsu, CY Powers, WJ TI Growth factors and stroke recovery SO CEREBROVASCULAR DISEASE: MOMENTUM AT THE END OF THE SECOND MILLENNIUM SE AMERICAN HEART ASSOCIATION MONOGRAPH SERIES LA English DT Proceedings Paper CT 21st Princeton Conference on Cerebrovascular Disease CY MAY 07-10, 1998 CL ST LOUIS, MO SP Washington Univ ID FOCAL CEREBRAL INFARCTION; SERINE/THREONINE KINASE RECEPTORS; ENHANCES FUNCTIONAL RECOVERY; RAT SYMPATHETIC NEURONS; OSTEOGENIC PROTEIN-1; HIPPOCAMPAL-NEURONS; BEHAVIORAL RECOVERY; NEOCORTICAL DAMAGE; PYRAMIDAL NEURONS; BRAIN-INJURY C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ren, J (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 50 TC 1 Z9 1 U1 0 U2 0 PU FUTURA PUBL CO INC PI ARMONK PA 135 BEDFORD RD PO BOX 418, ARMONK, NY 10504-0418 USA BN 0-87993-494-8 J9 AM HEART MONOGR S PY 2001 BP 393 EP 400 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA BT13Q UT WOS:000172045100027 ER PT J AU Cockrill, BA Kacmarek, RM Fifer, MA Bigatello, LM Ginns, LC Zapol, WM Semigran, MJ AF Cockrill, BA Kacmarek, RM Fifer, MA Bigatello, LM Ginns, LC Zapol, WM Semigran, MJ TI Comparison of the effects of nitric oxide, nitroprusside, and nifedipine on hemodynamics and right ventricular contractility in patients with chronic pulmonary hypertension SO CHEST LA English DT Article DE inotropism; nifedipine; nitric oxide; nitroprusside; pulmonary hypertension ID RESPIRATORY-DISTRESS-SYNDROME; CALCIUM-CHANNEL BLOCKERS; HEART-FAILURE; SMOOTH-MUSCLE; DYSFUNCTION; ARTERY; VASOCONSTRICTION; EPOPROSTENOL; PROSTACYCLIN; SURVIVAL AB Study objectives: The effects of inhaled nitric oxide (NO) on hemodynamics and right ventricular (RV) contractility were compared with those of nitroprusside and nifedipine in 14 patients with severe chronic pulmonary hypertension. Study design: Micromanometer and balloon-tipped right heart catheterization were performed. Inhaled NO, IV nitroprusside, and sublingual nifedipine were administered sequentially while patients breathed > 90% oxygen. Setting: Cardiac catheterization laboratory in a tertiary care teaching hospital. Patients: Fourteen patients with severe pulmonary hypertension unrelated to left ventricular dysfunction, Measurements and results: During NO inhalation, mean systemic arterial pressure (MAP) was unchanged, but pulmonary artery (PA) pressure ([mean +/- SEM] 49 +/- 2 mm Hg vs 44 +/- 2 mm Hg; p < 0.01), pulmonary vascular resistance (PVR; 829 +/- 68 vs 869 +/- 64 dyne . s . cm(-5); p < 0.01) and RV end-diastolic pressure (RVEDP; 12 +/- 1 vs 10 +/- 1 mm Hg; p < 0.01) decreased. Stroke volume index (SVI; 31 +/- 2 vs 35 +/- 3 mL/m(2); p < 0.05) increased, and the first derivative of RV pressure at 15 mm Hg developed pressure (RV +dP/dt at DP15) was unchanged. During nitroprusside administration, MAP decreased (105 +/- 5 vs 76 +/- 5 mm Hg; p < 0.01), PA was unchanged (48 +/- 2 vs 45 +/- 3 mm Hg; p not significant), and PVR decreased (791 +/- 53 vs 665 +/- 53 dyne.s.cm(-5); p < 0.01). RV +dP/dt at DP15 increased (425 +/- 22 vs 465 +/- 29 mm Hg/s; p < 0.05), but SVI was unchanged, Nifedipine decreased MAP (103 +/- 5 vs 94 +/- 5 mm Hg; p < 0.01), PA and PVR were unchanged, RVEDP increased (12 +/- 1 vs 14 +/- 2 mm Hg; p < 0.01), and RV +dP/dt at DP15 decreased (432 +/- 90 vs 389 +/- 21 mm Hg/s; p < 0.05). Conclusions: Inhaled NO is a selective pulmonary vasodilator in patients with chronic pulmonary hypertension that improves cardiac performance without altering RV contractility, Nitroprusside caused a similar degree of pulmonary vasodilation, In contrast to inhaled NO, nitroprusside caused systemic hypotension associated with an increase in RV contractility. Acute administration of nifedipine did not cause pulmonary vasodilation, but RVEDP increased and RV contractility decreased. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cockrill, BA (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL43297] NR 34 TC 32 Z9 34 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2001 VL 119 IS 1 BP 128 EP 136 DI 10.1378/chest.119.1.128 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 398QC UT WOS:000166766300024 PM 11157594 ER PT J AU Bostic, JQ Bagnell, A AF Bostic, JQ Bagnell, A TI Psychiatric school consultation - An organizing framework and empowering techniques SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article AB Psychiatric consultations, including techniques that empower school staff, are increasingly valuable. More collaborative roles with school staff will improve not only the success of individual students but also the redefinition of schools as they better address the future needs of their students. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bostic, JQ (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WAC 725, Boston, MA 02114 USA. NR 24 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2001 VL 10 IS 1 BP 1 EP + PG 13 WC Psychiatry SC Psychiatry GA 396GD UT WOS:000166627200003 PM 11214406 ER PT J AU Hicks, JM Haeckel, R Price, CP Lewandrowski, K Wu, AHB AF Hicks, JM Haeckel, R Price, CP Lewandrowski, K Wu, AHB TI Recommendations and opinions for the use of point-of-care testing for hospitals and primary care: summary of a 1999 symposium SO CLINICA CHIMICA ACTA LA English DT Review DE point-of care testing; glucose; arterial blood gases; cardiac markers; turnaround times; drugs-of-abuse testing ID BLOOD-GLUCOSE; GENERAL-PRACTICE; COST-ANALYSIS; PATIENT; EMERGENCY; MANAGEMENT; ACCURACY; IMPACT; TRIAL; TIME AB As part of a symposium on laboratory medicine, a colloquium on point-of-care testing was held in June 1999 where four experts were invited to produce recommendations and opinions on the use of point-of-care testing under various clinical venues. Each commented on costs for providing POCT services. A total of eleven recommendations and four opinions were rendered and discussed in an open forum. While one expert concluded that some forms of POCT are less expensive than central laboratory testing if entire laboratory workstations are eliminated, another expert suggested that POCT offered little advantage if rapid transport systems are available. A recommendation was made that POCT be considered for analytes that have a required reporting turnaround time of <30 min, and that the goals for precision and accuracy should be dictated by the clinical need and not by analytical limitations. Recommendations for POCT in specific clinical situations include use of glycated hemoglobin and urine albumin testing with personal glucose monitoring at the time of consultation, use of glycated albumin for gestational diabetes, leukocyte esterase and nitrite testing in urine to screen for urinary tract infections, coagulation tests for monitoring patients on oral anticoagulant therapy and in the operating room, testing for H. pylori for patients with dyspepsia, and cardiac markers and urine drugs-of-abuse testing in the emergency department. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Hartford Hosp, Dept Pathol & Lab Med, Ishikari, Hokkaido 06102, Japan. Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. St Bartholomews Hosp, Dept Clin Biochem, London E1 2AD, England. Royal London Sch Med & Dent, London E1 2AD, England. Inst Lab Med, D-28205 Bremen, Germany. Childrens Natl Med Ctr, Dept Lab Med, Washington, DC 20010 USA. George Washington Univ, Sch Med, Washington, DC 20010 USA. RP Hartford Hosp, Dept Pathol & Lab Med, Ishikari, Hokkaido 06102, Japan. EM awu@harthosp.org NR 55 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN PY 2001 VL 303 IS 1-2 BP 1 EP 17 DI 10.1016/S0009-8981(00)00400-9 PG 17 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 397MT UT WOS:000166700000001 PM 11163017 ER PT B AU Asch, DA Faber-Langendoen, K AF Asch, DA Faber-Langendoen, K BE VanderHeide, A OnwuteakaPhilipsen, B Emanuel, EJ VanderMaas, PJ VanderWal, G TI Sequencing the withdrawal of life-sustaining treatments SO CLINICAL AND EPIDEMIOLOGICAL ASPECTS OF END-OF-LIFE DECISION-MAKING SE KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN, VERHANDELINGEN LA English DT Proceedings Paper CT Colloquium on Clinical and Epidemiological Aspects of End-of-Life Decision-Making CY OCT 07-09, 1999 CL AMSTERDAM, NETHERLANDS SP Royal Netherlands Acad Arts & Sci, Netherlands Org Sci Res, Dutch Canc Soc, Dutch Minist Hlth, Erasmus Univ Rotterdam Fdn Vereniging Trustfonds, Vrije Univ Amsterdam, VanCoeverden Adriani Fdn & Dittmerfonds, Erasmus Univ Rotterdam, Dept Publ Hlth, Vrije Univ Amsterdam, Fac Med ID PERTUSSIS VACCINATION; DECISION-MAKING; PHYSICIANS; SUPPORT; EUTHANASIA; ATTITUDES; CARE; OMISSION; LIMITS; PREFER AB Previous studies have demonstrated that when patients are withdrawn from life-sustaining treatments, these treatments are often withdrawn sequentially, rather than all at once. We observed the sequence of withdrawing life support among 211 consecutive patients dying in four Midwestern United States hospitals from whom at least one of eight specific life-sustaining treatments was or could have been withdrawn. We used a parametric statistical technique to explain the order in which these forms of life support were withdrawn in terms of a set of previously determined characteristics of the forms of life support including, among other characteristics, their cost, scarcity, and discomfort. We found a distinct sequence in which the eight forms of life support were withdrawn in this clinical sample. The observed order was, from earliest to latest: blood products, hemodialysis, vasopressors, mechanical ventilation, total parenteral nutrition, antibiotics, intravenous fluids, tube feedings (p < 0.0001). This sequence is almost identical to that observed in a previous study based on hypothetical scenarios. Those forms of life support perceived as more artificial, scarce, or expensive were withdrawn earlier than those with less of these characteristics. We conclude that the preference for withdrawing some forms of life-sustaining treatments over others is associated with intrinsic characteristics of the forms of life-sustaining treatments themselves. Once the decision has been made to forgo life-sustaining treatment, the process used remains complex and appears to target many different goals simultaneously. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. RP Asch, DA (reprint author), Vet Affairs Med Ctr, Philadelphia, PA USA. NR 28 TC 0 Z9 0 U1 1 U2 2 PU ROYAL NETHERLANDS ACADEMY ARTSSCIENCES PI AMSTERDAM PA OUDE HOOGSTRAAT 24 PO BOX 19121, 1000 GC AMSTERDAM, NETHERLANDS BN 90-6984-309-9 J9 KNAW VERHAN PY 2001 VL 102 BP 25 EP 37 PG 5 WC Medical Ethics; Medicine, General & Internal SC Medical Ethics; General & Internal Medicine GA BU30Q UT WOS:000175616200003 ER PT B AU Pearlman, RA Starks, H Cain, KC Cole, WG Patrick, DL Uhlmann, RF AF Pearlman, RA Starks, H Cain, KC Cole, WG Patrick, DL Uhlmann, RF BE VanderHeide, A OnwuteakaPhilipsen, B Emanuel, EJ VanderMaas, PJ VanderWal, G TI Integrating preferences for life-sustaining treatments and health states ratings into meaningful advance care discussions SO CLINICAL AND EPIDEMIOLOGICAL ASPECTS OF END-OF-LIFE DECISION-MAKING SE KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN, VERHANDELINGEN LA English DT Proceedings Paper CT Colloquium on Clinical and Epidemiological Aspects of End-of-Life Decision-Making CY OCT 07-09, 1999 CL AMSTERDAM, NETHERLANDS SP Royal Netherlands Acad Arts & Sci, Netherlands Org Sci Res, Dutch Canc Soc, Dutch Minist Hlth, Erasmus Univ Rotterdam Fdn Vereniging Trustfonds, Vrije Univ Amsterdam, VanCoeverden Adriani Fdn & Dittmerfonds, Erasmus Univ Rotterdam, Dept Publ Hlth, Vrije Univ Amsterdam, Fac Med ID CARDIOPULMONARY-RESUSCITATION; ELDERLY PATIENTS; DIRECTIVES; PHYSICIANS; PREDICTIONS; JUDGMENTS; WORSE; DEATH AB Advance care planning tries to ensure that decision-making for decisionally incapacitated patients is patient-centered. This has particular relevance for end-of-life decisions. Although many people in the United States favor advance care planning, only a minority prepares advance directives. One impediment to clinician encouragement and involvement is not knowing how to discuss these issues. To help frame advance care planning discussions, we studied the interrelationships between treatment preferences and health state ratings of patients and well adults. The study population included a diverse sample of well adults and patients (n=342). Six treatment preferences were elicited in current health and two hypothetical states describing permanent coma and severe dementia. The six treatments were antibiotics, long-term hemodialysis, short-term mechanical ventilation, cardiopulmonary resuscitation (CPR), long-term jejunal feeding tube, and long-term mechanical ventilation. When participants declined noninvasive treatments, they usually declined more invasive treatments, and when they wanted to receive invasive treatments, they usually accepted less invasive ones. The data suggest an empirically derived, organizing sequence of treatments that represent increasing degrees of 'aggressiveness' that is influenced by invasiveness and treatment duration. CPR was in the mid-range of aggressiveness, and preferences for CPR were poor predictors of other treatment preferences. These results suggest that eliciting preferences for only CPR is not sufficient information to infer a patient's preferences for more invasive or long-term life-sustaining treatments. In addition, knowing that patients want treatment in their current health does not generalize well to wanting treatment in more impaired functional health states. Lastly, refusing treatment in severely impaired states of health, such as severe dementia or permanent coma, does not generalize well to refusing treatment in less impaired states of health. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Pearlman, RA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. NR 33 TC 0 Z9 0 U1 1 U2 1 PU ROYAL NETHERLANDS ACADEMY ARTSSCIENCES PI AMSTERDAM PA OUDE HOOGSTRAAT 24 PO BOX 19121, 1000 GC AMSTERDAM, NETHERLANDS BN 90-6984-309-9 J9 KNAW VERHAN PY 2001 VL 102 BP 39 EP 53 PG 5 WC Medical Ethics; Medicine, General & Internal SC Medical Ethics; General & Internal Medicine GA BU30Q UT WOS:000175616200004 ER PT J AU Pozzi, N Gaetaniello, L Martire, B De mattia, D Balestrieri, B Cosentini, E Schlossman, SF Duke-Cohan, JS Pignata, C AF Pozzi, N Gaetaniello, L Martire, B De mattia, D Balestrieri, B Cosentini, E Schlossman, SF Duke-Cohan, JS Pignata, C TI Defective surface expression of attractin on T cells in patients with common variable immunodeficiency (CVID) SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE common variable immunodeficiency; T cell activation; signal transduction; attractin ID DIPEPTIDYL PEPTIDASE-IV; B-CELLS; ANTIGEN RECEPTOR; DPPT-L; LYMPHOCYTES; ACTIVATION; DISEASES; CD26; DIFFERENTIATION; IMMUNOGLOBULIN AB The proliferative responses of T lymphocytes of a subset of patients with CVID are abnormally low. This may be due to abnormalities in extracellular interactions or signalling defects downstream from membrane-associated receptors. Demonstrating that the T cell receptor signalling was normal, we observed no abnormal pattern of activation-induced tyrosine phosphorylation in cells from CVID patients. Moreover, the addition of exogenous IL-2 increased the low proliferation to mitogens, thus indicating the integrity of the IL-2R signalling apparatus. Attractin is a rapidly expressed T cell activation antigen involved in forming an association between T cells and monocytes. Twenty-four to 48 h after activation by CD3 cross-linking, attractin expression was not up-regulated on the cells of CVID patients despite normal up-regulation of CD25 and CD26. On control cells, however, attractin expression was up-regulated together with CD25 and CD26. The addition of the purified 175-kD attractin was capable of restoring the proliferative response of peripheral blood mononuclear cells following CD3 X-L in the presence of suboptimal concentrations of rIL-2 (10 and 20 U/ml). The effect was dose-dependent with the maximal effect at a concentration of 500 ng/ml, and present at a concentration as low as 50 ng/ml. Due to the likely role of attractin in cell guidance and amplification of the immune response, our results indicate that the lack of up-regulation of the molecule in patients with CVID may in turn affect any further step of productive immune response. Our finding may also imply a potential therapeutic role for this novel molecule. C1 Univ Naples Federico II, Dept Paediat, Immunol Unit, I-80131 Naples, Italy. Univ Naples Federico II, Immunohaematol Unit, I-80131 Naples, Italy. Univ Bari, Dept Paediat, Bari, Italy. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Pignata, C (reprint author), Univ Naples Federico II, Dept Paediat, Immunol Unit, Via S Pansini 5, I-80131 Naples, Italy. RI Pignata, Claudio/O-2466-2013; Duke-Cohan, Jonathan/A-5812-2010 OI Pignata, Claudio/0000-0003-1568-9843; Duke-Cohan, Jonathan/0000-0002-9478-9609 FU Telethon [E.0934] NR 27 TC 23 Z9 24 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2001 VL 123 IS 1 BP 99 EP 104 DI 10.1046/j.1365-2249.2001.01413.x PG 6 WC Immunology SC Immunology GA 396HT UT WOS:000166630800016 PM 11168005 ER PT J AU Mozaffarian, D Caldwell, JH AF Mozaffarian, D Caldwell, JH TI Right ventricular involvement in hypertrophic cardiomyopathy: A case report and literature review SO CLINICAL CARDIOLOGY LA English DT Review DE hypertrophic cardiomyopathy; light ventricle; review ID CLINICAL MANIFESTATIONS; PATHO-PHYSIOLOGY; FEATURES; ECHOCARDIOGRAPHY; INTERRELATIONS; OBSTRUCTION; THERAPY AB Although hypertrophic cardiomyopathy (HCM) is classically considered a disease of the left ventricle, right ventricular (RV) abnormalities have also been reported. However, involvement of the right ventricle in HCM has not been extensively characterized. The literature regarding prevalence, genetics, patterns of involvement, histologic findings, symptoms, diagnosis, and treatment of RV abnormalities in HCM is reviewed. To highlight the salient points, a case is presented of apical HCM with significant RV involvement, with an RV outflow tract gradient and near obliteration of the RV cavity, in the absence of a left intraventricular gradient. Right ventricular involvement in HCM appears to be as heterogeneous as that of the left ventricle. The spectrum extends from mild concentric hypertrophy to more unusual severe, obstructive disease. While in some cases the extent of RV involvement correlates with left ventricular (LV) involvement, predominant RV disease can be seen as well. While the genetics of RV involvement have not been well characterized, histologic findings appear to be similar to those in the left ventricle, suggesting similar pathogenesis. Significant RV involvement may result in RV outflow obstruction and/or reduced RV diastolic filling, with potentially increased incidence of severe dyspnea, supra ventricular arrhythmias, and pulmonary thromboembolism. The optimal treatment for patients with significant RV disease is unknown. Medical and surgical therapies have been attempted with variable success; experience with newer techniques such as percutaneous catheter ablation has not been reported. Further characterization of RV involvement in HCM is necessary to elucidate more clearly the clinical features and optimal treatments of this manifestation of HCM. C1 Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Mozaffarian, D (reprint author), Univ Washington, Div Cardiol, 1959 NE Pacific St,Box 356422, Seattle, WA 98195 USA. RI Mozaffarian, Dariush/B-2276-2008 NR 22 TC 16 Z9 17 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JAN PY 2001 VL 24 IS 1 BP 2 EP 8 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 387UD UT WOS:000166139500002 PM 11195601 ER PT J AU Philbin, EF McCullough, PA Dec, GW DiSalvo, TG AF Philbin, EF McCullough, PA Dec, GW DiSalvo, TG TI Length of stay and procedure utilization are the major determinants of hospital charges for heart failure SO CLINICAL CARDIOLOGY LA English DT Article DE congestive heart failure; outcomes; hospital charges; length of stay ID EARLY READMISSION; OUTCOMES; CARE; INFORMATION; VALIDATION; QUALITY AB Background: Most of the 10 billion dollars spent annually on heart failure (HF) management in this country is attributed to hospital charges. There an widespread efforts to decrease the costs of treating this disorder, both by preventing hospital admissions and reducing lengths of stay (LOS). Hypothesis: The objective of this study was to identify the major determinants of hospital charges for an acute hospitalization for HF among a large, diverse group of patients. Methods: Administrative information on all 1995 New York State hospital discharges assigned ICD-9-CM codes indicative of HF in the principal diagnosis position were obtained. Bivariate and multivariate statistical analyses were utilized to determine those patient- and hospital-specific characteristics which had the greatest influence on hospital charges. Results: In all, 43,157 patients were identified. Mean hospital charges were $11,507 +/- 15,995 and mean hospital LOS was 9.6 +/- 11.5 days. With multivariate analyses, the most significant independent predictors of higher hospital charges were longer LOS, admission to a teaching hospital, treatment in an intensive care unit, and the utilization of cardiac surgery, permanent pacemakers, and mechanical ventilation. Age, gender, race, comorbidity score, and medical insurance, as well as treatment by a cardiologist and death during the index hospitalization were not among the most significant predictors. Conclusions: We conclude that LOS and procedure utilization are the major determinants of hospital charges for an acute episode of inpatient HF care. Reducing LOS and other initiatives to restructure hospital-based HF care map reduce total health care costs for HF. C1 Henry Ford Hosp, Sect Heart Failure & Cardiac Transplantat, Detroit, MI 48202 USA. Henry Ford Hosp, Div Cardiovasc Med, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Cardiac Unit, Heart Failure & Transplantat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Philbin, EF (reprint author), Albany Med Coll MC44, George E Pataki Chair Cardiol, 47 New Scotland Ave, Albany, NY 12208 USA. NR 27 TC 17 Z9 17 U1 0 U2 1 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JAN PY 2001 VL 24 IS 1 BP 56 EP 62 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 387UD UT WOS:000166139500011 PM 11195608 ER PT J AU Hadigan, C Meigs, JB Corcoran, C Rietschel, P Piecuch, S Basgoz, N Davis, B Sax, P Stanley, T Wilson, PWF D'Agostino, RB Grinspoon, S AF Hadigan, C Meigs, JB Corcoran, C Rietschel, P Piecuch, S Basgoz, N Davis, B Sax, P Stanley, T Wilson, PWF D'Agostino, RB Grinspoon, S TI Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CORONARY HEART-DISEASE; ANTIRETROVIRAL THERAPY HAART; BETA-CELL FUNCTION; GLUCOSE-TOLERANCE; INSULIN-RESISTANCE; PROTEASE INHIBITORS; WOMEN; FAT; MODEL; HYPERLIPIDEMIA AB We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Infect Dis Unit, Cambridge, MA USA. Framingham Heart Study, Framingham, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR300088]; NIDDK NIH HHS [R01-DK54167, R01-DK59535] NR 40 TC 441 Z9 454 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2001 VL 32 IS 1 BP 130 EP 139 DI 10.1086/317541 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385PF UT WOS:000166012300017 PM 11118392 ER PT J AU Brown, RH Ross, CA AF Brown, RH Ross, CA TI Introduction to the 1999 Annual Conference Manuscripts - Genetic aspects of psychiatric and neurological disorders SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Editorial Material C1 Harvard Univ, Sch Med, Day Neuromuscular Res Lab,Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Sch Med, Mol Neurobiol Lab, Dept Psychiat, Baltimore, MD 21205 USA. RP Brown, RH (reprint author), Harvard Univ, Sch Med, Day Neuromuscular Res Lab,Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JAN PY 2001 VL 1 IS 1-2 BP 82 EP 83 AR PII S1566-2772(00)00022-0 DI 10.1016/S1566-2772(00)00022-0 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529EZ UT WOS:000174288200013 ER PT J AU Brown, RH AF Brown, RH TI Amyotrophic lateral sclerosis: lessons from mouse and human genetics SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE amyotrophic lateral sclerosis; superoxide dismutase ID CU,ZN SUPEROXIDE-DISMUTASE; FAMILIAL SPASTIC PARAPLEGIA; SPINAL MUSCULAR-ATROPHY; MOTOR-NEURON DISEASE; INCREASED 3-NITROTYROSINE; GLUTAMATE TRANSPORTER; LOCUS HETEROGENEITY; TYROSINE NITRATION; HYDROGEN-PEROXIDE; OXIDATIVE DAMAGE AB Amyotrophic lateral sclerosis (ALS) is a progressive, uniformly fatal, adult-onset degenerative disorder of motor neurons. It is now clear that cases arise as dominant traits because of mutations in a gene encoding the cytosolic, Cu/Zn superoxide dismutase (SOD1). Several lines of evidence favor the view that the mutations con fer one or more no urotoxic properties on the mutant protein. The mechanisms whereby mSOD I is cytotoxic are unknown. However, several observations are relevant, (1) The mutant SOD1 proteins are con formationally less stable than the wild-type protein, with reduced affinity for zinc and a more readily reducible copper ion, This may lead directly (via metal toxicity) or indirectly (via altered binding properties of the mutant SODI protein or protein aggregation) to neurotoxicity. (2) Many of the mutants hake an enhanced capacity to promote nitrotyrosine formation or act as oxidases. (3) In most cases of human and murine ALS, there is increased oxidative pathology, (4) In ALS mice, axonal transport and mitochondrial function are impaired. (5)The importance of axonal transport, and the neuronal cytoskeleton more generally is emphasized by the observation that rare cases of ALS are associated with mutations in the neurofilament heady subunit gene. (6) Both in mSOD1-mediated and sporadic ALS. data implicate glutamate excitotoxicity as a disease-accelerating factor. Taken together, these consideration,, suggest a model in which multiple events act in concert to triggerdeath in motor neurons. A downstrearn consequence is late-stage activation of cell death genes. This model has significant implications for the development of therapeutic strategies for ALS and related disorders. (C) 2001 Published by Assocation lot Research in Nervous and Mental Disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Neuromuscular Res Lab,Dept Neurol, Boston, MA 02114 USA. RP Brown, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Neuromuscular Res Lab,Dept Neurol, Boston, MA 02114 USA. NR 92 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JAN PY 2001 VL 1 IS 1-2 BP 84 EP 90 AR PII S1566-2772(00)00017-7 DI 10.1016/S1566-2772(00)00017-7 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529EZ UT WOS:000174288200014 ER PT J AU Cannon, SC AF Cannon, SC TI Voltage-gated ion channelopathies of the nervous system SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE ion channel; periodic paralysis; myotonia; epilepsy; headache ID HYPOKALEMIC PERIODIC PARALYSIS; FAMILIAL HEMIPLEGIC MIGRAINE; POTASSIUM CHANNEL GENE; MUSCLE SODIUM-CHANNEL; EPISODIC ATAXIA TYPE-2; CALCIUM-CHANNEL; MYOTONIA-CONGENITA; CHLORIDE CHANNEL; PARAMYOTONIA-CONGENITA; GENERALIZED EPILEPSY AB Mutations in genes coding for voltage-gated ion channels cause a diverse group of disorders affecting heart, skeletal muscle, and brain. Mutant channels alter the electrical excitability of cells. which increases the susceptibility, to paroxysmal symptoms including cardiac arrhythmia. periodic paralysis. myotonia, seizures. migraine headache. and episodic ataxia. This review provides an update on the genetics and physiology of diseases of skeletal muscle and brain caused h mutations in voltage-gated in ion channel genes. The discovery of specific ion channel defects provides a rational basis for designing pharmacological intervention, as ion channel,, are the molecular targets of many drugs in clinical use. Moreover, the advent of a molecular genetic-based diagnosis provides an important tool for clarifying the natural history and effectiveness of intervention in these disorders. (C) 2001 Association for Research in Nervous and Mental Disease. All rights reserved. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, EDR 413, Boston, MA 02114 USA. RP Cannon, SC (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. NR 67 TC 19 Z9 20 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JAN PY 2001 VL 1 IS 1-2 BP 104 EP 117 AR PII S1566-2772(00)00011-6 DI 10.1016/S1566-2772(00)00011-6 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529EZ UT WOS:000174288200016 ER PT J AU Sorger, JI Hornicek, FJ Zavatta, M Menzner, JP Gebhardt, MC Tomford, WW Mankin, HJ AF Sorger, JI Hornicek, FJ Zavatta, M Menzner, JP Gebhardt, MC Tomford, WW Mankin, HJ TI Allograft fractures revisited SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Musculoskeletal-Tumor-Society CY MAY, 1999 CL DENVER, COLORADO SP Musculoskeletal Tumor Soc ID FEMORAL ALLOGRAFTS; BONE; RECONSTRUCTION; REPLACEMENT; PROSTHESES AB A retrospective review of patients with allograft fractures was done at the authors' institution. Between 1974 and 1998, 185 of 1046 (17.7%) structural allografts fractured in 183 patients at a mean of 3.2 years after transplantation. Initial allograft fixation included internal fixation with plates and screws in 181 patients. Patients with grafts that were longer than the average length (15.5 cm) tended to have worse results. Adjuvant therapy had no effect on fracture rate. Seventy-three patients with fractures had other allograft complications. Infection and nonunion with allograft fracture significantly worsened the outcome. The incidence of fracture in the patients with osteoarticular and arthrodesis transplants was significantly higher than those patients who had intercalary and composite reconstructions. Treatment of the allograft fractures included open reduction and internal fixation in 41 patients, reconstruction with a new allograft in 38, allograft-prosthesis composite in five, oncologic prosthesis in 19, amputation in 15, arthroscopic removal of loose bodies in three, resurfacing of fractured osteoarticular allograft surfaces in 39, allograft removal and cement spacer placement in 15. Twenty patients did not receive treatment. Eight of the fractures in patients who were not treated healed spontaneously. Outcomes were judged as excellent in nine patients (4.9%), good in 72 patients (38.9%), fair in 17 patients (9.2%), and in 85 patients (45.9%) the allograft reconstruction failed. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Oncol Unit, Boston, MA 02114 USA. Boston Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hornicek, FJ (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Oncol Unit, 55 Fruit St,GRB 604, Boston, MA 02114 USA. NR 23 TC 68 Z9 76 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2001 IS 382 BP 66 EP 74 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 388NL UT WOS:000166187100011 PM 11154007 ER PT J AU Hornicek, FJ Gebhardt, MC Tomford, WW Sorger, JI Zavatta, M Menzner, JP Mankin, HJ AF Hornicek, FJ Gebhardt, MC Tomford, WW Sorger, JI Zavatta, M Menzner, JP Mankin, HJ TI Factors affecting nonunion of the allograft-host junction SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Musculoskeletal-Tumor-Society CY MAY, 1999 CL DENVER, COLORADO SP Musculoskeletal Tumor Soc ID BONE; RECONSTRUCTION; METHOTREXATE; RATS AB Nonunion of allograft-host junction after bone transplantation is not uncommon, and its treatment frequently is problematic. To improve the understanding of these nonunions, a retrospective review was performed of 163 nonunions in 945 patients who underwent allograft transplantation (17.3%) for various benign and malignant tumors at the authors' institution between 1974 and 1997. Of these 945 patients, 558 did not receive adjuvant therapy. Chemotherapy was administered to 354 patients and only 33 patients received radiation therapy alone. Seventy-one patients had radiation treatment and chemotherapy. Of the 163 patients who had nonunion develop at the allograft-host junction, there were 269 reoperations performed on the involved extremity. In 108 patients, treatment was successful resulting in union of the allograft-host junction. Forty-nine patients did not respond to multiple surgical treatment attempts. The greater the number of surgical procedures, the worse the outcome. The rate of nonunions increased to 27% for the patients who received chemotherapy as compared with 11% for the patients who did not receive chemotherapy. The order of allografts from highest rate of nonunion to lowest was as follows: alloarthrodesis, intercalary, osteoarticular, and alloprosthesis. Infection and fracture rates were higher in the patients with nonunions as compared with the patients without nonunions. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Oncol Unit, Boston, MA 02114 USA. Boston Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hornicek, FJ (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Oncol Unit, 55 Fruit St,GRB 604, Boston, MA 02114 USA. NR 22 TC 145 Z9 157 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2001 IS 382 BP 87 EP 98 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 388NL UT WOS:000166187100014 PM 11154010 ER PT J AU Chin, KR Mankin, HJ Gebhardt, MC AF Chin, KR Mankin, HJ Gebhardt, MC TI Primary osteosarcoma of the distal femur in two consecutive brothers SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SARCOMAS; BONE; GENE; MUTATIONS; CHILDREN; CANCER; FAMILY AB The following report describes two consecutive brothers from a nonimmigrant family, with no identifiable predisposing factors, who presented with osteosarcomas of their distal femurs, one at the age of 18 years and the other at the age of 21 years. Until a cost-effective program is developed to screen for osteosarcoma, a detailed family history should be obtained from every new patient with osteosarcoma and parents should be urged to schedule early evaluations of siblings with complaints of painful extremities. Increased frequency of cytogenetic studies to screen for genetic abnormalities in patients with osteosarcoma is recommended to help elucidate the cause of osteosarcoma. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg Oncol, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chin, KR (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg Oncol, GRB 606, Boston, MA 02114 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2001 IS 382 BP 191 EP 196 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 388NL UT WOS:000166187100026 PM 11153987 ER PT J AU Schneider, NG Olmstead, RE Franzon, MA Lunell, E AF Schneider, NG Olmstead, RE Franzon, MA Lunell, E TI The nicotine inhaler - Clinical pharmacokinetics and comparison with other nicotine treatments SO CLINICAL PHARMACOKINETICS LA English DT Review ID PLACEBO-CONTROLLED-TRIAL; POSITRON EMISSION TOMOGRAPHY; TOBACCO WITHDRAWAL SYMPTOMS; SMOKE-FREE CIGARETTES; NASAL SPRAY; DOUBLE-BLIND; ABUSE LIABILITY; VAPOR INHALER; CHEWING-GUM; TRANSDERMAL NICOTINE AB Nicotine inhaled in smoke is the most rapid form of delivery of the drug. With smoking, arterial boli and high venous blood nicotine concentrations are produced within seconds and minutes. respectively. The potency of nicotine as the primary reinforcement in tobacco addiction is attributed to this rapid rate of delivery. By design, nicotine treatments reduce the rate and extent of drug delivery for weaning from nicotine during smoking cessation. Theoretically, they prevent relapse by reducing withdrawal and craving associated with the abrupt cessation of cigarettes. The nicotine inhaler treats the complexity of smoking through weaning both from the drug and from the sensory/ritual components associated with smoking. The inhaler is 'puffed' but not lit and there is considerable 'puffing' required to achieve slower rising and lower nicotine concentrations. These factors allow it to be used as a nicotine reduction treatment. One inhaler contains 10mg of nicotine (and 1mg of menthol) of which 4mg of nicotine can be extracted and 2mg are systemically available. Shallow or deep 'puffing' results in similar nicotine absorption. Nicotine is delivered mainly to the oral cavity, throat and upper respiratory tract with a minor fraction reaching the lungs. This was confirmed with positron emission tomography and by assessment of arterial concentrations. A single inhaler can be used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per inhaler. With controlled puffing in laboratory testing, venous plasma nicotine concentrations from a single inhaler puffed 80 times over 20 minutes averaged 8.1 mug/L at 30 minutes. Lower concentrations of 6.4 to 6.9 mug/L have been reported for self-administration under clinical conditions. The time to peak plasma concentrations varies but is always significantly longer than with cigarette delivery. Estimates of nicotine intake from cotinine concentrations were higher than expected (60 to 70% of baseline smoking concentrations). This elevation may be due to the swallowing of nicotine and subsequent first-pass biotransformation to cotinine. In general. venous blood nicotine concentrations are considerably lower than with smoking and are within the range observed for other nicotine reduction therapies. Efficacy trials show consistent superiority of the inhaler over placebo. Despite the 'cigarette-like' appearance of the inhaler and the associated sensory/ritual elements. little treatment dependence or abuse has been reported. This is attributed to the slow rise time and low nicotine blood concentrations. The inhaler is a valuable addition to treatment of tobacco dependence and can be used alone or with other treatments. C1 VA Greater Los Angeles Hlth Care Syst, Nicotine Res Unit, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Pharmacia Consumer Hlth Care, Bridgewater, NJ USA. Univ Hosp, Dept Clin Pharmacol, Lund, Sweden. RP Schneider, NG (reprint author), VA Greater Los Angeles Hlth Care Syst, Nicotine Res Unit, Bldg 210,2nd Floor,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDA NIH HHS [DA11398] NR 118 TC 69 Z9 71 U1 2 U2 12 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2001 VL 40 IS 9 BP 661 EP 684 DI 10.2165/00003088-200140090-00003 PG 24 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 479MZ UT WOS:000171409300003 PM 11605715 ER PT S AU Baldessarini, RJ Tondo, L Hennen, J AF Baldessarini, RJ Tondo, L Hennen, J BE Hendin, H Mann, JJ TI Treating the suicidal patient with bipolar disorder - Reducing suicide risk with lithium SO CLINICAL SCIENCE OF SUICIDE PREVENTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Suicide Prevention 2000 Conference CY MAY 07-08, 2000 CL NEW YORK, NEW YORK SP Amer Fdn Suicide Prevent DE bipolar disorder; depression; lithium; maintenance treatment; manic-depressive disorders; mortality rates; suicide ID MANIC-DEPRESSIVE DISORDERS; RECURRENT MOOD DISORDERS; MAINTENANCE TREATMENT; MAJOR DEPRESSION; MORTALITY; BEHAVIOR; PROPHYLAXIS; PREVENTION; POPULATION; ILLNESS AB Bipolar disorder is associated with increased mortality because of complications of commonly comorbid substance use and stress-sensitive medical disorders as well as accidents and very high rates of suicide. Longterm lithium treatment may be associated with reduced Suicidal risk. We review and summarize findings that help to quantify relationships between the presence versus the absence of lithium maintenance and suicides or attempts in patients with bipolar or other major affective disorders. Results from 33 studies (1970-2000) yielded 13-fold lower rates of suicide and reported attempts during long-term lithium treatment than without it or after it was discontinued. Although greatly reduced, these rates remain above those estimated for the general population. Evidence for substantial, if incomplete, protection against suicide with lithium is supported by more compelling evidence than that for any other treatment provided for patients with mood disorders. Studies of commonly used, but incompletely evaluated, alternative treatments are required, and further protection against premature mortality can be anticipated with better protection against bipolar depression. C1 Harvard Univ, Sch Med, Int Consortium Res Biopolar Disorders, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Neurosci Program, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Psychot Disorders Program, Belmont, MA 02478 USA. Univ Cagliari, Dept Psychol, Cagliari, Sardinia, Italy. Lucio Bini Stanley Fdn Int Res Ctr, Cagliari, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370] NR 80 TC 71 Z9 72 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-330-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 932 BP 24 EP 43 PG 20 WC Multidisciplinary Sciences; Psychiatry SC Science & Technology - Other Topics; Psychiatry GA BT11J UT WOS:000172009800003 PM 11411189 ER PT S AU Maltsberger, JT AF Maltsberger, JT BE Hendin, H Mann, JJ TI Treating the suicidal patient - Basic principles SO CLINICAL SCIENCE OF SUICIDE PREVENTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Suicide Prevention 2000 Conference CY MAY 07-08, 2000 CL NEW YORK, NEW YORK SP Amer Fdn Suicide Prevent DE countertransference; psychotherapy; suicide; transference AB Successful psychotherapy with suicidal patients requires an emotionally full, active engagement from the therapist with his patient. Emphasis is on the real relationship, not the transference, and the therapist must be available to the patient as a sturdy, reliable object with whom to identify. The therapist's attitude must be loving, not neutral; the alliance is built upon the therapist's devotion to the patient's growth and the development of the attributes necessary for successful autonomous adult functioning. Patients require emotional containment and support, assistance in modulating painful affect, validation, education, help with reality testing, and kindly limit setting. Countertransference reactions must be expected and kept in check, so that the therapist does not get in the patient's way as he tries to build up the faulty mental structures that got him into trouble in the first place. C1 Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Dept Psychiat, Brookline, MA 02146 USA. RP Maltsberger, JT (reprint author), 38 Fuller St, Brookline, MA 02446 USA. NR 14 TC 6 Z9 6 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-330-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 932 BP 158 EP 168 PG 11 WC Multidisciplinary Sciences; Psychiatry SC Science & Technology - Other Topics; Psychiatry GA BT11J UT WOS:000172009800011 PM 11411184 ER PT J AU Rubin, RH AF Rubin, RH TI Gastrointestinal infectious disease complications following transplantation and their differentiation from immunosuppressant-induced gastrointestinal toxicities SO CLINICAL TRANSPLANTATION LA English DT Article DE GI infection; transplantation; immunosuppression ID MYCOPHENOLATE-MOFETIL; LIVER-TRANSPLANTATION; RENAL-TRANSPLANTATION; LONG-TERM; COMBINATION; RECIPIENTS; SAFETY AB It is often very difficult to distinguish between infection-related and immunosuppression-related gastrointestinal (GI) complications after transplantation. The risk of infection itself is determined by the patient's net state of immunosuppression as well as the presence of anatomic or technical abnormalities and the patient's epidemiological exposures. Of the anatomic abnormalities, diverticulitis is a particular problem in transplant patients, with a high rate of perforation and abscess formation. The causes of infectious disease syndromes are very different immediately after, early after, and late after transplantation. Infection during the first month may result from a pre-existing infection in the donor or recipient, or from the surgical wound, endotracheal tube, vascular access or drainage. During 1-6 months after transplantation, viruses attack and, with sustained immunosuppression, make opportunistic infections possible. Beyond 6 months after transplantation. the 80% of patients with good result from the transplant are at risk primarily for community-acquired microbes, including such enteric pathogens as Salmonella. Of the remaining patients. 10% have chronic viral infections and the 10%, who have poor allograft function are at greatest risk for opportunistic infection. This time line is helpful in determining whether a GI complication is likely to be related to infection rather than a specific effect of an immunosuppressant drug. Fever, inflammatory cells in the stool, abnormalities on endoscopy or computed tomography and leukocytosis can be useful in the diagnosis but are inconsistent markers for an infectious cause. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rubin, RH (reprint author), Massachusetts Gen Hosp, GRB 858,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 34 Z9 38 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PY 2001 VL 15 SU 4 BP 11 EP 22 DI 10.1111/j.1399-0012.2001.00011.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 442HN UT WOS:000169279300003 PM 11778782 ER PT J AU Yao, JK Reddy, RD van Kammen, DP AF Yao, JK Reddy, RD van Kammen, DP TI Oxidative damage and schizophrenia - An overview of the evidence and its therapeutic implications SO CNS DRUGS LA English DT Review ID ESSENTIAL FATTY-ACIDS; MAGNETIC-RESONANCE SPECTROSCOPY; MEMBRANE PHOSPHOLIPID-METABOLISM; SUPEROXIDE-DISMUTASE ACTIVITY; ANTIOXIDANT DEFENSE SYSTEM; GAMMA-AMINOBUTYRIC ACID; EXCITOTOXIC CELL-DEATH; FUNCTIONAL LIFE-SPAN; TARDIVE-DYSKINESIA; VITAMIN-E AB Free radicals are highly reactive chemical species generated during normal metabolic processes, which in excess can lead to membrane damage. Elaborate antioxidant defence systems exist to protect against oxidative stress. There is accumulating evidence of altered antioxidant capacity in schizophrenia. Membrane dysfunction can be secondary to free radical-mediated pathology. and may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment. Specifically. free radical-mediated abnormalities may contribute to the development of a number of clinically significant consequences, including prominent negative symptoms, tardive dyskinesia, neurological 'soft' signs and parkinsonian symptoms. Our previous results showing altered membrane dynamics and antioxidant enzyme activities in schizophrenia, and findings from other investigators, are consistent with the notion of free radical-mediated neurotoxicity in schizophrenia. These findings provide a theoretical basis from which the development of novel therapeutic strategies such as fatty acid and antioxidant supplementation can occur in the future. C1 VA Pittsburgh Healthcare Syst, Neurochem & Psychopharmacol Lab, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Robert Wood Johnson Pharmaceut Res Inst, Raritan, NJ USA. RP VA Pittsburgh Healthcare Syst, Neurochem & Psychopharmacol Lab, Bldg 13,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu FU NIMH NIH HHS [MH43742, MH44841, MH58141] NR 190 TC 204 Z9 211 U1 2 U2 7 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1172-7047 EI 1179-1934 J9 CNS DRUGS JI CNS Drugs PY 2001 VL 15 IS 4 BP 287 EP 310 DI 10.2165/00023210-200115040-00004 PG 24 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 423AZ UT WOS:000168154400004 PM 11463134 ER PT J AU Sonawalla, SB Fava, M AF Sonawalla, SB Fava, M TI Severe depression - Is there a best approach? SO CNS DRUGS LA English DT Review ID PITUITARY-ADRENAL-AXIS; TREATMENT-RESISTANT DEPRESSION; PHOTON-EMISSION TOMOGRAPHY; KILLER-CELL-ACTIVITY; CEREBRAL BLOOD-FLOW; MAJOR DEPRESSION; ELECTROCONVULSIVE-THERAPY; DOUBLE-BLIND; ANTIDEPRESSANT DRUGS; UNIPOLAR DEPRESSION AB A major depressive episode can be categorised as severe based on depressive symptoms, scores on depression rating scales, the need for hospitalisation, depressive subtypes, functional capacity, level of suicidality and the impact that the depression has on the patient. Several biological, psychological and social factors, and the presence of comorbid psychiatric or medical illnesses, impact on depression severity. A number of factors are reported to influence outcome in severe depression, including duration of illness before treatment, severity of the index episode, treatment modality used, and dosage and duration of and compliance with treatment. Potential complications of untreated severe depression include suicide, self-mutilation and refusal to eat, and treatment resistance. Several antidepressants have been studied in the treatment of severe depression. These include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline (norepinephrine) reuptake inhibitors, noradrenergic and specific serotonergic antidepressants, serotonin 5-HT2 receptor antagonists, monoamine oxidase inhibitors, and amfebutamone (bupropion). More recently, atypical antipsychotics have shown some utility in the management of severe and resistant depression. Data on the differential efficacy of TCAs versus SSRIs and the newer antidepressants in severe depression are mixed. Some studies have reported that TCAs are more efficacious than SSRIs; however, more recent studies have shown that TCAs and SSRIs have equivalent efficacy. There are reports that some of the newer antidepressants may be more effective than SSRIs in the treatment of severe depression, although the sample sizes in some of these studies were small. Combination therapy has been reported to be effective. The use of an SSRI-TCA combination, while somewhat controversial, may rapidly reduce depressive symptoms in some patients with severe depression. The combination of an antidepressant and an antipsychotic drug is promising and may be considered for severe depression with psychotic features. Although the role of cognitive behaviour therapy (CBT) in severe depression has not been adequately studied, a trial of CBT may be considered in severely depressed patients whose symptoms respond poorly to an adequate antidepressant trial, who are intolerant of antidepressants, have contraindications to pharmacotherapy, and who refuse medication or other somatic therapy. A combination of CBT and antidepressants may also be beneficial in some patients. Electroconvulsive therapy (ECT) may be indicated in severe psychotic depression, severe melancholic depression, resistant depression, and in patients intolerant of antidepressant medications and those with medical illnesses which contraindicate the use of antidepressants (e.g. renal, cardiac or hepatic disease). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02114 USA. RP Fava, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program,Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 105 TC 50 Z9 56 U1 4 U2 26 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2001 VL 15 IS 10 BP 765 EP 776 DI 10.2165/00023210-200115100-00003 PG 12 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 492RH UT WOS:000172181000003 PM 11602003 ER PT S AU Bizheva, K Boas, D AF Bizheva, K Boas, D BE Tuchin, VV Izatt, JA Fujimoto, JG TI Depth penetration limit to optical coherence microscopy in turbid media: the effect of multiply scattered light detection on image contrast and resolution SO COHERENCE DOMAIN OPTICAL METHODS IN BIOMEDICAL SCIENCE AND CLINICA APPLICATIONS V SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Coherence Domain Optical Methods in Biomedical Science and Clinical Applications V CY JAN 23-24, 2001 CL SAN JOSE, CA SP SPIE AB It is a well established fact that detection of multiply scattered light causes image quality degradation in optical microscopy. In this study experimental and computational methods were employed to examine the effect of multiply scattered light detection on the image contrast, resolution and image penetration depth of optical coherence microscopy (OCM) in turbid media. Dynamic low coherence interferometry (DLCI), a method sensitive to changes in the photon momentum transfer resulting from scattering, was used to study the OCM background light rejection ability in homogeneous turbid media and to determine the optical depths at which single scattered, multiply scattered and diffuse light constitute the dominant components of the measured intensity. OCM resolution measurements performed at various optical depths in scattering media revealed correlation between loss of OCM spatial resolution and spectrum linewidth broadening (DLCI) resulting from detection of multiply scattered light. The data from the resolution measurements was used to determine the dependence of image contrast, resolution and penetration depth on the optical properties of the turbid background and the instrument imaging geometry. In addition, a Monte Carlo model was designed to examine the contribution of background light (light that does not carry any information about the imaged object buried in a turbid medium) and multiply scattered signal light (light reflected off the object and multiply scattered while traversing the turbid layer above) to loss of OCM image quality. The results from this study contribute to our understanding of the practical limits to OCM imaging in turbid media. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3929-0 J9 PROC SPIE PY 2001 VL 4251 BP 1 EP 5 DI 10.1117/12.427871 PG 5 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BS45U UT WOS:000169895900001 ER PT B AU Petit, F Minns, AB Hettiaratchy, SP Mathes, DW Nazzal, JA Svennevik, ER Randolph, MA Lee, WPA AF Petit, F Minns, AB Hettiaratchy, SP Mathes, DW Nazzal, JA Svennevik, ER Randolph, MA Lee, WPA BE Dubernard, JM TI New trends and future direction of research in composite tissue allotransplantation SO COMPOSITE TISSUE ALLOGRAFTS LA English DT Proceedings Paper CT 3rd International Symposium on Composite Tissue Allografts CY NOV 29-30, 2001 CL LYON, FRANCE SP Merieux Fdn ID DONOR-SPECIFIC TOLERANCE; TRANSPLANTATION TOLERANCE; IMMUNOSUPPRESSIVE AGENTS; ALLOGRAFT TOLERANCE; TACROLIMUS FK506; MIXED CHIMERISM; SKIN ALLOGRAFT; BONE-MARROW; T-CELL; INDUCTION C1 Harvard Univ, Sch Med, Plast Surg Res Lab, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Petit, F (reprint author), Harvard Univ, Sch Med, Plast Surg Res Lab, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE BN 2-7420-0415-7 PY 2001 BP 9 EP 15 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA BU50M UT WOS:000176162300003 ER PT B AU Lee, WPA Mathes, DW Randolph, MA Butler, PEM AF Lee, WPA Mathes, DW Randolph, MA Butler, PEM BE Dubernard, JM TI Composite tissue allografts: perspectives from a laboratory SO COMPOSITE TISSUE ALLOGRAFTS LA English DT Proceedings Paper CT 3rd International Symposium on Composite Tissue Allografts CY NOV 29-30, 2001 CL LYON, FRANCE SP Merieux Fdn ID BONE-MARROW; IN-UTERO; TOLERANCE; TRANSPLANTATION; CYCLOSPORINE; SWINE; INDUCTION; SURVIVAL; MODEL; STRATEGIES C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, WAC-453,15 Parkman St, Boston, MA 02114 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE BN 2-7420-0415-7 PY 2001 BP 111 EP 115 PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA BU50M UT WOS:000176162300021 ER PT S AU Stankovic, KM AF Stankovic, KM BE Greenberg, S Slaney, M TI A method for evaluation of multiparameter nonlinear models illustrated on a computational model of auditory-nerve rate-level curves SO COMPUTATIONAL MODELS OF AUDITORY FUNCTION SE NATO SCIENCE SERIES, SERIES A: LIFE SCIENCE LA English DT Proceedings Paper CT Conference of the NATO Advanced-Study-Institute on Computational Hearing CY JUL 01-12, 1998 CL IL CIOCCO, ITALY SP NATO, USN, Off Res, USAF, Off Sci Res ID RATE-INTENSITY FUNCTIONS; BASILAR-MEMBRANE NONLINEARITY; FIBERS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Harvard Mit Div Hlth Sci & Technol, Sch Med,Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Stankovic, KM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Harvard Mit Div Hlth Sci & Technol, Sch Med,Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-6686 BN 90-5199-457-5 J9 NATO SCI S A LIF SCI PY 2001 VL 312 BP 17 EP 27 PG 11 WC Acoustics; Computer Science, Interdisciplinary Applications; Neurosciences; Otorhinolaryngology SC Acoustics; Computer Science; Neurosciences & Neurology; Otorhinolaryngology GA BT88W UT WOS:000174363200004 ER PT S AU Kalluri, S Delgutte, B AF Kalluri, S Delgutte, B BE Greenberg, S Slaney, M TI Characteristics of cochlear nucleus onset units studied with a model SO COMPUTATIONAL MODELS OF AUDITORY FUNCTION SE NATO SCIENCE SERIES, SERIES A: LIFE SCIENCE LA English DT Proceedings Paper CT Conference of the NATO Advanced-Study-Institute on Computational Hearing CY JUL 01-12, 1998 CL IL CIOCCO, ITALY SP NATO, USN, Off Res, USAF, Off Sci Res ID AUDITORY-NERVE FIBERS; OCTOPUS CELLS; BUSHY CELLS; HORSERADISH-PEROXIDASE; COMPUTATIONAL MODEL; RESPONSE PROPERTIES; NEURON TYPES; CAT; ENHANCEMENT; MECHANISMS C1 Massachusetts Eye & Ear Infirm, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02114 USA. RP Kalluri, S (reprint author), Massachusetts Eye & Ear Infirm, Harvard Mit Div Hlth Sci & Technol, 243 Charles St, Boston, MA 02114 USA. NR 48 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-6686 BN 90-5199-457-5 J9 NATO SCI S A LIF SCI PY 2001 VL 312 BP 29 EP 44 PG 16 WC Acoustics; Computer Science, Interdisciplinary Applications; Neurosciences; Otorhinolaryngology SC Acoustics; Computer Science; Neurosciences & Neurology; Otorhinolaryngology GA BT88W UT WOS:000174363200005 ER PT S AU Cariani, P AF Cariani, P BE Greenberg, S Slaney, M TI Neural timing nets for auditory computation SO COMPUTATIONAL MODELS OF AUDITORY FUNCTION SE NATO SCIENCE SERIES, SERIES A: LIFE SCIENCE LA English DT Proceedings Paper CT Conference of the NATO Advanced-Study-Institute on Computational Hearing CY JUL 01-12, 1998 CL IL CIOCCO, ITALY SP NATO, USN, Off Res, USAF, Off Sci Res ID COMPLEX TONES; INFERIOR COLLICULUS; PITCH; IDENTIFICATION; INFORMATION; PERCEPTION; RESPONSES; NEURONS; MEMORY; SYSTEM C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 59 TC 2 Z9 2 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-6686 BN 90-5199-457-5 J9 NATO SCI S A LIF SCI PY 2001 VL 312 BP 233 EP 247 PG 15 WC Acoustics; Computer Science, Interdisciplinary Applications; Neurosciences; Otorhinolaryngology SC Acoustics; Computer Science; Neurosciences & Neurology; Otorhinolaryngology GA BT88W UT WOS:000174363200023 ER PT J AU Yaghouti, F Nouri, M Abad, JC Power, WJ Doane, MG Dohlman, CH AF Yaghouti, F Nouri, M Abad, JC Power, WJ Doane, MG Dohlman, CH TI Keratoprosthesis: Preoperative prognostic categories SO CORNEA LA English DT Article DE keratoprosthesis; preoperative prognostics AB Purpose. Recent advances aimed at preventing and treating complications after keratoprosthesis surgery have improved prognosis, but it has been suspected that various preoperative diagnoses may carry substantially different postoperative outcomes. This article attempts to clarify the ranking of prognostic categories for patients undergoing keratoprosthesis surgery. Methods. A retrospective review of the outcome in a recent series of 63 patient eyes operated at the Massachusetts Eye and Ear Infirmary between 1990 and 1997 and followed up for a minimum of 21 months. Anatomic retention of the device and the loss of vision caused by complications were recorded. The patients were divided into four categories according to preoperative cause. Results. Anatomically, one keratoprosthesis extruded spontaneously. Another 10 were permanently removed because of complications. Of the 63 eyes, 10 never achieved a visual acuity of at least 20/200 vision because of preexisting retinal or optic nerve damage. The remaining 53 had a visual acuity of 20/200 to 20/20 as follows: Stevens-Johnson syndrome (n = 7), after 2 years: 33%, after 5 years: 0%; chemical burn (n = 17), after 2 years: 64%, after 5 years: 25%; ocular cicatricial pemphigoid (n = 20), after 2 years. 72%, after 5 years: 43%; graft failure in noncicatrizing conditions (dystrophies, degenerations, or bacterial or viral infections) when a repeat graft was expected to have a poor prognosis (n = 19), after 2 years: 83%, after 5 years: 68%. The difference in outcome between the Stevens-Johnson syndrome outcome group and the graft failure group or the ocular cicatricial pemphigoid group was statistically significant. In the group of 53 eyes, visual acuity was restored to 20/200 to 20/20 for a cumulative total of 138 years. Conclusion. Outcome of the keratoprosthesis surgery varied markedly with preoperative diagnosis. Most favorable was graft failures in noncicatrizing conditions, whereas Stevens-Johnson syndrome was the worst. Ocular cicatricial pemphigoid and chemical bums occupied a middle ground. The difference between the groups seemed to correlate with the degree of past preoperative inflammation. C1 Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dohlman, CH (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 141 Z9 147 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JAN PY 2001 VL 20 IS 1 BP 19 EP 23 DI 10.1097/00003226-200101000-00003 PG 5 WC Ophthalmology SC Ophthalmology GA 385YX UT WOS:000166033700003 PM 11188997 ER PT J AU Jain, S McCally, RL Connolly, PJ Azar, DT AF Jain, S McCally, RL Connolly, PJ Azar, DT TI Mitomycin C reduces corneal light scattering after excimer keratectomy SO CORNEA LA English DT Article DE corneal scar; excimer laser; keratectomy; mitomycin; rabbits; wound healing ID PHOTOREFRACTIVE KERATECTOMY; LASER KERATECTOMY; 193 NM; KERATOMILEUSIS; FIBROBLASTS; RABBITS; SUBCONJUNCTIVAL; 5-FLUOROURACIL; PTERYGIUM; ABLATION AB Purpose, To evaluate the effect of intraoperative mitomycin C (MMC) on corneal light scattering after excimer laser keratectomy. Methods, Phototherapeutic keratectomy (PTK) was performed in 24 rabbit eyes. After 40-mum epithelial ablation, animals were divided into three groups. In group 1, filter paper discs soaked with MMC (group 1A, 0.5 mg/mL; group 1B, 0.25 mg/ml) were applied for 1 minute. In group 2, annular filter papers soaked with MMC (group 2A, 0.5 mg/mL; group 2B, 0.25 mg/mL) were applied for I minute. Controls received vehicle only (group 3). Six-millimeter diameter 100-mum deep PTK was performed. Corneal light scattering was measured weekly from 1 to 6 weeks, at 10 weeks, and at 8 and 13 months using a scatterometer. A corneal light scattering index (SI) ranging from 0 to 10 was calculated; SI of 1 represents normal scattering. Results. A statistically significant decrease in mean SI was noted in group 2A (annular MMC 0.5 mg/mL; p < 0.05) as compared with the control group at 2 weeks. At 10 weeks, SI approached baseline levels in group 2 and the control group but showed significant increase in group 1 (MMC disc; p < 0.05). At 8 and 13 months, SI showed no statistical differences between groups. Conclusions. Controlled application of 0.5 mg/mL MMC in the corneal midperiphery transiently reduces corneal light scattering after excimer keratectomy in this rabbit model. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Corneal & Refract Surg Serv, Boston, MA 02114 USA. Johns Hopkins Univ, Wilmer Inst, Baltimore, MD USA. Johns Hopkins Univ, Appl Phys Lab, Laurel, MD USA. Indiana Sch Med, Indianapolis, IN USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Corneal & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. RI McCally, Russell/A-7785-2009 FU NEI NIH HHS [EY10101, EY12165, EY01019] NR 31 TC 33 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JAN PY 2001 VL 20 IS 1 BP 45 EP 49 DI 10.1097/00003226-200101000-00009 PG 5 WC Ophthalmology SC Ophthalmology GA 385YX UT WOS:000166033700009 PM 11189003 ER PT J AU Agus, MSD Agus, ZS AF Agus, MSD Agus, ZS TI Cardiovascular actions of magnesium SO CRITICAL CARE CLINICS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PIG VENTRICULAR MYOCYTES; CORONARY-HEART-DISEASE; SERUM MAGNESIUM; CARDIAC MYOCYTES; ATRIAL CELLS; K+ CURRENT; CONCENTRATION-DEPENDENCE; INTRACELLULAR MAGNESIUM; POTASSIUM CHANNEL AB Extracellular and intracellular magnesium modulates calcium and potassium channels in the cardiac myocyte. Changes in concentration ha iie marked effects upon the action potential duration and can have important consequences in magnesium depletion syndromes and during cardiac ischemia. A number of clinical studies have suggested that hypomagnesemia and magnesium depletion are associated with ventricular arrhythmias, possibly reflecting the effects of magnesium upon ion channels. C1 MassGen Hosp Children, Div Pediat Crit Care Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Endocrinol, Boston, MA USA. Univ Penn, Sch Med, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. RP Agus, MSD (reprint author), MassGen Hosp Children, Div Pediat Crit Care Med, 55 Fruit St,Ellison 317, Boston, MA 02114 USA. NR 60 TC 27 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD JAN PY 2001 VL 17 IS 1 BP 175 EP + DI 10.1016/S0749-0704(05)70158-5 PG 13 WC Critical Care Medicine SC General & Internal Medicine GA 401VE UT WOS:000166948300012 PM 11219228 ER PT J AU Yoganandan, N Pintar, FA Maltese, MR AF Yoganandan, N Pintar, FA Maltese, MR TI Biomechanics of abdominal injuries SO CRITICAL REVIEWS IN BIOMEDICAL ENGINEERING LA English DT Review ID ACUTE DIAPHRAGMATIC RUPTURE; BLUNT TRAUMA; SEAT BELTS; HEPATIC-TRAUMA; THORACIC INJURY; LATERAL IMPACT; FRONTAL IMPACT; LUMBAR SPINE; ORGAN INJURY; MANAGEMENT AB Although considerable efforts have been advanced to investigate the biomechanical aspects of abdominal injuries, reviews have been very limited. The purpose of this article is to present a comprehensive review of the topic. Traumatic abdominal injuries occur due to penetrating or blunt loading. However, the present review is focused on blunt trauma. Because of the complexity of the abdomen, biomechanically relevant anatomical characteristics of the various abdominal organs are presented. The proposed mechanism of injury for these organs and methods for abdominal injury quantification are described. This is followed by a detailed analysis of the biomechanical literature with particular emphasis on experiments aimed to duplicate real world injuries and attempt to quantify trauma in terms of parameters such as force, deflection, viscous criteria, pressure criteria, and correlation of these variables with the severity of abdominal injury. Experimental studies include tests using primates, pigs, rats, beagles, and human cadavers. The effects of velocity, compression, padding, and impactor characteristics on tolerance; effects of pressurization and postmortem characteristics on abdominal injury; deduction of abdominal response corridors; and force-deflection responses (of the different abdominal regions and organs) are discussed. Output of initial research is presented on the development of a device to record the biomechanical parameters in an anthropomorphic test dummy during impact. Based on these studies and the current need for abdominal protection, recommendations are given for further research. C1 Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. US Dept Vet Affairs, Med Res Ctr, Milwaukee, WI 53226 USA. RP Yoganandan, N (reprint author), Med Coll Wisconsin, Dept Neurosurg, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 223 TC 10 Z9 10 U1 1 U2 5 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 0278-940X J9 CRIT REV BIOMED ENG JI Crit. Rev. Biomed. Eng. PY 2001 VL 29 IS 2 BP 173 EP 246 PG 74 WC Engineering, Biomedical SC Engineering GA 442XV UT WOS:000169311000001 PM 11417756 ER PT J AU Taubman, MA Kawai, T AF Taubman, MA Kawai, T TI Involvement of T-lymphocytes in periodontal disease and indirect and indirect induction of bone resorption SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE periodontitis; cytokines; chemokines; chemokine receptors; Th1/Th2 lymphocytes; bone resorption ID OSTEOCLASTOGENESIS-INHIBITORY FACTOR; LOCALIZED JUVENILE PERIODONTITIS; HUMAN PERIPHERAL-BLOOD; INFLAMED HUMAN GINGIVA; NECROSIS-FACTOR-ALPHA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOKINE GENE-EXPRESSION; FORMATION IN-VITRO; DENDRITIC CELLS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS AB Periodontal disease is a peripheral infection involving species of Gram-negative organisms. T-lymphocytes can be found in the dense inflammatory infiltrate in this disease. CD4+ and CD8+ T-cells are present in periodontal lesions, as are memory/activated T-lymphocytes. in addition, Th1-and Th2-type T-lymphocytes and their associated cytokines with a subtle polarization toTh1 maybe present. Th1-type T-cells up-regulate the production of pro-inflammatory cytokines IL-1 and TNF-alpha, which can induce bone resorption indirectly by promoting differentiation of osteoclast precursors and subsequently by activating osteoclasts. Such osteoclast differentiation is dependent on stimulation of osteoprotegerin ligand (OPG-L) production by osteoblastic cells. By contrast, activated T-cells, by virtue of direct production and expression of OPG-L, can directly promote osteoclast differentiation. OPGL appears to be predominantly expressed on Th1-type cells. The direct and indirect T-cell involvement in periodontal bone resorption appears to be dependent on the degree of Th1-type T-cell recruitment into inflamed gingival tissues. This T-cell recruitment is regulated by adhesion molecules and chemokines/chemokine receptors. The adhesion molecules involved include alpha4 and alpha6 integrins, LFA-1, and ICAM-1. The Th1-type T-cells preferentially express CCR5 and CXCR3, which are found prominently in diseased gingivae. By contrast, little CCR4, expressed by Th2-type T-cells, can be detected. Also, the chemokine ligands RANTES, MIP 1-alpha (both CCR5), and IP-10 (CXCR3 ligand) were elevated in inflamed periodontal tissues. The T-cell features in diseased periodontal tissues can be compared with those in rheumatoid arthritis, wherein bone resorption often attributed to Th1-type T-cell involvement has also been demonstrated. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-03420] NR 124 TC 168 Z9 179 U1 0 U2 6 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 2001 VL 12 IS 2 BP 125 EP 135 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 556DB UT WOS:000175833100004 PM 11345523 ER PT J AU Esch, TR AF Esch, TR TI Pathogenetic factors in Sjogren's syndrome: Recent developments SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE Sjogren's syndrome; pathogenesis; autoimmunity; apoptosis ID LABIAL SALIVARY-GLANDS; LYMPHOCYTE INTEGRIN ALPHA(E)BETA(7); MUSCARINIC ACETYLCHOLINE-RECEPTORS; LIGAND E-CADHERIN; EPITHELIAL-CELLS; T-CELLS; CAUTIONARY NOTE; TUNEL ASSAY; SYNDROME SS; APOPTOSIS AB The study of pathogenetic factors in Sjogren's syndrome ISSI has been problematic, given the overall paucity of coherent data that integrate basic research with clinical findings. The presumed autoimmune nature of SS suggests T-cells, autoantibodies, and cytokines as possible immune factors in the initiation and progression of SS. Recent work on programmed cell death (apoptosis) in SS and its models suggests this as a fourth potential mechanism of disease. These four areas of SS research are reviewed with an emphasis on the most recent findings related to mechanisms of disease. New findings confirm the potential for antigen presentation to T-cells in the salivary glands, as well as involvement of other adhesion molecules with respect to T-cell functions. Restrictions on the receptor repertoires of infiltrating T-cells are discussed, as are new findings on antigenic specificities of these cells. New findings on the specificities of autoantibodies observed in SS are reviewed with an eye toward potential mechanisms for depression of exocrine secretory capacity. Stimulating new findings concerning cytokine production in salivary and lacrimal gland are noted. Particular points of interest with regard to apoptosis include the wide range of values obtained for apoptotic activity in SS and its models, and potential means of resolving discongruent results and the study of factors influencing apoptosis are discussed. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. RP Esch, TR (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-43297] NR 48 TC 8 Z9 10 U1 1 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 2001 VL 12 IS 3 BP 244 EP 251 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 556DC UT WOS:000175833200004 PM 11497375 ER PT J AU Waters, D Schwartz, GG Olsson, AG AF Waters, D Schwartz, GG Olsson, AG TI The Myocardial Ischemia Reduction with Acute Cholesterol Lowering (MIRACL) trial: a new frontier for statins? SO CURRENT CONTROLLED TRIALS IN CARDIOVASCULAR MEDICINE LA English DT Editorial Material DE atorvastatin; 3-hydroxy-3-methylglutaryl CoA reductase inhibitor; myocardial infarction; unstable angina ID DISEASE AB The Myocardial Ischemia Reduction with Acute Cholesterol Lowering (MIRACL) Trial tested the hypothesis that intensive lowering of cholesterol with atorvastatin (80 mg/day) initiated 24-96 h after an acute coronary syndrome would, over 4 months, reduce the incidence of the composite endpoint of death, nonfatal infarction, resuscitated cardiac arrest, and recurrent symptomatic myocardial ischemia with new objective symptoms requiring emergency rehospitalization. This primary composite endpoint was reduced from 17.4% to 14.8% (P = 0.048) among the 3086 patients enrolled. The results of MIRACL suggest that patients with acute coronary syndromes should begin to receive this treatment before leaving hospital, irrespective of baseline levels of low-density lipoprotein-cholesterol. C1 San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. Linkoping Univ Hosp, Dept Med Care, S-58185 Linkoping, Sweden. RP Waters, D (reprint author), San Francisco Gen Hosp, Div Cardiol, Room 5G1,1001 Potrero Ave, San Francisco, CA 94110 USA. NR 12 TC 17 Z9 17 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1468-6694 J9 CURR CONTR TRIALS C JI Curr. Control Trials Cardivasc. Med. PY 2001 VL 2 IS 3 BP 111 EP 114 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 523EN UT WOS:000173941200003 ER PT J AU D'Angio, CT Ambati, J Phelps, DL AF D'Angio, CT Ambati, J Phelps, DL TI Do urinary levels of vascular endothelial growth factor predict proliferative retinopathy? SO CURRENT EYE RESEARCH LA English DT Article DE diabetic retinopathy; retinal neovascularization; urine; vascular endothelial growth factor; VEGF ID DIABETIC-RETINOPATHY; PERMEABILITY FACTOR; ANGIOGENIC PEPTIDE; CANCER-PATIENTS; ELEVATED LEVELS; FACTOR VEGF; TUMOR; EXPRESSION AB Purpose. Vascular endothelial growth factor (VEGF) is elevated in the vitreous of patients with proliferative retinopathies (PR). Angiogenic factors like VEGF are elevated in the urine of subjects with cancers, including those distant from the genitourinary tract. We hypothesized that local increases in VEGF in the vitreous would be reflected in the urine of subjects with PR. Methods. Urine samples were collected from adults with absent, mild, or severe (requiring laser photocoagulation) PR. VEGF was measured by enzyme linked immunosorbent assay. Results. Of 42 subjects, 16 had no PR and 26 had PR (8 mild, 18 severe). Thirty subjects had diabetes mellitus; 24 of these had PR. Subjects with PR were older than controls. Subjects with PR tended to have higher urinary VEGF (median 123 pg/ml Cr, range 3-1738) than controls without PR (median 93 pg/ml Cr, range 2-200) (p = 0.08). None of 16 controls, but 11/15 subjects with PR had >200 mg VEGF/mg Cr (p = 0.003), yielding high specificity (100%), but poor sensitivity (42%) of elevated urinary VEGF for PR. Urinary VEGF was also modestly correlated with urinary protein excretion (r(2) = 0.23). Correction of VEGF values for urinary protein abrogated any correlation with PR. Conclusions. Urinary levels of VEGF are associated with PR, but this relationship may be caused by concurrent renal diseases that result in proteinuria and/or renal VEGF production. The insensitivity of the association may preclude its use in screening to avoid eye examinations. C1 Univ Rochester, Sch Med & Dent, Dept Pediat, Strong Childrens Res Ctr, Rochester, NY 14642 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP D'Angio, CT (reprint author), Univ Rochester, Sch Med & Dent, Dept Pediat, Strong Childrens Res Ctr, Box 651,601 Elmwood Ave, Rochester, NY 14642 USA. FU NCRR NIH HHS [5 M01 RR00044] NR 21 TC 6 Z9 6 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PY 2001 VL 22 IS 2 BP 90 EP 94 DI 10.1076/ceyr.22.2.90.5526 PG 5 WC Ophthalmology SC Ophthalmology GA 430GW UT WOS:000168567000003 PM 11402385 ER PT J AU Chauncey, TR AF Chauncey, TR TI Drug resistance mechanisms in acute leukemia SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MEDIATED MULTIDRUG-RESISTANCE; SOUTHWEST-ONCOLOGY-GROUP; P-GLYCOPROTEIN; TOPOISOMERASE-II; CELL-LINES; MDR1 GENE; EXPRESSION; PROTEIN AB Markers of anticancer drug resistance are predictive of treatment response and outcome in patients with acute myeloid leukemia. Immunologic detection of the drug efflux pumps, P-glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1), correlate with functional assays of drug resistance. These accumulation defects also appear operable in acute lymphoblastic leukemia. Many of the efflux pumps identified share significant structural homology with the large superfamily of ATP-binding cassette transporters. Other markers such as lung-resistance protein, bcl-2, and breast cancer-resistance protein, have been described in acute myeloid leukemia patients although their pathophysiology and clinical relevance are less clear and the methodology for their quantification are not well standardized. Preclinical studies have shown that small molecules capable of reversing efflux can restore drug sensitivity in resistant tumor models. Although initial clinical studies were limited by both potency and specificity of the reverser, later studies with more effective reversers have in many instances been limited by pharmacokinetic interactions exacerbating the clinical toxicities of chemotherapy. Although one large randomized study has demonstrated a proven survival advantage without increased toxicity using cyclosporine, the inconsistent results with other modulators raise doubt as to the utility and overall strategy of using drug efflux blockers in patients with established Pgp overexpression. Many of these patients have additional resistance mechanisms, and achieving meaningful clinical responses will likely require more complex clinical strategies. Preventing or delaying development of drug resistance in chemosensitive patients represents another therapeutic strategy to be tested. Curr Opin Oncol 2001, 13:21-26 (C) 2001 Lippincott Williams & Wilkins, Inc. C1 VA Puget Sound Hlth Care Syst, Marrow Transplant Unit S3MTU, Seattle, WA 98108 USA. RP Chauncey, TR (reprint author), VA Puget Sound Hlth Care Syst, Marrow Transplant Unit S3MTU, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 65 TC 36 Z9 41 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JAN PY 2001 VL 13 IS 1 BP 21 EP 26 DI 10.1097/00001622-200101000-00005 PG 6 WC Oncology SC Oncology GA 388DN UT WOS:000166162300005 PM 11148681 ER PT J AU Otto, MW Pollack, MH Maki, KM Gould, RA Worthington, JJ Smoller, JW Rosenbaum, JF AF Otto, MW Pollack, MH Maki, KM Gould, RA Worthington, JJ Smoller, JW Rosenbaum, JF TI Childhood history of anxiety disorders among adults with social phobia: Rates, correlates, and comparisons with patients with panic disorder SO DEPRESSION AND ANXIETY LA English DT Article DE social phobia; childhood anxiety disorder; panic disorder; separation anxiety disorder ID BEHAVIORAL-INHIBITION; PSYCHIATRIC-DISORDERS; CHILDREN; ADOLESCENTS; ASSOCIATION; COMORBIDITY; HYPOTHESIS; PARENTS; FAMILY; SAMPLE AB We examined the rates and correlates of a childhood history of anxiety disorders in 100 adults with a primary diagnosis of social phobia (social anxiety disorder). Adulthood and childhood disorders were assessed by experienced clinicians with structured clinical interviews. Rates of childhood anxiety disorders were evaluated to diagnostic comorbidity and a comparison group of patients with panic disorder. Onset of social phobia occurred before age 18 in 80% of the sample. Over half of the sample (54%) met criteria for one or more childhood anxiety disorders other than social phobia: 47% for overanxious disorder, 25% for avoidant disorder, 13% for separation anxiety disorder, and 1% for childhood agoraphobia. A history of childhood anxiety was associated with an early age of onset of social phobia, greater severity of fear and avoidance of social situations, greater fears of negative evaluation, and greater anxiety and depression morbidity. Rates of childhood social phobia, overanxious disorder, and avoidant disorder were significantly higher in patients with social phobia relative to our panic-disordered comparison group. We found approximately equal rates of a childhood history of separation anxiety disorder in patients with social phobia and panic disorder, providing fin-ther evidence against a unique relationship between separation anxiety disorder and panic disorder. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, WACC-815,15 Parkman St, Boston, MA 02114 USA. NR 33 TC 59 Z9 66 U1 2 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2001 VL 14 IS 4 BP 209 EP 213 DI 10.1002/da.1068 PG 5 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 504YB UT WOS:000172882800002 PM 11754127 ER PT J AU Shear, MK Vander Bilt, J Rucci, P Endicott, J Lydiard, B Otto, MW Pollack, MH Chandler, L Williams, J Ali, A Frank, DM AF Shear, MK Vander Bilt, J Rucci, P Endicott, J Lydiard, B Otto, MW Pollack, MH Chandler, L Williams, J Ali, A Frank, DM TI Reliability and validity of a Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) SO DEPRESSION AND ANXIETY LA English DT Article DE anxiety disorders; generalized anxiety disorders; assessment instrument; outcomes AB The Hamilton Anxiety Rating Scale, a widely used clinical interview, assessment tool, lacks instructions for administration and clear anchor points for. th assignment of severity, ratings. We developed a Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) and report on a study comparing this version to the traditional form of this scale. Experienced interviewers from three Anxiety Disorders research sites conducted videotaped interviews using both traditional and structured instruments in 89 participants. A subset of the tapes was co-rated by all raters. Participants completed self-report symptom questionnaires. We observed high inter-rater and test-retest reliability using both formats. The structured format produced similar but consistently higher (+ 4.2) scores. Correlation with a self-report measure of over-all anxiety was also high and virtually identical for the two versions. We conclude that in settings where extensive training is not practical, the structured scale is air acceptable alternative to the traditional Hamilton Anxiety instrument. C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Columbia Univ, New York, NY USA. Med Univ S Carolina, Charleston, SC 29425 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pfizer Inc, New York, NY USA. RP Shear, MK (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH-53817, MH30915] NR 6 TC 164 Z9 169 U1 3 U2 22 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2001 VL 13 IS 4 BP 166 EP 178 DI 10.1002/da.1033 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 442NB UT WOS:000169290900002 PM 11413563 ER PT J AU Safren, SA Lanka, GD Otto, MW Pollack, MH AF Safren, SA Lanka, GD Otto, MW Pollack, MH TI Prevalence of childhood ADHD among patients with Generalized Anxiety Disorder and a comparison condition, Social Phobia SO DEPRESSION AND ANXIETY LA English DT Article DE attention-deficit hyperactivity disorder generalized anxiety disorder; social phobia; childhood history ID DEFICIT HYPERACTIVITY DISORDER; ADULTS; CHILDREN; SAMPLE C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 815,15 Parkman St, Boston, MA 02115 USA. NR 18 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2001 VL 13 IS 4 BP 190 EP 191 DI 10.1002/da.1036 PG 2 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 442NB UT WOS:000169290900005 PM 11413566 ER PT J AU Lupu, F Terwilliger, JD Lee, K Segre, GV Efstratiadis, A AF Lupu, F Terwilliger, JD Lee, K Segre, GV Efstratiadis, A TI Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth SO DEVELOPMENTAL BIOLOGY LA English DT Review DE growth; growth rate; growth retardation; growth hormone; growth hormone receptor; insulin-like growth factor 1; ossification; chondrocyte ID I IGF-I; LONGITUDINAL BONE-GROWTH; SNELL DWARF MICE; MESSENGER-RIBONUCLEIC-ACID; STRAINS CPB-S; GENE-EXPRESSION; BINDING PROTEIN; TRANSGENIC MICE; CELL-KINETICS; PLATE CHONDROCYTES AB To examine the relationship between growth hormone (GH) and insulin-like growth factor 1 (IGF1) in controlling postnatal growth, we performed a comparative analysis of dwarfing phenotypes manifested in mouse mutants lacking GH receptor, IGF1, or both. This genetic study has provided conclusive evidence demonstrating that GH and IGF1 promote postnatal growth by both independent and common functions, as the growth retardation of double Ghr/Igf1 nullizygotes is more severe than that observed with either class of single mutant. In fact, the body weight of these double-mutant mice is only similar to 17% of normal and, in absolute magnitude (similar to5 g), only twice that of the smallest known mammal. Thus, the growth control pathway in which the components of the GH/IGF1 signaling systems participate constitutes the major determinant of body size. To complement this conclusion mainly based on extensive growth curve analyses, we also present details concerning the involvement of the GH/IGF1 axis in linear growth derived by a developmental study of long bone ossification in the mutants. (C) 2001 Academic Press. C1 Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. Columbia Univ, Dept Psychiat, New York, NY 10032 USA. Columbia Univ, Genome Ctr, New York, NY 10032 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Efstratiadis, A (reprint author), Columbia Univ, Dept Genet & Dev, Russ Berrie Med Sci Pavil,1150 St Nicholas Ave, New York, NY 10032 USA. EM arg@cuccfa.ccc.columbia.edu FU NICHD NIH HHS [HD34526]; NIMH NIH HHS [MH50733] NR 128 TC 420 Z9 451 U1 3 U2 32 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 JAN 1 PY 2001 VL 229 IS 1 BP 141 EP 162 DI 10.1006/dbio.2000.9975 PG 22 WC Developmental Biology SC Developmental Biology GA 390ZK UT WOS:000166329500011 PM 11133160 ER PT J AU Zhang, J Rosenthal, A de Sauvage, FJ Shivdasani, RA AF Zhang, J Rosenthal, A de Sauvage, FJ Shivdasani, RA TI Downregulation of hedgehog signaling is required for organogenesis of the small intestine in Xenopus SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Hedgehog; intestine development; organogenesis; Smoothened; SmoM2; gut endoderm ID BASAL-CELL CARCINOMA; DROSOPHILA PATCHED GENE; SONIC-HEDGEHOG; HUMAN HOMOLOG; PANCREAS DEVELOPMENT; TRANSDUCING HEDGEHOG; MEMBRANE-PROTEIN; GERM LAYERS; MUTATIONS; MOUSE AB Hedgehog ligands interact with receptor complexes containing Patched (PTC) and Smoothened (SMO) proteins to regulate many aspects of development. The mutation W535L (SmoM2) in human Smo is associated with basal cell skin cancers, causes constitutive, ligand-independent signaling through the Hedgehog pathway, and provides a powerful means to test effects of unregulated Hedgehog signaling. Expression of SmoM2 in Xenopus embryos leads to developmental anomalies that are consistent with known requirements for regulated Hedgehog signaling in the eye and pancreas. Additionally, it results in failure of midgut epithelial cytodifferentiation and of the intestine to lengthen and coil. The midgut mesenchyme shows increased cell numbers and attenuated expression of the differentiation marker smooth muscle actin. With the exception of the pancreas, differentiation of foregut and hindgut derivatives is unaffected. The intestinal epithelial abnormalities are reproduced in embryos or organ explants treated directly with active recombinant hedgehog protein. Ptc mRNA, a principal target of Hedgehog signaling, is maximally expressed at stages corresponding to the onset of the intestinal defects. In advanced embryos expressing SmoM2, Ptc expression is remarkably confined to the intestinal wall. Considered together, these findings suggest that the splanchnic mesoderm responds to endodermal Hedgehog signals by inhibiting the transition of midgut endoderm into intestinal epithelium and that attenuation of this feedback is required for normal development of the vertebrate intestine. (C) 2001 Academic Press. C1 Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zhang, J (reprint author), Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA. NR 69 TC 34 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC 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 JAN 1 PY 2001 VL 229 IS 1 BP 188 EP 202 DI 10.1006/dbio.2000.9953 PG 15 WC Developmental Biology SC Developmental Biology GA 390ZK UT WOS:000166329500014 PM 11133163 ER PT J AU Dominov, JA Houlihan-Kamamoto, CA Swap, CJ Miller, JB AF Dominov, JA Houlihan-Kamamoto, CA Swap, CJ Miller, JB TI Pro- and anti-apoptotic members of the Bcl-2 family in skeletal muscle: A distinct role for Bcl-2 in later stages of myogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE apoptosis; Bcl-2 family; myoblast; Sca-1; skeletal muscle; myogenesis ID DYSTROPHIN-DEFICIENT MUSCLE; HEAVY-CHAIN ISOFORMS; CELL-DEATH; MUSCULAR-DYSTROPHY; POLYCYSTIC KIDNEY; MOUSE MUSCLE; MDX MOUSE; EXPRESSION; MICE; DIFFERENTIATION AB Apoptotic myonuclei appear during myogenesis and in diseased muscles. To investigate cell death regulation in skeletal muscle, we examined how members of the Bcl-2 family of apoptosis regulators are expressed and function in the C2C12 muscle cell. line and in primary muscle cells at different stages of development. Both anti-apoptotic (Bcl-W, Bcl-X-L) and pro-apoptotic (Bad, Bak, Bax) members of the Bcl-2 family were expressed in developing skeletal muscle in vivo. Each was also expressed in embryonic (E11-12), fetal (E15-16), and neonatal muscle stem cells, myoblasts, and myotubes in vitro. In contrast, Bcl-2 expression was Limited to a small group of mononucleate, desmin-positive, myogenin-negative muscle cells that were seen in fetal and neonatal, but not embryonic, muscle cell cultures. The cell surface protein Sca-1, which is associated with muscle and blood stem cells, was found on similar to1/2 of these Bcl-2-positive cells. Loss of Bcl-2 did not affect expression of other family members, because neonatal muscles of wild-type and Bcl-2-null mice had similar amounts of Bcl-X-L, Bcl-W, Bad, Bak, and Bax mRNAs. Loss of Bcl-2 did have functional consequences; however, because neonatal muscles of Bcl-2-null mice had only similar to2/3 as many fast muscle fibers as muscles in wild-type mice. Thus, Bcl-2 function is required for particular stages of fetal and postnatal myogenesis. (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Myogenesis Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Miller, JB (reprint author), Massachusetts Gen Hosp, Myogenesis Res Lab, 149 13th St,Room 6627, Charlestown, MA 02129 USA. NR 48 TC 29 Z9 29 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JAN PY 2001 VL 220 IS 1 BP 18 EP 26 DI 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1088>3.0.CO;2-# PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 385MN UT WOS:000166008400002 PM 11146504 ER PT J AU Bektas, A Hughes, JN Warram, JH Krolewski, AS Doria, A AF Bektas, A Hughes, JN Warram, JH Krolewski, AS Doria, A TI Type 2 diabetes locus on 12q15 - Further mapping and mutation screening of two candidate genes SO DIABETES LA English DT Article; Proceedings Paper CT 60th Scientific Sessions of the American-Diabetes-Association CY JUN 09-13, 2000 CL SAN ANTONIO, TEXAS SP Amer Diabet Assoc ID CARBOXYPEPTIDASE-E; MOLECULAR-CLONING; LINKAGE ANALYSIS; CHROMOSOME 12Q; YOUNG; GENOME; MICE; MAP AB We recently reported evidence of a novel type 2 diabetes locus placed on chromosome 12q15 between markers D12S375 and D12S1684 (Diabetes 48:2246-2251, 1999). Four multigenerational families having logarithm of odds (LOD) scores >1.0 in the original analysis were genotyped for 11 additional markers in this interval to refine this mapping; this allowed us to narrow the linked region to the interval between markers D12S1693 and D12S326. In a multipoint parametric analysis using the VITESSE software, the LOD score for linkage at this location reached 3.1 in one of these families. This interval contains the gene for protein tyrosine phosphatase receptor type R (PTPRR)-a protein that may be involved in both insulin secretion and action. After determining PTPRR exon-intron structure, we identified several polymorphisms in this gene but no mutation segregating with diabetes. The search for mutations was also negative for carboxypeptidase M (CPM)-another candidate gene mapped to this region. In summary, our data provide further evidence for the existence of a type 2 diabetes locus on chromosome 12q15. This locus, however, does not appear to correspond to the PTPRR or CPM, although a contribution of mutations in regulatory regions cannot be excluded at this time. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div,Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Doria, A (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div,Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-36836, DK-47475, DK-55523] NR 20 TC 19 Z9 22 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2001 VL 50 IS 1 BP 204 EP 208 DI 10.2337/diabetes.50.1.204 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 386XZ UT WOS:000166092000029 PM 11147789 ER PT J AU Liao, D Shofer, JB Boyko, EJ McNeely, MJ Leonetti, DL Kahn, SE Fujimoto, WY AF Liao, D Shofer, JB Boyko, EJ McNeely, MJ Leonetti, DL Kahn, SE Fujimoto, WY TI Abnormal glucose tolerance and increased risk for cardiovascular disease in Japanese-Americans with normal fasting glucose SO DIABETES CARE LA English DT Article ID WORLD-HEALTH-ORGANIZATION; DIABETES-ASSOCIATION CRITERIA; CORONARY HEART-DISEASE; DIAGNOSTIC-CRITERIA; PLASMA-GLUCOSE; FAT DISTRIBUTION; C-PEPTIDE; MEN; MELLITUS; 2ND-GENERATION AB OBJECTIVE - To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS - Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels, systolic and diastolic blood pressures (BPs); BMI (kg/m(2)); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria a's having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT). RESULTS - Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT. The mean values for NGT, IGT, and DGT, respectively and analysis of covariance P values, adjusted for age and sex, are as follows: intraabdominal fat area by CT 69.7, 95.0, and 101.1 cm(2) (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm(2) (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01). CONCLUSIONS - NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles. C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. Vet Affairs Epidemiol Res & Informat Ctr, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Liao, D (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Hlth Sci Bldg,Room 545,1959 NE Pacific, Seattle, WA 98195 USA. OI Kahn, Steven/0000-0001-7307-9002 FU NHLBI NIH HHS [HL-07028-25, HL-49293]; NIDDK NIH HHS [DK-31170] NR 28 TC 37 Z9 39 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2001 VL 24 IS 1 BP 39 EP 44 DI 10.2337/diacare.24.1.39 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 386XX UT WOS:000166091600009 PM 11194238 ER PT J AU Hayashi, T Ishida, T Motoya, S Itoh, F Takahashi, T Hinoda, Y Imai, K AF Hayashi, T Ishida, T Motoya, S Itoh, F Takahashi, T Hinoda, Y Imai, K TI Mucins and immune reactions to mucins in ulcerative colitis SO DIGESTION LA English DT Article; Proceedings Paper CT 5th Eisai Biwako Symposium on Intestinal Mucosal Damage and Repair CY NOV 19-20, 1999 CL LAKE BIWA, JAPAN DE MUC1; MUC2; goblet cell; sulphation; antibody-dependent cell-mediated cytotoxicity cytotoxic T lymphocytes ID INFLAMMATORY BOWEL-DISEASE; CORE PROTEIN; MUC1 MUCIN; CELLS; ANTIBODY; CANCER; CYTOTOXICITY; EXPRESSION; SULFATION; EPITOPE AB Ulcerative colitis (UC) is an inflammatory bower disease of undetermined etiology. Mucins, mainly produced by goblet cells, protect colon cells from various kinds of stress. Alteration in the quality or quantity of mucins may be the cause of the disease. Another possible cause is immune reactions to co ion ic cells. Anti-MUC1 antibodies were detected in the sera of patients with UC. Antibodies would destroy the colonic cells through antibody-dependent cell-mediated cytotoxicity. We reviewed the significance of mucins as well as humoral and cellular immunity in the pathogenesis of UC. Copyright (C) 2001 S. Karger AG, Basel. C1 Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. Yamaguchi Univ, Sch Med, Dept Clin Lab Sci, Ube, Yamaguchi 755, Japan. RP Hayashi, T (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 27 TC 16 Z9 16 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 J9 DIGESTION JI Digestion PY 2001 VL 63 SU 1 BP 28 EP 31 DI 10.1159/000051907 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 397TG UT WOS:000166711900007 PM 11173906 ER PT J AU Hayashi, T Takahashi, T Motoya, S Ishida, T Itoh, F Adachi, M Hinoda, Y Imai, K AF Hayashi, T Takahashi, T Motoya, S Ishida, T Itoh, F Adachi, M Hinoda, Y Imai, K TI MUC1 mucin core protein binds to the domain 1 of ICAM-1 SO DIGESTION LA English DT Article; Proceedings Paper CT 5th Eisai Biwako Symposium on Intestinal Mucosal Damage and Repair CY NOV 19-20, 1999 CL LAKE BIWA, JAPAN DE MUC1; ICAM-1 (intercellular adhesion molecule 1) metastasis; aggregation ID INTERCELLULAR-ADHESION MOLECULE-1; EPITHELIAL MUCIN; BREAST-CANCER; EXPRESSION; CELLS; GLYCOSYLATION; PROGRESSION; INHIBITION; ANTIGEN; CLONING AB Background: MUC1 is aberrantly expressed on a variety of epithelial tumors, We have reported that MUC1 plays important roles in separation from primary site, invasion into the stromal tissue, and protection from immune responses. The aim of this study is to determine the precise binding of MUC1 to intercellular adhesion molecule 1 (ICAM-1) that accelerates the cancer metastasis. Methods: A cell aggregation assay between MUC1 cDNA transfectants and ICAM-1 expressing cells was employed. An anti-MUC1 antibody, anti-ICAM-1 antibody or synthetic peptide of MUC1 core protein was added to the assay to inhibit the cell aggregation. Results: MUC1: transfectants showed a significantly higher aggregation rate compared to the control cells. Th is aggregation was further enhanced by the inhibition of O-glycan biosynthesis. It was inhibited by either an anti-MUC1 antibody recognizing the tandem repeat domain of MUC1 core protein or an anti-ICAM-1 antibody identifying domain 1. It was also inhibited by a synthetic MUC1 peptide of 40 amino acids corresponding to two tandem repeats. Conclusions: The results revealed that a tandem repeat domain of MUC1 mucin core protein binds to domain 1 of ICAM-1, suggesting a potential role of MUC1-ICAM-1 interaction in the metastasis of epithelial tumors. Copyright (C) 2001 S. Karger AG, Basel. C1 Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. Yamaguchi Univ, Sch Med, Dept Clin Lab Sci, Ube, Yamaguchi 755, Japan. RP Hayashi, T (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM Toshiaki_Hayashi@dfci-harvard.edu NR 22 TC 32 Z9 36 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 EI 1421-9867 J9 DIGESTION JI Digestion PY 2001 VL 63 SU 1 BP 87 EP 92 DI 10.1159/000051917 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 397TG UT WOS:000166711900017 PM 11173916 ER PT J AU Bonds, DE Freedberg, KA AF Bonds, DE Freedberg, KA TI Combining utility measurements - Exploring different approaches SO DISEASE MANAGEMENT & HEALTH OUTCOMES LA English DT Article ID POSTPARTUM THYROID-DYSFUNCTION; DEPENDENT DIABETES-MELLITUS; COST-EFFECTIVENESS; HEALTH STATES; PREFERENCES; DEPRESSION; PREVALENCE; STRATEGIES; ANTIBODIES; DIAGNOSIS AB Background: The use of utility values in cost-effectiveness analysis is an accepted method for defining outcomes. Increasingly, cost-effectiveness analyses examine outcomes that involve two or more health states. There is no accepted method of mathematically combining single health state,utility values into a surrogate value that represents the combined health state. Objective: To test the effect of different mathematical approaches to combining single health state utility values into a surrogate value on the cost-effectiveness ratio, in a sample model. Methods: We employed a realistic decision analysis model to test the cost-effectiveness of screening for postpartum thyroiditis. Utility values for type I diabetes mellitus and thyroiditis were taken from the literature and combined using different methods. Results: The surrogate utility values obtained using the multiplicative method were higher than those obtained with the additive method (for example, the state of both type I diabetes mellitus and treated thyroiditis had a value of 0.75 for the multiplicative method versus 0.73 for the additive method). The resulting cost-effectiveness ratios for the screening strategy were slightly higher, $US16 000 (1998 values) per quality-adjusted life-year (QALY), for the multiplicative method when compared to the additive method ($US14 000 per QALY). This small difference was consistently maintained during sensitivity analyses. Conclusion: All methods of combining utilities resulted in similar values. Until a consensus is reached on the method of choice, researchers should consider using both methods in sensitivity analyses and reporting both sets of results. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gen Internal Med, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Massachusetts Gen Hosp, Harvard Sch Publ Hlth, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Div Gen Internal Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Partners AIDS Res Ctr, Boston, MA USA. RP Bonds, DE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gen Internal Med, Bowman Gray Campus,Med Ctr Blvd, Winston Salem, NC 27157 USA. NR 40 TC 4 Z9 4 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-8790 J9 DIS MANAG HEALTH OUT JI Dis. Manag. Health Outcomes PY 2001 VL 9 IS 9 BP 507 EP 516 DI 10.2165/00115677-200109090-00005 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 482RQ UT WOS:000171589400005 ER PT J AU Elman, I D'Ambra, MN Krause, S Breiter, H Kane, M Morris, R Tuffy, L Gastfriend, DR AF Elman, I D'Ambra, MN Krause, S Breiter, H Kane, M Morris, R Tuffy, L Gastfriend, DR TI Ultrarapid opioid detoxification: effects on cardiopulmonary physiology, stress hormones and clinical outcomes SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 12-17, 1999 CL ACAPULCO, MEXICO SP Coll Problems Drug Dependence DE anesthesia; naltrexone; ACTH; cortisol; craving; withdrawal ID RAPID OPIATE DETOXIFICATION; PITUITARY-ADRENAL AXIS; GENERAL-ANESTHESIA; HEROIN-ADDICTS; NALTREXONE; NALOXONE; ACTIVATION; WITHDRAWAL; EFFICACY; DEPENDENCE AB This study explored the acute and long-term consequences of ultrarapid opioid detoxification (URD) in individuals with opioid dependence. In an open case series, seven patients underwent URD and subsequent treatment with daily naltrexone. Structured interviews, integrated rehabilitation and hair sampling were employed in the 12-week course of longitudinal follow-up. Cardiac and pulmonary physiology did not change significantly during the anesthesia phase of URD, but plasma ACTH and cortisol levels increased 15- and 13-fold, respectively. Marked withdrawal and tachypnea in all patients and respiratory distress in one patient occurred during the acute post-anesthesia phase. Withdrawal scores were significantly elevated for 3 weeks compared with baseline in the face of minimal self-reported craving for opioids. Anxiety, depression and vegetative symptoms improved gradually. Four patients remained abstinent of opioid use, two reported a brief period of opioid intake and one relapsed into daily opioid consumption. Given its effect on breathing and stress hormones, this procedure should be conducted by experienced anesthesiologists. The fact that URD and subsequent naltrexone treatment appears to cause a dissociation effect in the usual relationship between withdrawal and craving has implications for behavioral pharmacology. Further research is needed on the efficacy, safety, mechanisms and neurobiological sequelae of the procedure. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Addict Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol,Cardiac Anesthesia Grp, Boston, MA 02114 USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Addict Serv, 15 Parkman St,WACC-812, Boston, MA 02114 USA. FU NCRR NIH HHS [M01 RR01066]; NIDA NIH HHS [DA 08781] NR 42 TC 17 Z9 19 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2001 VL 61 IS 2 BP 163 EP 172 DI 10.1016/S0376-8716(00)00139-3 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 389ER UT WOS:000166226100008 PM 11137281 ER PT J AU Cornish, JW Maany, I Fudala, PJ Ehrman, RN Robbins, SJ O'Brien, CP AF Cornish, JW Maany, I Fudala, PJ Ehrman, RN Robbins, SJ O'Brien, CP TI A randomized, double-blind, placebo-controlled study of ritanserin pharmacotherapy for cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE pharmacotherapy; ritanserin; cocaine dependence; serotonin antagonist; treament ID FAILURE; HUMANS; BLOCK; ABUSE; SLEEP; RATS AB Eighty cocaine-dependent individuals enrolled in outpatient treatment took part in a randomized, double-blind, placebo-controlled trial of ritanserin, a 5-HT2 antagonist, as an adjunct therapy. Participants attended an outpatient day hospital therapy program each day and received tablets containing placebo or 10 mg ritanserin for a 4-week period. Primary outcome measures included retention in treatment, urine drug tests, and self-reports of craving. Secondary outcome measures were depression scores on the Beck and Hamilton inventories, negative mood as measured by the Profile of Mood States, and life functioning as measured by the Addiction Severity Index. Although participants showed improvement over the 4 weeks, there were no group differences on any of the measures. These results fail to support the use of ritanserin as a complement to outpatient psychosocial therapy for cocaine dependence. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Beaver Coll, Glenside, PA 19038 USA. RP Cornish, JW (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [P50-DA09252-02] NR 24 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2001 VL 61 IS 2 BP 183 EP 189 DI 10.1016/S0376-8716(00)00140-X PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 389ER UT WOS:000166226100010 PM 11137283 ER PT J AU Ongini, E Monopoli, A Impagnatiello, F Fredduzzi, S Schwarzschild, M Chen, JF AF Ongini, E Monopoli, A Impagnatiello, F Fredduzzi, S Schwarzschild, M Chen, JF TI Dual actions of A(2A) adenosine receptor antagonists on motor dysfunction and neurodegenerative processes SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT PURINES 2000 Meeting CY JUL 09-13, 2000 CL MADRID, SPAIN SP PURINES DE adenosine; A(2A) adenosine receptors; A(2A) adenosine receptor antagonists; A(2A) knockout mice; Parkinson's disease; Huntington's disease; neuroprotection ID CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; MICE LACKING; RAT; EXPRESSION; MPTP; PROTECTION; DISORDERS; AGONISTS; ISCHEMIA AB Of the four known adenosine receptors, the A(2A) receptor has received much attention over the last few years. The discovery of high-affinity and selective A(2A) adenosine receptor antagonists, together with the development of different genetic lines of mice lacking A(2A) receptors, have greatly contributed to the new insights into the mechanisms whereby A(2A) receptors modulate central nervous system functions. Efforts made using the prototypic A(2A) receptor antagonists, e.g., the 8-styrylxanthine KW 6002 and the pyrazolotriazolopyrimidine SCH 58261, have shown that these drugs are effective in different models of motor impairment mimicking the main features of Parkinson's disease. Moreover, these drugs show neuroprotective properties in models of brain injury. Consistent with pharmacology, A(2A) receptor knockout mice have been found to be less sensitive to both motor impairment and neurochemical changes relevant to neurodegenerative disorders. The main effect of A(2A) receptor blockade or inactivation is related to selective interaction with dopamine-mediated function in the striatum. However, there are responses which appear to be independent of dopamine receptors while the mechanisms underlying neuroprotection remain to be elucidated. Overall, there are now compounds that appear to be promising for treatment of Parkinson's disease and related neurodegenerative disorders. The efforts currently ongoing to understand their efficacy in patients will make it possible to assess whether A(2A) receptor blockers are a new interesting class of antiparkinsonian agents. Drug Dev. Res. 52:379-386, 2001. (C) 2001 Wiley-Liss, Inc. C1 Schering Plough Res Inst, I-20132 Milan, Italy. Massachusetts Gen Hosp, Charlestown, MA USA. RP Monopoli, A (reprint author), Schering Plough Res Inst, San Raffaele Sci Pk,Via Olgettina 58, I-20132 Milan, Italy. NR 53 TC 9 Z9 9 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JAN-FEB PY 2001 VL 52 IS 1-2 BP 379 EP 386 DI 10.1002/ddr.1137 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 429TE UT WOS:000168532400046 ER PT J AU Solai, LKK Mulsant, BH Pollock, BG AF Solai, LKK Mulsant, BH Pollock, BG TI Selective serotonin reuptake inhibitors for late-life depression - A comparative review SO DRUGS & AGING LA English DT Review ID NURSING-HOME RESIDENTS; HUMAN LIVER-MICROSOMES; COMPLICATING ALZHEIMERS-DISEASE; TRIAL COMPARING SERTRALINE; MULTICENTER DOUBLE-BLIND; MAJOR DEPRESSION; IN-VITRO; CLINICAL-TRIAL; GERIATRIC-PATIENTS; POTENT INHIBITOR AB Late-life depression is a serious health problem that is challenging to manage but generally responds well to pharmacotherapy. Selective serotonin (5-hydroxy-tryptamine; 5-HT) reuptake inhibitors (SSRIs), the most commonly prescribed antidepressants. are usually used as first-line agents for elderly patients with depression. Like most drugs, SSRIs have not been widely tested in clinical trials that approximate 'real-life' geriatric situations. However. studies completed to dare provide valuable information about the efficacy, safety and tolerability of this class of antidepressants among older patients with depression, including those with depression secondary to stroke or dementia and those with other comorbid physical disorders. Although one SSRI may be more efficacious or better tolerated by elderly patients than another. existing data do not support such claims. However. other distinguishing features may influence the choice of agent. For example, fluoxetine, fluvoxamine and paroxetine are more likely to be involved in significant drug-drug interactions than are citalopram or sertraline. In contrast to the other SSRIs, fluoxetine has a half-life well in excess of 1 day, which can be an advantage when weaning the patient off therapy in that it may reduce the incidence of discontinuation symptoms, but a significant disadvantage if the patient cannot tolerate the drug or experiences an adverse drug-drug interaction. C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Univ Pittsburgh Med Ctr, Geriatr Psychopharmacol Program, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Solai, LKK (reprint author), UPMC, Beaver Valley Mental Hlth Serv, 176 Virginia Ave, Rochester, PA 15074 USA. FU NIMH NIH HHS [MH 01613, MH 52247, MH 59666, MH 01509] NR 75 TC 45 Z9 48 U1 3 U2 8 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2001 VL 18 IS 5 BP 355 EP 368 DI 10.2165/00002512-200118050-00006 PG 14 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 435EF UT WOS:000168863900006 PM 11392444 ER PT J AU Anand, BS AF Anand, BS TI Drug treatment of the complications of cirrhosis in the older adult SO DRUGS & AGING LA English DT Article ID SPONTANEOUS BACTERIAL PERITONITIS; HEPATORENAL-SYNDROME; ANTIBIOTIC-PROPHYLAXIS; PREDICTIVE FACTORS; HEPATIC-ENCEPHALOPATHY; RENAL IMPAIRMENT; CONTROLLED TRIAL; LIVER-DISEASE; DOUBLE-BLIND; ASCITES AB Several age-related changes occur in the structure and functions of the liver. The volume of the liver decreases, despite an increase in the size of hepatocytes, suggesting loss of liver cells. There are decreases in hepatic blood flow, the synthesis of urea and cholesterol, and the metabolism of drugs. Moreover, the regenerative capacity of liver becomes less efficient. Certain caveats are important when treating older patients with liver disease. Strict dietary restrictions, such as a low protein diet, should be avoided in the elderly (unless the patient is encephalopathic) because these patients are often undernourished to start with. Similarly, strict salt restriction should be enforced with caution, since it makes food less palatable and may take away what little desire such patients have to eat. Diuretic doses should be adjusted carefully because of greater risks of azotaemia and electrolyte disturbances in the elderly. Extra vigilance should be exercised in the early detection of infections that are more likely to occur in patients with cirrhosis. For example, spontaneous bacterial peritonitis can be mussed in the elderly because of poor systemic (fever, abdominal tenderness) and laboratory responses (leucocytosis). In patients presenting with acute variceal bleeding. it is better to err on the side of underhydration than overhydration because of the risk of congestive heart failure. Vasopressin should be avoided in the elderly, since this drug has a high probability of precipitating an ischaemic event. Older patients do not tolerate beta -blockers as well as younger individuals and may require other treatment strategies for the prevention of variceal rebleeding episodes. Hepatic encephalopathy, especially the milder form, needs careful assessment because it can be easily confused with senile dementia syndromes. Cirrhosis is a premalignant condition and patients are at increased risk of developing hepatocellular carcinoma (HCC), a tumour seen predominantly in the elderly. All patients with cirrhosis should be maintained on a lifelong screening programme consisting of a 6-monthly assessment of alpha -fetoprotein and an imaging study, since early detection provides the only hope for cure of HCC. The only definitive treatment of cirrhosis is liver transplantation. Advanced age is not a contraindication to transplantation, and survival in older patients (aged > 60 years) is comparable to that in younger individuals. C1 Baylor Coll Med, Houston, TX 77030 USA. RP Anand, BS (reprint author), VA Med Ctr, Digest Dis Sect 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 53 TC 5 Z9 5 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2001 VL 18 IS 8 BP 575 EP 585 DI 10.2165/00002512-200118080-00002 PG 11 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 468UG UT WOS:000170776100002 PM 11587244 ER PT J AU Le, DA Lipton, SA AF Le, DA Lipton, SA TI Potential and current use of N-methyl-D-aspartate (NMDA) receptor antagonists in diseases of aging SO DRUGS & AGING LA English DT Article ID CHANNEL BLOCKER MEMANTINE; LONG-TERM POTENTIATION; EXCITATORY AMINO-ACIDS; CENTRAL-NERVOUS-SYSTEM; ACUTE ISCHEMIC STROKE; NITRIC-OXIDE; MEDIATED NEUROTOXICITY; GLUTAMATE NEUROTOXICITY; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE AB The N-methyl-D-aspartate (NMDA) receptor complex is a subtype of glutamate receptor and its dysfunction is involved in many neurological disorders associated with aging, including chronic pain, depression, stroke and Parkinson's disease. Multiple clinical trials using NMDA receptor antagonists have been aborted mainly due to the severe psychomimetic adverse effects of these drugs that occur before concentrations can reach an adequate level in the brain. In this review, we present the evidence that clinically safer NMDA antagonists such as memantine and nitroglycerin., and the combination drug nitro-memantine, are promising as drugs in treating neurodegenerative diseases. C1 Burnham Inst, Ctr Neurosci & Aging, La Jolla, CA 92037 USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Stroke & Neurovasc Regulat Lab, Boston, MA USA. RP Lipton, SA (reprint author), Burnham Inst, Ctr Neurosci & Aging, La Jolla, CA 92037 USA. FU NEI NIH HHS [R01 EY05477, R01 EY09024]; NICHD NIH HHS [P01 HD29587]; NIMH NIH HHS [R01 MH58164] NR 72 TC 52 Z9 56 U1 0 U2 7 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2001 VL 18 IS 10 BP 717 EP 724 DI 10.2165/00002512-200118100-00001 PG 8 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 498EU UT WOS:000172497500001 PM 11735619 ER PT J AU Foster, GP Picard, MH AF Foster, GP Picard, MH TI Intracardiac echocardiography: Current uses and future directions SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE intracardiac; echocardiography ID REGURGITANT ORIFICE AREA; INTRACORONARY ULTRASOUND IMAGES; IN-VITRO VALIDATION; AORTIC-VALVE AREA; INTRAVASCULAR ULTRASOUND; VIVO; INSUFFICIENCY; CATHETER; STENOSIS; MICE AB Advances in transducer technology have enabled development of catheter-based ultrasound imaging devices that produce very high resolution images of vessels and cardiac structures. Although the majority of clinical use has been in, the evaluation of the coronary and peripheral vasculature, a broad spectrum of cardiac applications continue to develop, including evaluations of the ventricles, valves, and great vessels, as well as the guidance of electrophysiological procedures. Specifically, introduction of the ultrasound catheter into the heart results in dynamic, real-time images for assessment and quantitation of ventricular systolic function, severity of valve stenosis, and extent of regurgitant orifices. The intracardiac applications have the potential to become the gold standard for quantitation of valve dynamics and a critical tool in the ICU for prolonged monitoring of cardiac physiology. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab VBK508, Div Cardiol, Boston, MA 02114 USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab VBK508, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 30 TC 10 Z9 10 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JAN PY 2001 VL 18 IS 1 BP 43 EP 48 DI 10.1046/j.1540-8175.2001.00043.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 404FN UT WOS:000167086900009 PM 11182782 ER PT J AU Moritz, W Leech, CA Ferrer, J Habener, JF AF Moritz, W Leech, CA Ferrer, J Habener, JF TI Regulated expression of adenosine triphosphate-sensitive potassium channel subunits in pancreatic beta-cells SO ENDOCRINOLOGY LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; K-ATP CHANNEL; AFFINITY SULFONYLUREA RECEPTOR; BINDING-PROTEIN-BETA; INSULIN-SECRETION; HIGH GLUCOSE; GENE-TRANSCRIPTION; MEXICAN-AMERICANS; DIABETES-MELLITUS; SEQUENCE VARIANTS AB The regulation of glucose-dependent insulin secretion in pancreatic beta -cells is linked to the expression and function of the ATP-sensitive potassium channel (K-ATP), which is composed of a sulfonylurea receptor (SUR1) and an inwardly rectifying potassium channel (Kir6.2). Previous animal and human genetic studies have demonstrated that disruption or defective expression of K-ATP subunit genes has a profound impact on the regulation of insulin secretion. Little is known about how SUR1 and Kir6.2 gene expression is regulated. Here we show that high glucose concentrations lead to a marked decrease (similar to 70%) in Kir6.2 messenger RNA (mRNA) levels in isolated rat pancreatic islets as well as in the INS-1 beta -cell line. This effect is reversible, because exposure to low glucose reinduces Kir6.2 transcript levels. The cognate K-ATP, channel subunit SUR1 showed similar downregulation at high glucose concentration. The K-ATP channel activity of INS-1 cells cultivated at high glucose was reduced by 33-51%. In contrast, glucagon-like peptide-1 (GLP-1) induced Kir6.2 mRNA steady state levels and was able to prevent glucose-dependent inhibition of Kir6.2 mRNA and K-ATP channel activity. To provide further insight into the mechanisms by which glucose and GLP-1 regulate beta -cell KATP channel genes, we have cloned and initiated the characterization of the Kir6.2 gene transcriptional regulatory regions contained within the entire 4,5 kb flanked by the SUR1 and Kir6.2 genes. Transient transfection experiments with five deletion constructs in a pancreatic beta -cell line (INS-1) showed that the proximal 988 bp of the Kir6.2 promoter sequence contributes only 25-30% to the total basal promoter activity. The minimal promoter region -67/+140, also encompassing parts of the 5'-untranslated region, confers sensitivity to GLP-1, which stimulates transcriptional activity of the Kir6.2 minigene by about 2-fold. We propose that glucose- and GLP-1-dependent regulation of K-ATP subunit genes may be important in the adaptation of beta -cells to changes in secretory demands in physiological and diseased states. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, 55 Fruit St,WEL320, Boston, MA 02114 USA. RI Ferrer, Jorge/A-3176-2012 NR 47 TC 33 Z9 39 U1 0 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2001 VL 142 IS 1 BP 129 EP 138 DI 10.1210/en.142.1.129 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390QW UT WOS:000166308700017 PM 11145575 ER PT J AU Cousin, SP Hugl, SR Wrede, CE Kajio, H Myers, MG Rhodes, CJ AF Cousin, SP Hugl, SR Wrede, CE Kajio, H Myers, MG Rhodes, CJ TI Free fatty acid-induced inhibition of glucose and insulin-like growth factor I-induced deoxyribonucleic acid synthesis in the pancreatic beta-cell line INS-1 SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; SKELETAL-MUSCLE CELLS; SIGNAL-TRANSDUCTION; DIABETES-MELLITUS; IGF-I; ZETA; ACTIVATION; RESISTANCE; STIMULATION; APOPTOSIS AB Pancreatic beta -cell mitogenesis is increased by insulin-like growth factor I(IGF-I) in a glucose-dependent manner. In this study it was found that alternative beta -cell nutrient fuels to glucose, pyruvate, and glutamine/leucine independently induced and provided a platform for IGF-I to induce INS-1 cell DNA synthesis in the absence of serum. In contrast, long chain FFA (greater than or equal toC(12)) inhibited 15 mM glucose-induced [H-3]thymidine incorporation (+/-10 nM IGF-I) by 95% or more within 24 h above 0.2 mM FFA complexed to 1% BSA (K-0.5 for palnitate/1% BSA = 65-85 muM for 24 h; t(0.5) for 0.2 mM palmitate/1% BSA = similar to6 h). FFA-mediated inhibition of glucose/IGF-I-induced beta -cell DNA synthesis was reversible, and FFA oxidation did not appear to he required, nor did FFA interfere with glucose metabolism in INS-1 cells. An examination of mitogenic signal transduction pathways in INS-1 cells revealed that glucose/IGF-I induction of early signaling elements in SH2-containing protein (Shc)- and insulin receptor substrate-1/2-mediated pathways leading to downstream mitogen-activated protein kinase and phosphoinositol 3'-kinase activation, were unaffected by FFA. However, glucose-/IGF-I-induced activation of protein kinase B (PKB) was significantly inhibited, and protein kinase C-zeta was chronically activated by FFA. It is possible that FFA-mediated inhibition of beta -cell mitogenesis contributes to the reduction of beta -cell mass and the subsequent failure to compensate for peripheral insulin resistance in vivo that is key to the pathogenesis of obesity-linked diabetes. C1 Pacific NW Res Inst, Seattle, WA 98122 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98122 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Rhodes, CJ (reprint author), Pacific NW Res Inst, 720 Broadway, Seattle, WA 98122 USA. NR 53 TC 127 Z9 137 U1 0 U2 10 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2001 VL 142 IS 1 BP 229 EP 240 DI 10.1210/en.142.1.229 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390QW UT WOS:000166308700028 PM 11145586 ER PT J AU Arai, M Assil, IQ Abou-Samra, AB AF Arai, M Assil, IQ Abou-Samra, AB TI Characterization of three corticotropin-releasing factor receptors in catfish: A novel third receptor is predominantly expressed in pituitary and urophysis SO ENDOCRINOLOGY LA English DT Article ID IMPAIRED STRESS-RESPONSE; CENTRAL-NERVOUS-SYSTEM; AMINO-ACID-SEQUENCE; UROTENSIN-I; MESSENGER-RNA; IMMUNOHISTOCHEMICAL LOCALIZATION; CATOSTOMUS-COMMERSONI; PARATHYROID-HORMONE; XENOPUS-LAEVIS; RAINBOW-TROUT AB The present study reports the isolation of three complementary DNA (cDNA) clones encoding distinct subtypes of CRF receptors from the diploid catfish (cf) species, Ameiurus nebulosus. The first clone encodes a 446-amino acid protein (cfCRF-R1) that is highly homologous to mouse (m) CRF-R1 (93% identical). The cfCRF-R1 messenger RNA is highly expressed in the brain, and its distribution pattern correlates well with that of mammalian CRF-R1, except for weak expression in the pituitary. When transiently expressed in COS-7 cells, cfCRF-R1 bound CRF, urotensin I, and sauvagine with similar affinities. The second full-length cDNA, which was cloned from catfish heart, encodes a 406-amino acid protein that showed homology to murine CRF-R2 (88%) and when expressed in COS-7 cells preferentially bound sauvagine. The highest level of cfCRF-R2 expression was observed in the heart. The third full-length cDNA clone, which encodes a 428-amino acid protein, is structurally closer to cfCRF-R1 (85%) than to cfCRF-R2 (80%). This novel CRF receptor (cfCRF-R3) bound CRF with a 5-fold higher affinity than urotensin I and sauvagine and was expressed in the pituitary gland, urophysis, and brain. The presence of three different CRF receptors, each with distinct tissue distribution and ligand binding properties, suggests a complex CRF/urotensin I system. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abou-Samra, AB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 50 TC 102 Z9 106 U1 2 U2 6 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2001 VL 142 IS 1 BP 446 EP 454 DI 10.1210/en.142.1.446 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390QW UT WOS:000166308700051 PM 11145609 ER PT J AU Whitsel, EA Raghunathan, TE Pearce, RM Lin, D Rautaharju, PM Lemaitre, R Siscovick, DS AF Whitsel, EA Raghunathan, TE Pearce, RM Lin, D Rautaharju, PM Lemaitre, R Siscovick, DS TI RR interval variation, the QT interval index and risk of primary cardiac arrest among patients without clinically recognized heart disease SO EUROPEAN HEART JOURNAL LA English DT Article DE autonomic function; cardiac arrest; electrocardiography; risk factors ID AUTONOMIC NERVOUS-SYSTEM; RATE-VARIABILITY; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; MORTALITY; ELECTROCARDIOGRAPHY; PROLONGATION; ABNORMALITIES; PROPRANOLOL; CRITERIA AB Aims Autonomic tone influences RR interval variation (RRV) and the heart rate-corrected QT interval index (QTI). Together, QTI and RRV may improve characterization of sympathovagal control and estimation of risk of primary cardiac arrest. We therefore examined effects of QTI and short-term RRV from standard, 12-lead electrocardiograms on risk of primary cardiac arrest among persons without clinically recognized heart disease. Methods and Results We analysed data from a case-control study of risk factors for primary cardiac arrest among enrollees in a large health plan. Cases (n=505) were enrollees aged 18 to 79 years without history of heart disease who had primary cardiac arrest between 1980 and 1994. Controls (n=529) were a demographically similar, stratified random sample of enrollees. We determined enrollee characteristics from ambulatory medical records, QTI and RRV from standard, 12-lead electrocardiograms, and medication use from automated pharmacy files. Low and high Values of QTI and RRV were designated as the first and fifth quintiles of QTI (96% and 107%) and RRV (35 ms and 120 ms) among controls. In a model adjusting for clinical predictors of primary cardiac arrest, RRV modified the association between QTI and risk of primary cardiac arrest (P=0(.)05). Compared to high RRV and low QTI, the risk of primary cardiac arrest (odds ratio [95% CI]) was 0(.)95 [0(.)73-1(.)23] at low RRV and QTI, 1(.)23 [0(.)97-1(.)57] at high RRV and QTI, and 1(.)55 [1(.)16-2(.)06] at low RRV and high QTI. Risk remained elevated after adjustment for other electrocardiographic predictors and medication use. Conclusion Autonomic dysfunction, characterized by high QTI and low RRV on the standard, 12-lead electrocardiogram, is associated with an increased risk of primary cardiac arrest among persons without clinically recognized heart disease. (C) 2001 The European Society of Cardiology. C1 Cardiovasc Hlth Res Unit, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Field Program, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Epidemiol Cardiol Res Ctr, Winston Salem, NC 27103 USA. RP Whitsel, EA (reprint author), Univ N Carolina, Dept Epidemiol, Cardiovasc Dis Program, Bank Amer Ctr, Suite 306,137 E Franklin St, Chapel Hill, NC 27514 USA. FU NHLBI NIH HHS [HL-42456-03] NR 40 TC 33 Z9 33 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2001 VL 22 IS 2 BP 165 EP 173 DI 10.1053/euhj.2262.2175 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 392BB UT WOS:000166389800010 PM 11161918 ER PT J AU Vogel, C Cobleigh, MA Tripathy, D Gutheil, JC Harris, LN Fehrenbacher, L Slamon, DJ Murphy, M Novotny, WF Burchmore, M Shak, S Stewart, SJ AF Vogel, C Cobleigh, MA Tripathy, D Gutheil, JC Harris, LN Fehrenbacher, L Slamon, DJ Murphy, M Novotny, WF Burchmore, M Shak, S Stewart, SJ CA Genentech H0650 Study Investigators TI First-line, single-agent Herceptin (R) (trastuzumab) in metastatic breast cancer: a preliminary report SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Herceptin (R) (trastuzumab); metastatic breast cancer; first-line; clinical trial; efficacy ID ANTI-HER2 MONOCLONAL-ANTIBODY; PHASE-II; CHEMOTHERAPY; XENOGRAFTS; RECEPTOR; THERAPY AB Following confirmation of the appropriate dosage, safety and potential efficacy of Herceptin(R) (trastuzumab) in small-scale phase I and II trials involving patients with refractory disease, a large trial was conducted in 222 patients with breast cancer who had relapsed after one or two chemotherapy regimens for their metastatic disease. The results showed a positive and durable overall response rate (15% according to a response evaluation committee (REC) assessment) using trastuzumab monotherapy (initial dose 4 mg/kg intravenously (i.v.) followed by 2 mg/kg i.v. weekly). In another recently completed phase II trial, 113 patients were randomised to two dose levels (initial dose of 4 mg/kg i.v, dose followed by 2 mg/kg i.v, weekly, or initial dose of 8 mg/kg followed by 4 mg/kg i.v. weekly) of single-agent trastuzumab as first-line therapy for metastatic disease. The preliminary overall response rate was 4 23% based on investigator assessment, and tolerability was excellent as in previous trials; efficacy was similar in both dose groups, but the side-effects tended to be more frequent in the higher dose group, The preferred dosage is therefore the same as that currently recommended, i.e. an initial dose of 4 mg/kg i.v. followed by 2 mg/kg weekly i.v. until disease progression, (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Miami, Sch Med, Miami, FL USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94120 USA. Vical Inc, San Diego, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Kaiser Permanente, Vallejo, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Genentech Inc, S San Francisco, CA 94080 USA. RP Vogel, C (reprint author), Univ Miami, Sch Med, Miami, FL USA. NR 14 TC 59 Z9 59 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2001 VL 37 SU 1 BP S25 EP S29 PG 5 WC Oncology SC Oncology GA 408PL UT WOS:000167334500005 PM 11167088 ER PT J AU Mangoni, AA DiSalvo, TG Vlahakes, GJ Polanczyk, CA Fifer, MA AF Mangoni, AA DiSalvo, TG Vlahakes, GJ Polanczyk, CA Fifer, MA TI Outcome following isolated tricuspid valve replacement SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE heart valve surgery; tricuspid regurgitation; tricuspid stenosis; tricuspid valve ID HANCOCK PORCINE BIOPROSTHESIS; POSITION; SURGERY; EXPERIENCE; PROSTHESIS AB Objectives: The clinical outcome of isolated tricuspid valve replacement is not well defined because this procedure is usually performed concomitantly with other valve surgery, Methods: We retrospectively studied the short and long-term outcome of 15 consecutive patients (six men and nine women, aged 61 +/- 3 years) undergoing isolated tricuspid valve replacement from 1984 to 1996. The cause of valve dysfunction was rheumatic heart disease in 12 patients, healed endocarditis in two patients, and sarcoidosis in one patient. The tricuspid valve was stenotic in one patient, regurgitant in eight patients, and both stenotic and regurgitant in six patients. A St. Jude Medical prosthesis was placed in eight patients, Carpentier-Edwards in five patients, and Bjork-Shiley and Starr-Edwards in one patient each. Results: The median survival was only 1.2 years. Three patients (20%) died less than or equal to 30 days after the surgery or before discharge, and six other patients (40%) died within 3 years of surgery. Anasarca was the only predictor of short-term mortality (P = 0.03), while the predictors of long-term mortality were anemia (P = 0.01), rheumatic heart disease (P = 0.03), previous stroke (P = 0.01), and previous mitral valve surgery (P = 0.03). Conclusions: Isolated tricuspid valve replacement is characterized by a poor short and long-term outcome. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Div, Boston, MA 02114 USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RI Mangoni, Arduino/F-8000-2010; Polanczyk, Carisi/D-6208-2013 NR 18 TC 32 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD JAN PY 2001 VL 19 IS 1 BP 68 EP 73 DI 10.1016/S1010-7940(00)00598-4 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 402FR UT WOS:000166975800017 PM 11163563 ER PT J AU Battle, TE Roberson, MS Zhang, T Varvayanis, S Yen, A AF Battle, TE Roberson, MS Zhang, T Varvayanis, S Yen, A TI Retinoic acid-induced blr1 expression requires RAR alpha, RXR, and MAPK activation and uses ERK2 but not JNK/SAPK to accelerate cell differentiation SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE BLR1; retinoids; leukemic monocytic cell differentiation; MAPK ID PROTEIN-COUPLED RECEPTOR; ACUTE PROMYELOCYTIC LEUKEMIA; RESPONSIVE ELEMENT; ALL-TRANS; MYELOID DIFFERENTIATION; BETA-GENE; B-CELLS; INDUCTION; CHEMOKINE; PROMOTER AB Upstream signaling requirements of retinoic acid (RA)induced blr1 expression and downstream signaling consequences of blr1 over-expression in a human myeloid leukemia cell line demonstrate that mitogen-activated protein kinase (MAPK) signaling complexes are involved in both avenues. RA-induced myeloid differentiation and G(1)/G(0) growth arrest of HL-60 cells is known to require the activation of the RAR alpha and RXR retinoid receptors, as well as activation of the MAPK, ERK2. Transcriptional activation of the Burkitt's lymphoma receptor 1 (blr1) gene occurs early during RA-induced differentiation of HL-60 cells and requires these same three activating processes. The use of retinoid ligands that activate either the RAR alpha or the RXR retinoid receptors revealed that blr1 mRNA induction was detectable only when both RAR alpha and RXR were activated. Neither the RAR alpha nor RXR selective ligands alone induced expression of blr1, but the combination of the two ligands induced the expression of blr1 to the same extent as RA. The MAPKK (MEK) inhibitor, PD98059, was used to determine whether extracellular signal-regulated kinase (ERK2) activation was necessary for induction of blr1 mRNA, PD98059 inhibited induced blr1 mRNA expression, due to RA or activated RAR alpha plus RXR ligands, indicating that ERK2 activation is necessary for blr1 mRNA expression. Previous studies showed that ectopic expression of blr1 also caused increased MAPK activation, in particular ERK2, and subsequently accelerated RA-induced differentiation and G(1)/G(0) growth arrest. Inhibition of ERK2 activation inhibited differentiation of blr1 transfectants, suggesting that the accelerated differentiation reflected blr1-enhanced ERK2 activation. The present data also demonstrate that ectopic expression of blr1 increased JNK/SAPK activity, but JNK/SAPK activation was not needed for accelerated RA-induced differentiation and growth arrest. The results show that the signals known to be required for HL-60 differentiation, activated RAR alpha, RXR, and ERK2, are necessary for blr1 mRNA expression. Downstream consequences of blr1 overexpression include enhanced MAPK signaling. C1 Cornell Univ, Coll Vet Med, Dept Biomed Sci, Sect Pathol, Ithaca, NY 14853 USA. Cornell Univ, Coll Vet Med, Dept Biomed Sci, Physiol Sect, Ithaca, NY 14853 USA. RP Battle, TE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Mayer 549,44 Binney St, Boston, MA 02115 USA. RI Varvayanis, Susi/F-1945-2010 FU NIEHS NIH HHS [ESO7052] NR 36 TC 29 Z9 31 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JAN PY 2001 VL 80 IS 1 BP 59 EP 67 DI 10.1078/0171-9335-00141 PG 9 WC Cell Biology SC Cell Biology GA 399UU UT WOS:000166831600007 PM 11211936 ER PT J AU Wang, RJ Ramaswamy, S Hu, D Cantor, H AF Wang, RJ Ramaswamy, S Hu, D Cantor, H TI Definition of a novel binding site on CD8 cells for a conserved region of the MHC class 1b molecule Qa-1 that regulates IFN-gamma expression SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD8; Qa-1; IFN-gamma; MHC; T cell development ID T-CELLS; LYMPHOCYTES; CD94/NKG2A; RECEPTORS; ANTIGEN AB Natural killer (NK) cells and activated CD8 cells both express cytotoxic activity and produce substantial levels of IFN-gamma in response to viral and bacterial infections. In the case of NK cells, cellular activation and IFN-gamma expression are regulated by an interaction between NK receptors and MHC class Ib molecules, including HLA-E/Qa-1. We have used soluble tetrameric complexes of the murine class Ib molecule Qa-1 to define the significance of this interaction for CD8 cells. We find that all CD8 cells express a receptor for Qa-1 and that ligation of this receptor by Qa-1 results in up-regulation of IFN-gamma production. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Cantor, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, SM 722,44 Binney St, Boston, MA 02115 USA. RI Hu, Dan/D-9642-2015 FU NHLBI NIH HHS [T32 HL07623]; NIAID NIH HHS [AI13600, AI 37562] NR 14 TC 12 Z9 12 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2001 VL 31 IS 1 BP 87 EP 93 DI 10.1002/1521-4141(200101)31:1<87::AID-IMMU87>3.0.CO;2-3 PG 7 WC Immunology SC Immunology GA 393UH UT WOS:000166487700011 PM 11169442 ER PT J AU Azuara, V Grigoriadou, K Lembezat, MP Nagler-Anderson, C Pereira, P AF Azuara, V Grigoriadou, K Lembezat, MP Nagler-Anderson, C Pereira, P TI Strain-specific TCR repertoire selection of IL-4-producing Thy-1(dull) gamma delta thymocytes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE gamma delta T lymphocyte; T cell development; thymus; cytokine ID CELL RECEPTOR-ALPHA/BETA(+) CELLS; RECEPTOR-ALPHA-CHAIN; T-CELLS; CD8 THYMOCYTES; GENE FAMILIES; PRODUCE IL-4; BONE-MARROW; MICE; SUBSET; DIVERSE AB Thy-1(dull) gamma delta thymocytes constitute an unusual subset of mature TCR gamma delta cells which share with NK T cells the expression of cell surface markers usually associated with activated or memory cells and the simultaneous production of high levels of IL-4 and IFN-gamma upon activation. In DBA/2 mice, Thy-1(dull) gamma delta thymocytes express a restricted repertoire of TCR that are composed of the V gamma1 gene product mainly associated with V delta6.4 chains exhibiting very limited junctional sequence diversity. In this study we have characterized this gamma delta T cell population in different strains of mice and show that Thy-1(dull) gamma delta thymocytes are present in every strain tested, albeit at different frequencies. Moreover IL-4 production by gamma delta thymocytes is mainly confined to the Thy-1(dull) gamma delta population in every strain tested. Finally, the repertoire of TCR expressed by Thy-1(dull) gamma delta thymocytes varies in different strain of mice, although a biased expression of V gamma1 and V delta6 chains was observed in all strains studied. However, the extent of junctional diversity of the V gamma1 and V delta6 chains expressed by Thy-1(dull) gamma delta thymocytes varied from oligoclonal in DBA/2 mice to polyclonal in FVB/N mice. Thy-1(dull) gamma delta thymocytes from mouse strains such as C3H/HeJ and BALB/c contain cells with diverse V delta6(D)J delta junctions together with cells with relatively homogeneous V delta6(D)J delta junctions, similar to those found in DBA/2. Thus, the Thy-1(dull) gamma delta population appears to contain two subsets of cells which differ in the diversity of their TCR. C1 Inst Pasteur, CNRS, URA 1961, Unite Dev Lymphocytes, F-75724 Paris 15, France. Massachusetts Gen Hosp, Mucosal Immun Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Pereira, P (reprint author), Inst Pasteur, CNRS, URA 1961, Unite Dev Lymphocytes, 25 Rue Dr Roux, F-75724 Paris 15, France. RI Pereira, Pablo/M-7224-2014; OI Azuara, Veronique/0000-0003-4608-3713 NR 44 TC 18 Z9 20 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2001 VL 31 IS 1 BP 205 EP 214 DI 10.1002/1521-4141(200101)31:1<205::AID-IMMU205>3.0.CO;2-8 PG 10 WC Immunology SC Immunology GA 393UH UT WOS:000166487700023 PM 11265636 ER PT J AU Rao, VLR Dogan, A Bowen, KK Todd, KG Dempsey, RJ AF Rao, VLR Dogan, A Bowen, KK Todd, KG Dempsey, RJ TI Antisense knockdown of the glial glutamate transporter GLT-1 exacerbates hippocampal neuronal damage following traumatic injury to rat brain SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE antisense ODN; controlled cortical impact injury; glutamate uptake; hippocampus; knockdown; neuronal death ID CONTROLLED CORTICAL IMPACT; OXIDE SYNTHASE EXPRESSION; IN-VIVO; EXTRACELLULAR GLUTAMATE; CELL-DEATH; ISCHEMIA; RELEASE; INHIBITION; SUBTYPE; EXCITOTOXICITY AB Traumatic injury to rat brain induced by controlled cortical impact (CCI) results in chronic neuronal death in the hippocampus. In the normal brain, glutamate transporters actively clear the glutamate released synaptically to prevent receptor overactivation and excitotoxicity. Glutamate transporter 1 (GLT-1) is the most abundant and active glutamate transporter, which mediates the bulk of glutamate uptake. CCI injury significantly decreased GLT-1 mRNA (by 49-66%, P < 0.05) and protein (by 29-44%, P < 0.05) levels in the ipsilateral hippocampus, compared with either the respective contralateral hippocampus or the sham-operated control, 24-72 h after the injury, CCI injury in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) exacerbated the hippocampal neuronal death and mortality, compared with the GLT-1 sense/random ODN-infused controls. At 7 days after the injury, hippocampal neuronal numbers were significantly lower in the CAI (reduced by 32%, P < 0.05), CA2 (by 45%, P < 0.01), CA3 (by 68%, P < 0.01) and dentate gyrus (by 31%, P < 0.05) in GLT-1 antisense ODN-infused rats, compared with the GLT-1 sense/random ODN-infused controls. This study suggested a role for GLT-1 dysfunction in promoting the hippocampal neuronal death after traumatic brain injury. C1 Univ Wisconsin, Dept Neurol Surg, Madison, WI 53706 USA. Univ Wisconsin, Cardiovasc Res Ctr, Madison, WI USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. Univ Alberta, Dept Psychiat, Edmonton, AB, Canada. RP Rao, VLR (reprint author), Univ Wisconsin, Dept Neurol Surg, Madison, WI 53706 USA. FU NINDS NIH HHS [NS28000, NS31220] NR 63 TC 58 Z9 63 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2001 VL 13 IS 1 BP 119 EP 128 DI 10.1046/j.1460-9568.2001.01367.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 394KJ UT WOS:000166523000012 PM 11135010 ER PT J AU Hogemann, D Flemming, P Kreipe, H Galanski, M AF Hogemann, D Flemming, P Kreipe, H Galanski, M TI Correlation of MRI and CT findings with histopathology in hepatic angiomyolipoma SO EUROPEAN RADIOLOGY LA English DT Article DE hepatic angiomyolipoma; intralesional fat; immunohistochemical staining ID TUBEROUS SCLEROSIS; HEPATOCELLULAR-CARCINOMA; LIVER; BENIGN; DIFFERENTIATION; DIAGNOSIS; VARIANTS; PATIENT; LESIONS; TUMORS AB Hepatic angiomyolipomas are rare and often mimic other liver tumors. The aim of our study was to describe the CT and MRI findings and to correlate imaging features with histopathology. The CT and/or MR images were available for retrospective analysis in seven patients. Patients had non-enhanced as well as enhanced CT (n = 6) or MRI (n = 4) before and after administration of Gd-DTPA (n = 2) or MnDPDP, a liver specific contrast agent, (n = 3). In three patients CT and MRI did not detect fat, and in two patients the angiomyolipomas were also histopathologically devoid of fat. Vascularity ranged from hypervascular (n = 4) with arteriovenous shunts (n = 1) to equal (n = 1) or less (n = 2) postcontrast enhancement compared with the normal liver parenchyma. No uptake of the liver specific contrast agent, MnDPDP, was observed (n = 3). Predominantly, CT and MRI did not include angiomyolipoma in the differential diagnosis, and the initial histopathological evaluation was inconclusive in more than half the cases. Hepatic angiomyolipomas frequently manifest as solitary well-circumscribed heterogeneous masses in patients with no underlying liver disease or elevation of serum tumor markers. If present, the demonstration of intratumoral fat is helpful in the diagnosis of angiomyolipoma. The final diagnosis can be obtained by immunohistochemistry. C1 Hannover Med Sch, Inst Pathol, D-30625 Hannover, Germany. Hannover Med Sch, Dept Radiol, D-30625 Hannover, Germany. RP Hogemann, D (reprint author), Massachusetts Gen Hosp, CMIR Radiol, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 33 TC 35 Z9 42 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PY 2001 VL 11 IS 8 BP 1389 EP 1395 DI 10.1007/s003300000750 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 460YJ UT WOS:000170337800012 PM 11519547 ER PT J AU Wunderbaldinger, P Bremer, C Matuszewski, L Marten, K Turetschek, K Rand, T AF Wunderbaldinger, P Bremer, C Matuszewski, L Marten, K Turetschek, K Rand, T TI Efficient radiological assessment of the internal snapping hip syndrome SO EUROPEAN RADIOLOGY LA English DT Article DE hip joint; iliopsoas tendon; plain radiographs; ultrasound; MR imaging ID ILIOPSOAS TENDON; IMAGING FINDINGS; BURSITIS AB The aim of this study was to evaluate the diagnostic value/significance of various imaging techniques for demonstrating the underlying causative pathology of clinically suspected internal snapping hip syndrome. We intended to define the most efficient diagnostic imaging algorithm that leads to a specific definite therapy for this rare hip disorder. The imaging studies of 54 patients (43 women, 11 men, average age 58 years) with the clinical suspicion of internal snapping hip syndrome were compared for their diagnostic value/significance for finding the underlying pathology. Radiological workup included plain radiographs of the pelvis and hip joints (n = 54), ultrasound (US) of the hip joints (n = 29), computed tomography (CT) of the pelvis and proximal femur (n = 17), and magnetic resonance imaging (MRI) of the pelvis/hip joint (n = 21). In order to establish an efficient diagnostic algorithm we compared the diagnostic value of each imaging technique alone and in combination with the other methods. The underlying causative pathology could be established in 37% of patients (n = 20) by the use of conventional radiographs alone and in 46% of the patients (n = 25) by US alone, and in combination in 83% of the patients (n = 45). By adding CT to the radiological workup, we established final diagnosis in 88% (in combination with X-ray; n = 15/17) and 94% (together with X-ray and US; n = 16/17) of the patients. Whenever MR imaging was used a causative pathology was found in all patients (100%; n = 21). The most efficient radiological algorithm in the assessment of patients with internal snapping hip syndrome is the combination of plain radiography and US. MR imaging can be retained for unresolved and difficult cases. C1 Univ Vienna, Dept Radiol, Vienna, Austria. Univ Munster, Inst Clin Radiol, D-4400 Munster, Germany. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Wunderbaldinger, P (reprint author), Univ Vienna, Dept Radiol, Vienna, Austria. NR 16 TC 12 Z9 13 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PY 2001 VL 11 IS 9 BP 1743 EP 1747 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 468HV UT WOS:000170752800024 PM 11511896 ER PT J AU Huisman, TAGM Holzmann, D Martin, E Willi, UV AF Huisman, TAGM Holzmann, D Martin, E Willi, UV TI Cerebral venous thrombosis in childhood SO EUROPEAN RADIOLOGY LA English DT Article DE dural sinus; CT; trauma; infection ID LATERAL SINUS THROMBOSIS; CHILDREN; COMPLICATIONS AB This was a retrospective study to determine different etiologies of cerebral venous thrombosis (CVT) in childhood and to correlate extent and location of thrombosis with the etiology and the age of the child as well as the final outcome. In addition, the radiologic approach is discussed. This was a retrospective analysis of 19 children with CVT The children were examined by contrast-enhanced dynamic CT. Radiologic findings were correlated with the etiology of CVT. Cerebral venous thrombosis is not as infrequent in children as has been thought. Cerebral venous thrombosis in children can occur due to trauma (n = 9), infections (n = 7), or coagulation disorders (n = 3). Extent and location of thrombosis, as well as complications, final outcome, and therapy, depend on the etiology. Computed tomography remains a valuable primary imaging modality in the diagnosis of CVT in the acutely injured or diseased child. C1 Univ Childrens Hosp Zurich, Dept Diagnost Imaging & Radiol, Zurich, Switzerland. Univ Childrens Hosp Zurich, Dept Otorhinolaryngol, Zurich, Switzerland. RP Huisman, TAGM (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St,Mail Code 149 2301, Boston, MA 02129 USA. NR 18 TC 23 Z9 24 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PY 2001 VL 11 IS 9 BP 1760 EP 1765 DI 10.1007/s003300100822 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 468HV UT WOS:000170752800027 PM 11511899 ER PT J AU Pandey, JP Cooper, GS Treadwell, EL Gilkeson, GS St Clair, EW Dooley, MA AF Pandey, JP Cooper, GS Treadwell, EL Gilkeson, GS St Clair, EW Dooley, MA TI Immunoglobulin GM and KM allotypes in systemic lupus erythematosus SO EXPERIMENTAL AND CLINICAL IMMUNOGENETICS LA English DT Article DE GM allotype; KM allotype; immunoglobulin; haplotype; linkage; disequilibrium; systemic lupus erythematosus ID AUTOIMMUNE-DISEASES; REVISED CRITERIA; ASSOCIATION; CLASSIFICATION; SCLEROSIS; GENETICS; LINKAGE; GENES; KAPPA; HLA AB Genetic variation in immunoglobulin gamma (GM) and kappa (KM) chains was associated with systemic lupus erythematosus (SLE) in some studies. However, the data are conflicting, and only one study examined associations in African-Americans. We examined GM and KM allotypes, by race, in a population-based case-control study of SLE. Sera from patients (n = 222) and controls (n = 273) were typed for GM and KM allotypes by a hemagglutination inhibition method. GM phenotypes were not significantly associated with SLE in African-Americans or Caucasians. However, the frequency of KM phenotypes in Caucasian patients was significantly different from that in controls (p = 0.032). KM3,3 was associated with an increased risk, whereas KM1,3 was associated with a lower relative risk of SLE. In African-Americans, however, the pattern of associations with KM phenotypes differed from that in Caucasians, and the overall difference between patients and controls was not statistically significant. Copyright (C) 2001 S. Karger AG, Basel. C1 Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Durham, NC USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Duke Univ, Med Ctr, Div Rheumatol Allergy & Clin Immunol, Durham, NC USA. Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USA. RP Pandey, JP (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. NR 27 TC 11 Z9 11 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-9670 J9 EXP CLIN IMMUNOGENET JI Exp. Clin. Immunogenet. PY 2001 VL 18 IS 3 BP 117 EP 122 DI 10.1159/000049190 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology GA 474WZ UT WOS:000171131000001 PM 11549840 ER PT J AU Andreassen, OA Ferrante, RJ Dedeoglu, A Albers, DW Klivenyi, P Carlson, EJ Epstein, CJ Beal, MF AF Andreassen, OA Ferrante, RJ Dedeoglu, A Albers, DW Klivenyi, P Carlson, EJ Epstein, CJ Beal, MF TI Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP SO EXPERIMENTAL NEUROLOGY LA English DT Article DE MPTP; malonate; free radicals; 3-nitropropionic acid; Parkinson's disease; Huntington's disease ID INCREASED OXIDATIVE DAMAGE; NEURODEGENERATIVE DISEASES; MUTANT MICE; LIQUID-CHROMATOGRAPHY; RAT STRIATUM; IN-VIVO; STRESS; LESIONS; NEURONS; NEUROTOXICITY AB There is substantial evidence implicating mitochondrial dysfunction and free radical generation as major mechanisms of neuronal death in neurodegenerative diseases. The major free radical scavenging enzyme in mitochondria is manganese superoxide dismutase (SOD2). In the present study we investigated the susceptibility of mice with a partial deficiency of SOD2 to the neurotoxins 1-methyl-4-phenyl-1,2,5,6-tetrahydro-pyridine (MPTP), 3-nitropropionic acid (3-NP), and malonate, which are commonly used animal models of Parkinson's and Huntington's disease, Heterozygous SOD2 knockout (SOD2(+/-)) mice showed no evidence of neuropathological or behavioral abnormalities at 2-4 months of age. Compared to littermate wild-type mice, mice with partial SOD2 deficiency showed increased vulnerability to dopamine depletion after systemic MPTP treatment and significantly larger striatal lesions produced by both 3-NP and malonate. SOD2(+/-) mice also showed an increased production of "hydroxyl" radicals after malonate injection measured with the salicylate hydroxyl radical trapping method. These results provide further evidence that reactive oxygen species play an important role in the neurotoxicity of MPTP, malonate, and 3-NP. These findings show that a subclinical deficiency in a free radical scavenging enzyme may act in concert with environmental toxins to produce selective neurodegeneration. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Bedford Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bedford, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Cornell Univ, Med Ctr, New York Hosp, New York, NY 10021 USA. RP Andreassen, OA (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. OI Dedeoglu, Alpaslan/0000-0003-1156-0874; Andreassen, Ole A./0000-0002-4461-3568 FU NIA NIH HHS [AG13846]; NINDS NIH HHS [NS35255, NS37102, NS38180] NR 36 TC 80 Z9 81 U1 0 U2 7 PU ACADEMIC PRESS INC 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 JAN PY 2001 VL 167 IS 1 BP 189 EP 195 DI 10.1006/exnr.2000.7525 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 392VH UT WOS:000166432900020 PM 11161607 ER PT J AU Orlando, LR Alsdorf, SA Penney, JB Young, AB AF Orlando, LR Alsdorf, SA Penney, JB Young, AB TI The role of group I and group II metabotropic glutamate receptors in modulation of striatal NMDA and quinolinic acid toxicity SO EXPERIMENTAL NEUROLOGY LA English DT Article DE striatum; excitotoxicity; mGluRs; N-methyl-D-aspartate; quinolinic acid; decortication ID EXCITOTOXIC NEURONAL DEATH; CORTICAL CELL-CULTURE; HUNTINGTONS-DISEASE; POTENTIATES NMDA; BASAL GANGLIA; 1-AMINOINDAN-1,5-DICARBOXYLIC ACID; PHENYLGLYCINE DERIVATIVES; NEUROPROTECTIVE ACTIVITY; SELECTIVE ACTIVATION; MGLUR AGONIST AB Excitotoxic lesions of the striatum are mediated by the combined activity of N-methyl-D-aspartate (NMDA) receptors and metabotropic glutamate receptors (mGluRs). Intrastriatal injection of the NMDA receptor agonists NMDA or quinolinic acid creates large lesions, but in rats that have been decorticated to remove endogenous glutamatergic input, NMDA and quinolinic acid are no longer toxic. We report that NMDA toxicity can be restored in decorticated animals by coinjection of the group I mGluR agonists t-ACPD, t-ADA, or CHPG.. In addition, injections of two group I mGluR antagonists, AIDA and (S)-4C3HPG, can protect against striatal lesions produced by quinolinic acid or NMDA injections in normal rats by blocking activation of group I mGluRs. The group II mGluR agonist APDC fails to protect against quinolinic acid or NMDA toxicity in intact animals or to restore NMDA toxicity in decorticated animals, suggesting that the role of group II receptors in this excitotoxic model is minimal. These observations confirm the important role of group I mGluRs in excitotoxicity and identify these receptors as promising targets for therapeutic intervention in neurodegenerative disease processes, (C) 2001 Academic Press. C1 Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Orlando, LR (reprint author), Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. FU NIA NIH HHS [AG13617]; NINDS NIH HHS [NS31579] NR 58 TC 48 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC 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 JAN PY 2001 VL 167 IS 1 BP 196 EP 204 DI 10.1006/exnr.2000.7542 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 392VH UT WOS:000166432900021 PM 11161608 ER PT S AU Leaf, A AF Leaf, A BE Hamazaki, T Okuyama, H TI Electrophysiologic basis for the antiarrhythmic and anticonvulsant effects of omega 3 polyunsaturated fatty acids SO FATTY ACIDS AND LIPIDS-NEW FINDINGS SE WORLD REVIEW OF NUTRITION AND DIETETICS LA English DT Proceedings Paper CT 4th Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids (ISSFAL) CY JUN 04-09, 2000 CL TSUKUBA, JAPAN SP Int Soc Study Fatty Acids & Lipids, DHA & EPA Assoc, F Hoffmann, La Roche AG, Japan Federat Econ Org, Japan Soc Lipid Nutrit, Kentech Co, LTD, Osaka Pharmaceut Manufacturers Assoc, Pharmaceut Manufacturers Assoc Tokyo, Sankyo Fdn Life Sci, Uehara Mem Fdn ID RAT CARDIAC MYOCYTES; LONG-CHAIN; VENTRICULAR MYOCYTES; NA+ CHANNELS; ARRHYTHMIAS; PREVENTION; CURRENTS C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL62284]; NIDDK NIH HHS [DK38165] NR 20 TC 5 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 3-8055-7182-8 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2001 VL 88 BP 72 EP 78 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA BS86L UT WOS:000171272900011 PM 11935974 ER PT J AU Smith, JJ Agraz, JA AF Smith, JJ Agraz, JA TI Federal regulation of single-use medical devices: A revised FDA policy SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID REUSE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. CIMIT, Boston, MA USA. Boston Univ, Sch Law, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Smith, JJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 13 TC 2 Z9 2 U1 0 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2001 VL 56 IS 3 BP 305 EP 316 PG 12 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 506FJ UT WOS:000172958900005 PM 11944641 ER PT J AU Kochevar, IE Zhuang, SG Lynch, MC AF Kochevar, IE Zhuang, SG Lynch, MC TI MAP kinase signaling, oxidative stress and apoptosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA P13 BP S8 EP S8 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200014 ER PT J AU Lipinski, B AF Lipinski, B TI Evidence of reductive properties of transition metal-induced hydroxyl radicals. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Genet, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 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. PY 2001 VL 31 SU 1 MA 10 BP S13 EP S13 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200028 ER PT J AU Mitsumoto, A Kochevar, IE AF Mitsumoto, A Kochevar, IE TI Redox regulation of tropoelastin mRNA expression in human dermal fibroblasts in response to TGF beta SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 165 BP S58 EP S58 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200180 ER PT J AU Van Remmen, H Chen, X Mele, J Ran, Q Shibatani, T Prolla, T Richardson, A AF Van Remmen, H Chen, X Mele, J Ran, Q Shibatani, T Prolla, T Richardson, A TI Altered sensitivity to gamma-irradiation and paraquat in mice with genetically modulated antioxidant defense systems SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 382 BP S128 EP S128 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200397 ER PT S AU Dwinell, MR Kazemi, H Lam, JT Powell, FL AF Dwinell, MR Kazemi, H Lam, JT Powell, FL BE Poon, CS Kasemi, H TI Central amino acid neurotransmitters, ventilatory output and metabolism during acute hypoxia in anesthetized rats SO FRONTIERS IN MODELING AND CONTROL OF BREATHING: INTERGATION AT MOLECULAR, CELLULAR, AND SYSTEMS LEVELS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 8th International Oxford Conference on Frontiers in Modeling and Control of Breathing CY OCT 11-15, 2000 CL N FALMOUTH, MASSACHUSETTS SP Amer Physiol Soc, Physiol Soc, Whitaker Fdn, Respirat Physiol, GlaxosmithKline Inc, Harvard Apparatus Inc, Amer Thorac Soc C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, White Mt Res Stn, La Jolla, CA 92093 USA. RP Dwinell, MR (reprint author), Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. FU NHLBI NIH HHS [HL-17731, HL-07212] NR 9 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46647-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 499 BP 291 EP 296 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Neurosciences; Respiratory System SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology; Respiratory System GA BT28T UT WOS:000172534500046 PM 11729894 ER PT S AU Systrom, DM Hrovat, M Oelberg, D Kazemi, H AF Systrom, DM Hrovat, M Oelberg, D Kazemi, H BE Poon, CS Kasemi, H TI Skeletal muscle chemoreflex in exercise ventilatory control SO FRONTIERS IN MODELING AND CONTROL OF BREATHING: INTERGATION AT MOLECULAR, CELLULAR, AND SYSTEMS LEVELS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 8th International Oxford Conference on Frontiers in Modeling and Control of Breathing CY OCT 11-15, 2000 CL N FALMOUTH, MASSACHUSETTS SP Amer Physiol Soc, Physiol Soc, Whitaker Fdn, Respirat Physiol, GlaxosmithKline Inc, Harvard Apparatus Inc, Amer Thorac Soc ID GROUP-IV AFFERENTS; DYNAMIC EXERCISE; GROUP-III; CIRCULATORY OCCLUSION; MUSCULAR-CONTRACTION; MAGNETIC-RESONANCE; PRESSOR-RESPONSE; HINDLIMB MUSCLE; HYPERPNEA; GLUTAMATE C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Yale Univ, Sch Med, Danbury Hosp, Pulm & Crit Care Div, Danbury, CT 06810 USA. RP Systrom, DM (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. FU NCI NIH HHS [R21 CA87734]; NHLBI NIH HHS [K24 HL04022-02] NR 31 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46647-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 499 BP 343 EP 348 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Neurosciences; Respiratory System SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology; Respiratory System GA BT28T UT WOS:000172534500055 PM 11729905 ER PT J AU Poneros, JM Brand, S Bouma, BE Tearney, GJ Compton, CC Nishioka, NS AF Poneros, JM Brand, S Bouma, BE Tearney, GJ Compton, CC Nishioka, NS TI Diagnosis of specialized intestinal metaplasia by optical coherence tomography SO GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; BARRETTS-ESOPHAGUS; ADENOCARCINOMA; DYSPLASIA; BIOPSY; TISSUE AB Background & Aims: Optical coherence tomography (OCT) is an imaging technique that produces high-resolution cross-sectional images in vivo. The aim of this study was to establish the sensitivity and specificity of OCT for diagnosing specialized intestinal metaplasia (SIM), Methods: OCT was used to image the stomach and esophagus of 121 patients. A total of 288 biopsy-correlated OCT images were acquired. OCT criteria for SIM were formulated by analyzing 75 images of SIM. The SIM image criteria were retrospectively tested by applying them to images of gastric, squamous, SIM, and cardiac epithelium. The criteria were then tested prospectively to determine the sensitivity and specificity of OCT for diagnosing SIM. Results: OCT images of SIM are characterized by (1) absence of the layered structure of normal squamous epithelium and the vertical "pit and crypt" morphology of gastric mucosa, (2) disorganized architecture with inhomogeneous tissue contrast and an irregular mucosal surface, and (3) presence of submucosal glands, These criteria were 100% sensitive and 93% specific for SIM when applied retrospectively and 97% sensitive and 92% specific when tested prospectively, Conclusions: OCT is highly sensitive and specific for SIM and may aid in the diagnosis and surveillance of this preneoplastic lesion. C1 Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Sch Med, BAR 703,50 Blossom St, Boston, MA 02114 USA. EM norm@wlp.mgh.harvard.edu FU NIDDK NIH HHS [T32 DK07191] NR 29 TC 145 Z9 150 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2001 VL 120 IS 1 BP 7 EP 12 DI 10.1053/gast.2001.20911 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 392BM UT WOS:000166390800005 PM 11208708 ER PT J AU Bitton, A Peppercorn, MA Antonioli, DA Niles, JL Shah, S Bousvaros, A Ransil, B Wild, G Cohen, A Edwardes, MDD Stevens, AC AF Bitton, A Peppercorn, MA Antonioli, DA Niles, JL Shah, S Bousvaros, A Ransil, B Wild, G Cohen, A Edwardes, MDD Stevens, AC TI Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Annual Digestive Disease Week/97th Annual Meeting of the American-Gastroenterological-Association CY MAY 17-20, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Gastroenterol Assoc ID INFLAMMATORY BOWEL-DISEASE; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; CROHNS-DISEASE; 1ST YEAR; REMISSION; INTERLEUKIN-6; SPECIFICITY; MAINTENANCE; MESALAZINE; POUCHITIS AB Background & Aims: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. We aimed to assess whether clinical, biological, and histologic parameters in quiescent UC predict time to clinical relapse. Methods: Seventy-four patients with clinically and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse. Serum erythrocyte sedimentation rate; C-reactive protein, interleukin (IL)-1 beta, IL-6, and IL-15 values; anti-neutrophil cytoplasmic antibody titers; and rectal biopsy specimens were obtained at baseline, at 6 and 12 months, and/or at relapse, Multivariate survival analysis was performed to determine independent predictors of clinical relapse. Results: Twenty-seven patients relapsed (19/42 women; 8/32 men). Multivariate Cox regression analysis retained younger age (P = 0.003; hazard ratio, 0.4 per decade), greater number of prior relapses in women (P < 0.001; hazard ratio, 1.6 per prior relapse), and basal plasmacytosis (P = 0.003; hazard ratio, 4.5) on rectal biopsy specimens as predictors of shorter time to clinical relapse. Kaplan-Meier survival curves showed the 20-30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse. Conclusions: Younger age, multiple previous relapses (for women), and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse. These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy. C1 Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada. Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Childrens Hosp, Div Gastroenterol, Nutr Unit, Boston, MA 02115 USA. McGill Univ, Ctr Hlth, Dept Med, Montreal, PQ, Canada. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. RP Bitton, A (reprint author), Royal Victoria Hosp, Div Clin Epidemiol, 687 Pine Ave, Montreal, PQ H3A 1A1, Canada. NR 34 TC 216 Z9 222 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2001 VL 120 IS 1 BP 13 EP 20 DI 10.1053/gast.2001.20912 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 392BM UT WOS:000166390800006 PM 11208709 ER PT J AU Luster, AD AF Luster, AD TI Chemokines regulate lymphocyte homing to the intestinal mucosa SO GASTROENTEROLOGY LA English DT Editorial Material ID T-CELLS; IP-10; EXPRESSION; SUBSETS; MIG C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 29 TC 22 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2001 VL 120 IS 1 BP 291 EP 294 DI 10.1053/gast.2001.21403 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 392BM UT WOS:000166390800036 PM 11208738 ER PT J AU Elenbaas, B Spirio, L Koerner, F Fleming, MD Zimonjic, DB Donaher, JL Popescu, NC Hahn, WC Weinberg, RA AF Elenbaas, B Spirio, L Koerner, F Fleming, MD Zimonjic, DB Donaher, JL Popescu, NC Hahn, WC Weinberg, RA TI Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells SO GENES & DEVELOPMENT LA English DT Article DE transformation; mammary; epithelial; ras; c-myc; fibroblast ID HUMAN PAPILLOMAVIRUS TYPE-16; NUDE-MICE; TELOMERASE ACTIVITY; HUMAN FIBROBLASTS; GENE; PROGRESSION; EXPRESSION; RAS; GROWTH; P53 AB A number of genetic mutations have been identified in human breast cancers, yet the specific combinations of mutations required in concert to form breast carcinoma cells remain unknown. One approach to identifying the genetic and biochemical alterations required for this process involves the transformation of primary human mammary epithelial cells (HMECs) to carcinoma cells through the introduction of specific genes. Here we show that introduction of three genes encoding the SV40 large-T antigen, the telomerase catalytic subunit, and an H-Ras oncoprotein into primary HMECs results in cells that form tumors when transplanted subcutaneously or into the mammary glands of immunocompromised mice. The tumorigenicity of these transformed cells was dependent on the level of ras oncogene expression. Interestingly, transformation of HMECs but not two other human cell types was associated with amplifications of the c-myc oncogene, which occurred during the in vitro growth of the cells. Tumors derived from the transformed HMECs were poorly differentiated carcinomas that infiltrated through adjacent tissue. When these cells were injected subcutaneously, tumors formed in only half of the injections and with an average latency of 7.5 weeks. Mixing the epithelial tumor cells with Matrigel or primary human mammary fibroblasts substantially increased the efficiency of tumor formation and decreased the latency of tumor formation, demonstrating a significant influence of the stromal microenvironment on tumorigenicity. Thus, these observations establish an experimental system for elucidating both the genetic and cell biological requirements for the development of breast cancer. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Weinberg, RA (reprint author), MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. FU NCI NIH HHS [5 P01 CA80111-02, P01 CA080111] NR 51 TC 550 Z9 564 U1 2 U2 18 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2001 VL 15 IS 1 BP 50 EP 65 DI 10.1101/gad.828901 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 392MP UT WOS:000166415500007 PM 11156605 ER PT J AU Dahia, PLM Eng, C AF Dahia, PLM Eng, C TI Hereditary endocrine neoplasias: Fundamental insights and the practice of clinical cancer genetics SO GENETIC DISORDERS OF ENDOCRINE NEOPLASIA SE FRONTIERS OF HORMONE RESEARCH LA English DT Review ID TUMOR-SUPPRESSOR GENES; SINGLE-NUCLEOTIDE POLYMORPHISMS; DNA METHYLATION; HIRSCHSPRUNG-DISEASE; RISK ASSESSMENT; EXPRESSION; PATTERNS; TUMORIGENESIS; INACTIVATION; PROGRESSION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA. RP Dahia, PLM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,SM1010, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 NR 64 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 J9 FRONT HORM RES JI Front.Horm.Res. PY 2001 VL 28 BP 8 EP 19 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BS89B UT WOS:000171319400003 PM 11443854 ER PT J AU Aguiar, RCT Dahia, PLM AF Aguiar, RCT Dahia, PLM TI Identification and characterization of disease-related genes: Focus on endocrine neoplasias SO GENETIC DISORDERS OF ENDOCRINE NEOPLASIA SE FRONTIERS OF HORMONE RESEARCH LA English DT Review ID TUMOR-SUPPRESSOR GENE; COMPARATIVE GENOMIC HYBRIDIZATION; PAPILLARY THYROID CARCINOMAS; FRAGMENT LENGTH POLYMORPHISMS; POLYMERASE CHAIN-REACTION; RILEY-RUVALCABA-SYNDROME; RET PROTOONCOGENE; LINKAGE MAP; EXPRESSION PROFILES; HUMAN-CHROMOSOMES C1 Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Aguiar, RCT (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol, 44 Binney St M513, Boston, MA 02115 USA. NR 142 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 J9 FRONT HORM RES JI Front.Horm.Res. PY 2001 VL 28 BP 20 EP 49 PG 30 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BS89B UT WOS:000171319400004 PM 11443852 ER PT J AU Iliopoulos, O AF Iliopoulos, O TI Von Hippel-Lindau disease: Genetic and clinical observations SO GENETIC DISORDERS OF ENDOCRINE NEOPLASIA SE FRONTIERS OF HORMONE RESEARCH LA English DT Review ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; CENTRAL-NERVOUS-SYSTEM; ENDOCRINE NEOPLASIA TYPE-2; ENDOLYMPHATIC SAC TUMORS; ELONGIN BC COMPLEX; RNA-POLYMERASE-II; SPORADIC CEREBELLAR HEMANGIOBLASTOMAS; BIOLOGICALLY-ACTIVE PRODUCT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. RP Iliopoulos, O (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Bldg 149,Room 7405,St 13th, Charlestown, MA 02129 USA. NR 221 TC 16 Z9 16 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 J9 FRONT HORM RES JI Front.Horm.Res. PY 2001 VL 28 BP 131 EP 166 PG 36 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BS89B UT WOS:000171319400008 PM 11443850 ER PT J AU Bertram, L Hayward, B Lake, SL Falls, K Van Eerdewegh, P Blacker, D AF Bertram, L Hayward, B Lake, SL Falls, K Van Eerdewegh, P Blacker, D TI Family-based tests of association in the presence and absence of known linkage SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 12 (GAW12) CY OCT 23-26, 2000 CL SAN ANTONIO, TEXAS DE asthma genetics; empirical variance estimation; FBAT; TDT ID TRANSMISSION/DISEQUILIBRIUM TEST; SIBSHIP TEST; DISEQUILIBRIUM; GENE AB Correlation among sibling marker genotypes may invalidate the results of family-based tests of association in the presence of linkage. We apply an empirical variance estimation method, which is implemented in the program package FBAT, on Caucasian families with asthma in the presence and absence of linkage and compare the results with those obtained using the TDT (TDTEX-PAIRS) on the same data sets. Our results indicate that both tests generally perform comparably in either setting. ((C))2001 Wiley-Liss, Inc. C1 Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. Genome Therapeut Corp, Waltham, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gerontol Res Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Unit, Charlestown, MA USA. RP Blacker, D (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Gerontol Res Unit, 149 13th St, Charlestown, MA 02129 USA. RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NCRR NIH HHS [1 P41 RR03655]; NIMH NIH HHS [R01MH59632, R01MH60009] NR 16 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S292 EP S297 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700055 PM 11793685 ER PT J AU Page, GP Wilcox, MA Occhiuto, J Adak, S Neuberg, D Bajorunaite, R George, V AF Page, GP Wilcox, MA Occhiuto, J Adak, S Neuberg, D Bajorunaite, R George, V TI Comparison of the QTDT analysis for IgE in the CSGA data set SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 12 (GAW12) CY OCT 23-26, 2000 CL SAN ANTONIO, TEXAS DE chromosome 5; IgE; QTDT ID QUANTITATIVE TRAITS; TRANSMISSION-DISEQUILIBRIUM; ASSOCIATION; TESTS AB Over the past few years at least 13 transmission/disequilibrium test (TDT)-based tests have been developed for quantitative (Q) traits for the assessment of association or linkage in the presence of the other. A total of six of these QTDT methods were used to analyze log(10)IgE in the Collaborative Study on the Genetics of Asthma data set. Only moderate agreement was found between the tests. The results of the QTDT analyses were only slightly affected by the use of gender and age as covariates. Results from analysis of IgE and log(10)IgE were inconsistent. Our conclusion is that there is only modest agreement among the QTDT methods examined, covariates should be used even if they have a small effect, and that data should be normalized before analysis. ((C))2001 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29524 USA. Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Dept Environm Hlth, Cambridge, MA 02138 USA. Harvard Univ, Dept Biostat, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. RP Page, GP (reprint author), Med Univ S Carolina, Dept Biometry, 135 Rutledge Ave,Suite 1148, Charleston, SC 29524 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S312 EP S316 PG 5 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700059 PM 11793690 ER PT J AU Reinhart, BJ Ruvkun, G AF Reinhart, BJ Ruvkun, G TI Isoform-specific mutations in the Caenorhabditis elegans heterochronic gene lin-14 affect stage-specific patterning SO GENETICS LA English DT Article ID POSTEMBRYONIC DEVELOPMENTAL EVENTS; C-ELEGANS; GRADIENT MORPHOGEN; DROSOPHILA EMBRYO; SHOOT DEVELOPMENT; PROTEIN ISOFORMS; TEMPORAL CONTROL; CELL LINEAGES; EXPRESSION; SWITCH AB The Caenorhabditis elegans heterochronic gene lin-14 specifies the temporal sequence of postembryonic developmental events. lin-14, which encodes differentially spliced LIN-14A and LIN-14B1/B2 protein isoforms, acts at distinct times during the first larval stage to specify first and second larval stage-specific cell lineages. Proposed models for the molecular basis of these two lin-14 gene activities have included the production of functionally distinct isoforms and the generation of a temporal gradient of LIN-14 protein. We report here that loss of the LIN-14B1/B2 isoforms alone affects one of the two lin-14 temporal patterning functions, the specification of second lan al stage lineages. A temporal expression difference between LIN-14A and LIN-14B1/B2 is not responsible for the stage-specific phenotype: protein levels of all LIN-14 isoforms are high in early first larval stage animals and decrease during the first larval stage. However, LIN-14A can partially substitute for LIN-14B1/B2 when expressed at a higher-than-normal level in the late L1 stage. These data indicate that LIN-14B1/B2 isoforms do not provide a distinct function of the lin-14 locus in developmental timing but rather mall contribute to an overall level of LIN-14 protein that is the critical determinant of temporal cell fate. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman Bldg,8th Floor,50 Blossom St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM44619] NR 45 TC 25 Z9 26 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2001 VL 157 IS 1 BP 199 EP 209 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 391MH UT WOS:000166359400017 PM 11139502 ER PT B AU Saporito, JW AF Saporito, JW BE Kelly, TB BermanRossi, T Palombo, S TI Group work for heterosexual couples of mixed HIV status SO GROUP WORK: STRATEGIES FOR STRENGTHENING RESILIENCY LA English DT Proceedings Paper CT 20th Annual Symposium on Social Work with Groups CY OCT 15-18, 1998 CL MIAMI, FL SP Barry Univ Sch Social Work C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA BN 0-7890-1472-6 PY 2001 BP 181 EP 201 PG 21 WC Social Work SC Social Work GA BT87C UT WOS:000174318600011 ER PT J AU Cameron, CL Cella, D Herndon, JE Kornblith, AB Zuckerman, E Henderson, E Weiss, RB Cooper, MR Silver, RT Leone, L Canellos, GP Peterson, BA Holland, JC AF Cameron, CL Cella, D Herndon, JE Kornblith, AB Zuckerman, E Henderson, E Weiss, RB Cooper, MR Silver, RT Leone, L Canellos, GP Peterson, BA Holland, JC TI Persistent symptoms among survivors of Hodgkin's disease: An explanatory model based on classical conditioning SO HEALTH PSYCHOLOGY LA English DT Article DE Hodgkin's disease; anticipatory side effects; nausea; psychological distress; classical conditioning ID CANCER-CHEMOTHERAPY; ANTICIPATORY NAUSEA; RECEIVING CHEMOTHERAPY; PREVALENCE; MANAGEMENT; ANXIETY AB Persistent symptoms of nausea, distress, and vomiting triggered by reminders of cancer treatment were examined among 273 Hodgkin's disease survivors, 1 to 20 years posttreatment. Prevalence rates were high for distress and nausea but low for vomiting. Retrospective report of anticipatory symptoms during treatment was the strongest predictor of persistent symptoms, suggesting that treatment-induced symptoms are less likely to persist if conditioning does not occur initially. Time since treatment was also a significant predictor, with patients more recently treated more likely to experience persistent symptoms. Thus, an explanatory model based on classical conditioning theory successfully predicted presence of persistent symptoms. Symptoms also were associated with ongoing psychological distress, suggesting that quality of life is diminished among survivors with persistent symptoms. Recommendations for prevention and treatment of symptoms are discussed. C1 Evanston NW Healthcare, Ctr Outcomes Res & Educ, Evanston, IL 60201 USA. Duke Univ, Stat Off, Durham, NC 27706 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Psychiat, New York, NY 10021 USA. Vet Affairs Western New York Healthcare, Dept Med, Buffalo, NY USA. Walter Reed Army Med Ctr, Dept Med, Bethesda, MD USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27109 USA. Cornell Univ, Med Ctr, New York Hosp, Dept Med, New York, NY 10021 USA. Rhode Isl Hosp, Dept Med, Providence, RI USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. RP Cella, D (reprint author), Evanston NW Healthcare, Ctr Outcomes Res & Educ, 1033 Univ Pl,Suite 100, Evanston, IL 60201 USA. FU NCI NIH HHS [CA 04326, CA 11028, CA 32291] NR 25 TC 13 Z9 13 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 2001 VL 20 IS 1 BP 71 EP 75 DI 10.1037/0278-6133.20.1.71 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA 392YX UT WOS:000166441300009 PM 11199068 ER PT S AU Walter, CA Zhou, ZQ Manguino, D Ikeno, Y Reddick, R Nelson, J Intano, G Herbert, DC McMahan, CA Hanes, M AF Walter, CA Zhou, ZQ Manguino, D Ikeno, Y Reddick, R Nelson, J Intano, G Herbert, DC McMahan, CA Hanes, M BE Park, SC Hwang, ES Kim, HS Park, WY TI Health span and life span in transgenic mice with modulated DNA repair SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ DE transgenic mice; alkylation damage; aging; hepatocellular carcinoma; MGMT ID MUTATION FREQUENCY; HUMAN-LYMPHOCYTES; CHROMOSOMAL-ABERRATIONS; DIETARY RESTRICTION; HUMAN TRANSFERRIN; OLD MICE; AGE; DAMAGE; BRAIN; CELLS AB One way to better understand the contribution of DNA repair, DNA damage, and mutagenesis in aging would be to enhance DNA repair activity, lower DNA damage, and lower mutagenesis. Because the repair protein O-6-methylguanine-DNA methyltransferase (MGMT) acts alone and stoichiometrically, the human MGMT (hMGMT) cDNA was selected to test the feasibility of enhancing DNA repair activity in transgenic mice. MGMT activity is largely responsible for ameliorating the deleterious effects of O-6-methylguanine (O(6)mG) lesions in DNA in a direct reversal mechanism. A transgene was constructed consisting of a portion of the human transferrin (TF) promoter and hMGMT cDNA such that hMGMT is expressed in transgenic mouse brain and liver. Expression of hMGMT was associated with a significant reduction in the occurrence of an age-related hepatocellular carcinoma in male mice at 15 months of age. Longitudinal and cross-sectional studies were initiated to determine whether the reduced incidence of hepatocellular carcinoma would impact median or maximum life span. The cross-sectional study performed on 15-month-old male animals confirmed the reduced occurrence of spontaneous hepatocellular carcinoma. At 30 months of age, however, the occurrence of hepatocellular carcinoma in at least one transgenic line was similar to that for nontransgenic animals. The longitudinal study is ongoing; however, at pre-sent no significant differences in life span have been detected. Tissues expressing the MGMT transgene also displayed greater resistance to alkylation-induced tumor formation. These results suggest that transgenes can be used to direct enhanced DNA repair gene expression and that enhanced expression can protect animals from certain spontaneous and induced tumors. 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 Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Lab Anim Resources, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Walter, CA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, Mail Code 7762,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [AG13319, AG13560]; NIEHS NIH HHS [ES05798] NR 33 TC 12 Z9 13 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 132 EP 140 PG 9 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700013 PM 11795504 ER PT S AU Choi, JK Lee, HP Choi, EK Jin, JK Lee, HG Wasco, W Buxbaum, JD Carp, RI Kim, YS AF Choi, JK Lee, HP Choi, EK Jin, JK Lee, HG Wasco, W Buxbaum, JD Carp, RI Kim, YS BE Park, SC Hwang, ES Kim, HS Park, WY TI Increased expression of calsenilin in the brains of scrapie-infected mice SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ C1 Hallym Acad Sci, Inst Environm & Life Sci, Chunchon, South Korea. Hallym Univ, Coll Med, Dept Microbiol, Chunchon, South Korea. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Genet & Aging Unit, Cambridge, MA USA. Mt Sinai Sch Med, Dept Psychiat & Neurobiol, New York, NY USA. New York State Inst Basic Res Dev Disabil, New York, NY USA. RP Choi, JK (reprint author), Hallym Acad Sci, Inst Environm & Life Sci, Chunchon, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 363 EP 363 PG 1 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700052 ER PT S AU Jin, JK Choi, JK Kim, JI Lee, HG Wasco, W Buxbaum, JD Carp, RI Kim, YS Choi, EK AF Jin, JK Choi, JK Kim, JI Lee, HG Wasco, W Buxbaum, JD Carp, RI Kim, YS Choi, EK BE Park, SC Hwang, ES Kim, HS Park, WY TI Overexpression of calsenilin in sporadic Alzheimer's disease brain SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ C1 Hallym Acad Sci, Inst Environm & Life Sci, Chunchon, South Korea. Hallym Univ, Coll Med, Dept Microbiol, Chunchon, South Korea. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, Cambridge, MA USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. New York State Inst Basic Res Dev Disabil, New York, NY USA. RP Jin, JK (reprint author), Hallym Acad Sci, Inst Environm & Life Sci, Chunchon, South Korea. RI Lee, Hyoung-gon/A-9637-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 373 EP 373 PG 1 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700062 ER PT B AU Birjiniuk, V Whitehead, S Schneider, JW AF Birjiniuk, V Whitehead, S Schneider, JW BE Kimchi, A TI Beating adult human myocardium in vitro SO HEART DISEASE: NEW TRENDS IN RESEARCH, DIAGNOSIS AND TREATMENT LA English DT Proceedings Paper CT 2nd International Congress on Heart Disease - New Trends in Research, Diagnosis and Treatment CY JUL 21-24, 2001 CL WASHINGTON, D.C. ID CARDIOMYOCYTES AB We have successfully cultured and maintained viable and functional adult human cardiomyocytes in vitro. These cells demonstrated spontaneous and repetitive contraction and maintained structural organization characteristic of working muscle. DNA synthesis by these muscle fibers was documented and adenoviral gene transfer was substantiated. One potential implication of these data is that such cultured myocardium could provide an expandable source of cardiomyocytes to support the contractile function of the failing heart. C1 VA Boston Healthcare Syst, Div Cardiol, W Roxbury, MA USA. RP Birjiniuk, V (reprint author), VA Boston Healthcare Syst, Div Cardiol, W Roxbury, MA USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 0-9706680-3-1 PY 2001 BP 25 EP 27 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BT13T UT WOS:000172045400004 ER PT J AU Oesterle, SN AF Oesterle, SN TI Where cardiac surgery and interventional cardiology merge: The future of catheter-based interventions for cardiovascular disease SO HEART SURGERY FORUM LA English DT Article; Proceedings Paper CT 3rd Annual Minimally Invasive Cardiac Surgery Symposium (MICS III) CY MAY 26-27, 2001 CL KEY WEST, FL ID UTILIZING RADIOACTIVE MICROSPHERES; COMPARING CORONARY ANGIOPLASTY; ATRIAL-FIBRILLATION; BYPASS-SURGERY; HEART-FAILURE; MYOCARDIAL REVASCULARIZATION; SELECTIVE ARTERIALIZATION; MYOBLAST TRANSPLANTATION; INFARCTED MYOCARDIUM; RANDOMIZED TRIAL C1 Massachusetts Gen Hosp, Invas Cardiol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oesterle, SN (reprint author), Massachusetts Gen Hosp, Invas Cardiol Serv, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. EM oesterle.stephen@mgh.harvard.edu NR 44 TC 3 Z9 3 U1 0 U2 0 PU FORUM MULTIMEDIA PUBLISHING, LLC PI CHARLOTTESVILLE PA 375 GREENBRIER DR, CHARLOTTESVILLE, VA 22901 USA SN 1098-3511 J9 HEART SURG FORUM JI Heart Surg. Forum PY 2001 VL 4 IS 4 BP 290 EP 296 AR 2001-5325 PG 7 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 509ET UT WOS:000173133900002 PM 11827853 ER PT J AU Marcus, EA Scott, DR AF Marcus, EA Scott, DR TI Cell lysis is responsible for the appearance of extracellular urease in Helicobacter pylori SO HELICOBACTER LA English DT Article DE urease; protein export; gfp; autolysis ID CYTOPLASMIC UREASE; GASTRIC-CARCINOMA; NEGATIVE MUTANT; ACID RESISTANCE; PROTEIN; EXPRESSION; INFECTION; PH; PATHOGENESIS; LOCALIZATION AB Background. Helicobacter pylori is a neutralophilic bacterium that colonizes the acidic human gastric surface using the neutralizing capacity of a constitutively produced urease. Urease is present both in the cytoplasm and bound to the outside surface of the bacteria. The origin of the surface urease continues to be controversial. This study provides additional evidence that the origin of surface urease is cell lysis, not secretion. Methods. H. Pylori was transformed with a plasmid encoding green fluorescent protein (GFP), a non-native cytoplasmic protein. Cultures supplemented with beta -cyclodextrin or horse serum were collected over various time periods and spun through a ficoll cushion to gently separate whole bacteria from released protein. The pellet and supernatant fractions were analyzed by fluorimetry, SDS-PAGE and Coomassie blue or Western analysis. Results. GFP fluorescence and antigenic reactivity in the supernatant increased at each time point. GFP, the non-native cytoplasmic protein, and UreB, a native cytoplasmic protein, increased over time in the supernatant and both proteins were always present in the pellet fraction. UreI, an inner membrane protein, was only present in the pellet fraction. beta -galactosidase, a protein not found in H. pylori, was used as a negative control. Conclusions. Since it is unlikely that there is an intrinsic secretion system for GFP, a non-native protein, its increasing presence over time in the supernate fraction along with UreB, and retention of UreI in the pellet fraction implies that cell lysis accounts for the presence of urease on the surface of H. pylori. C1 Univ Calif Los Angeles, VAGLAHS, Dept Physiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Scott, DR (reprint author), Univ Calif Los Angeles, VAGLAHS, Dept Physiol, 11301 Wilshire Blvd,Bldg 113,Room 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK40615]; PHS HHS [17294, 41301] NR 33 TC 36 Z9 37 U1 0 U2 6 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PY 2001 VL 6 IS 2 BP 93 EP 99 DI 10.1046/j.1523-5378.2001.00014.x PG 7 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 444YV UT WOS:000169428900003 PM 11422463 ER PT S AU Ogawa, M Tajima, F Ito, T Sato, T Laver, JH Deguchi, T AF Ogawa, M Tajima, F Ito, T Sato, T Laver, JH Deguchi, T BE Orlic, D Brummendorf, TH Sharkis, SJ Kanz, L TI CD34 expression by murine hematopoietic stem cells - Developmental changes and kinetic alterations SO HEMATOPOIETIC STEM CELLS 2000 BASIC AND CLINICAL SCIENCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Hematopoietic Stem Cells: Genetics and Medicine CY SEP 14-16, 2000 CL TUBINGEN, GERMANY SP AMGEN, KIRIN DE CD34; hematopoietic stem cells; developmental changes ID PERIPHERAL-BLOOD; MARROW-CELLS; BONE-MARROW; IN-VIVO; TRANSPLANTATION; PROGENITOR AB For more than a decade it was believed that hematopoietic stem cells express CD34. However, this dogma was recently challenged by the observation that stem cells of normal adult mice are CD34(-). In order to clarify the controversy, we carried out systematic examination of stem cells by using C57BL/6 mice that are congenic for Ly-5. As reported previously, stem cells in the normal adult mice were CD34(-). However, stem cells stimulated in vivo by 5-flourouracil injection or in vitro by a combination of interleukin-11 and steel factor were CD34(+). The activated CD34(+) stem cells reverted to CD34(-) when the recipients' marrow achieved steady state. The majority of G-CSF-mobilized stem cells also were CD34(+) and reverted to CD34(-) under steady-state conditions. Most recently, we examined the developmental changes of stem cell CD34 expression. In order to gain information on the total population of stem cells we prepared CD34(+) and CD34(-) populations of mononuclear cells without prior enrichment and studied their engrafting potentials. All stem cells from perinatal to 5-week-old mice were CD34(+). In 7-week-old mice CD34(-) stem cells began to emerge, and the majority of the stem cells were CD34(-) in the 10- and 20-week-old mice. An estimated 20% of the adult stem cells expressed CD34. These observations provide insight into the current controversy regarding CD34 expression by adult hematopoietic stem cells. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29401 USA. Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 25 TC 34 Z9 35 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-295-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 938 BP 139 EP 145 PG 7 WC Cell Biology; Multidisciplinary Sciences SC Cell Biology; Science & Technology - Other Topics GA BT12U UT WOS:000172028500016 PM 11458501 ER PT S AU Manz, MG Traver, D Akashi, K Merad, M Miyamoto, T Engleman, EG Weissman, IL AF Manz, MG Traver, D Akashi, K Merad, M Miyamoto, T Engleman, EG Weissman, IL BE Orlic, D Brummendorf, TH Sharkis, SJ Kanz, L TI Dendritic cell development from common myeloid progenitors SO HEMATOPOIETIC STEM CELLS 2000 BASIC AND CLINICAL SCIENCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Hematopoietic Stem Cells: Genetics and Medicine CY SEP 14-16, 2000 CL TUBINGEN, GERMANY SP AMGEN, KIRIN DE dendritic cells; hematopoietic progenitors; lineage origin ID MOUSE BONE-MARROW; T-CELLS; MUTANT MICE; IN-VIVO; CD8-ALPHA(+); LINEAGES; PHENOTYPE; SUBCLASS; THYMUS AB Dendritic cells (DCs) are professional antigen-presenting cells which both initiate adaptive immune responses and control tolerance to self-antigens. It has been suggested that these different effects on responder cells depend on subsets of DCs arising from either myeloid or lymphoid hematopoietic origins. In this model, CD8 alpha (+) Mac-1(-) DCs are supposed to be of lymphoid while CD8 alpha (-) Mac-1(+) DCs are supposed to be of myeloid origin. Here we summarize our findings that both CD8 alpha (+) and CD8 alpha (-) DCs can arise from clonogenic common myeloid progenitors (CMPs) in both thymus and spleen. Therefore CD8 alpha expression on DCs does not indicate a lymphoid origin and differences among CD8 alpha (+) and CD8 alpha (-) DCs might rather reflect maturation status than ontogeny. On the basis of transplantation studies, it seems likely that most of the DCs in secondary lymphoid organs and a substantial fraction of thymic DCs are myeloid-derived. C1 Stanford Univ, Sch Med, Beckman Ctr B261, Dept Pathol & Dev Biol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Manz, MG (reprint author), Stanford Univ, Sch Med, Beckman Ctr B261, Dept Pathol & Dev Biol, 279 Campus Dr, Stanford, CA 94305 USA. RI Manz, Markus/C-7588-2011 FU NCI NIH HHS [CA42551]; NIAID NIH HHS [5T32 AI-07290] NR 25 TC 36 Z9 37 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-295-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 938 BP 167 EP 174 PG 8 WC Cell Biology; Multidisciplinary Sciences SC Cell Biology; Science & Technology - Other Topics GA BT12U UT WOS:000172028500019 PM 11458504 ER PT J AU El-Serag, HB Mason, AC Key, C AF El-Serag, HB Mason, AC Key, C TI Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States SO HEPATOLOGY LA English DT Article AB The recent increase in the incidence of hepatocellular cancer in the United States is thought to underlie the rising mortality of this malignancy. However, it remains unknown whether survival of patients with hepatocellular carcinoma (HCC) has changed during the same time period. Using the SEER database (Surveillance, Epidemiology, and End Results) of the National Cancer Institute, we examined the temporal changes and determinants of survival among patients with histologically proven HCC over a 20-year period. Between 1977 and 1996, 7,389 patients diagnosed with HCC were followed in the survival database of SEER, The overall 1-year relative survival rate increased from 14% (95% confidence intervals (CI): 12-16) during 1977-1981 to 23% (95% CI: 21-24) during 1992 to 1996. Between the same two time periods, less improvement was seen in the S-year survival rates, which increased from 2% (95% CI: 1-3) to only 5% (95% CI: 4-7), The median survival increased slightly from 0.57 years during 1977 to 1981 to 0.64 years during 1992 to 1996, In general, there were no significant differences in survival between men and women or between ethnic groups. During 1987 to 1991, a small fraction (0.8%) of patients underwent radical surgery; these patients had 1-year survival of 59% (95% CI: 35-83%), and 5-year survival of 35% (95% CI: 12-58%). Similar rates were seen during 1992-1996. In conclusion, a small improvement in survival of patients with HCC was seen between 1977 and 1996. Most of this apparent benefit is restricted to the first year following cancer diagnosis, raising the possibility of lead-time bias. There were no significant differences related to gender or ethnicity. C1 Houston VA Med Ctr, Gastroenterol Sect, Houston, TX 77211 USA. Houston VA Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Albuquerque Vet Affairs Med Ctr, Albuquerque, NM USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ New Mexico Hosp, Albuquerque, NM USA. RP El-Serag, HB (reprint author), Houston VA Med Ctr, Gastroenterol Sect, 152,2002 Holcombe Blvd, Houston, TX 77211 USA. NR 12 TC 267 Z9 276 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2001 VL 33 IS 1 BP 62 EP 65 DI 10.1053/jhep.2001.21041 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 387BV UT WOS:000166101000009 PM 11124821 ER PT J AU Pitman, RK AF Pitman, RK TI Hippocampal diminution in PTSD: More (or less?) than meets the eye SO HIPPOCAMPUS LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Pitman, RK (reprint author), MGH E, PTSD Res Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 11 TC 36 Z9 36 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 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 2 BP 73 EP 74 DI 10.1002/hipo.1022 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 425QP UT WOS:000168303000001 PM 11345126 ER PT J AU Stern, CE Sherman, SJ Kirchhoff, BA Hasselmo, ME AF Stern, CE Sherman, SJ Kirchhoff, BA Hasselmo, ME TI Medial temporal and prefrontal contributions to working memory tasks with novel and familiar stimuli SO HIPPOCAMPUS LA English DT Article DE hippocampus; parahippocampal gyrus; entorhinal cortex; stimulus matching; delayed-match-to-sample ID SHORT-TERM-MEMORY; RHINAL CORTEX ABLATIONS; LATERAL FRONTAL-CORTEX; NONMATCHING-TO-SAMPLE; LAYER II NEURONS; HIPPOCAMPAL-FORMATION; RECOGNITION MEMORY; ENTORHINAL CORTEX; PLACE MEMORY; MONKEYS AB Lesions of parahippocampal structures impair performance of delayed matching tasks in nonhuman primates, suggesting a role for these structures in the maintenance of items in working memory and short-term stimulus matching. However, most human functional imaging studies have not shown medial temporal activation during working memory tasks and have primarily focused on functional magnetic resonance imaging (fMRI) signal intensity changes in the prefrontal and posterior parietal cortex. The goal of this study was to test the hypothesis that the difference between the human and nonhuman primate data results from the use of highly familiar stimuli in human working memory studies and trial-unique stimuli in nonhuman primate studies. We used fMRI to examine prefrontal and temporal lobe activation during performance of a working memory (two-back) task, using blocks of novel and highly familiar complex pictures. Performance of the working memory task with novel complex pictures resulted in greater signal change within medial temporal lobe structures than performance of the task with familiar complex pictures. In contrast, the working memory task with highly familiar stimuli resulted in greater prefrontal activation. These results are consistent without hypothesis that the medial temporal lobe is recruited for the shortterm maintenance of information that has no prior representation in the brain, whereas the prefrontal cortex is important for monitoring familiar stimuli that have a high degree of interference. A second set of tasks examined stimulus matching. Subjects performed a target-matching task, during which they identified a single target presented in blocks of novel or familiar stimuli. The results provide evidence of hippocampal and parahippocampal recruitment in the target-matching task with familiar stimuli. These results are consistent with prior animal studies and suggest that prefrontal regions may be important for the monitoring and matching of familiar stimuli which have a high potential for interference, whereas medial temporal regions may become proportionally more important for matching and maintenance of novel stimuli. Hippocampus 2001;11: 337-346. (C) 2001 Wiley-Liss, Inc. C1 Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RP Stern, CE (reprint author), Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. EM chantal@bu.edu OI Hasselmo, Michael/0000-0002-9925-6377 FU NINDS NIH HHS [R01 NS41636] NR 54 TC 151 Z9 154 U1 1 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 4 BP 337 EP 346 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 465QR UT WOS:000170601900001 PM 11530838 ER PT J AU Kensinger, EA Ullman, MT Corkin, S AF Kensinger, EA Ullman, MT Corkin, S TI Bilateral medial temporal lobe damage does not affect lexical or grammatical processing: Evidence from amnesic patient HM SO HIPPOCAMPUS LA English DT Article DE lexicon; grammar; language; global amnesia; longitudinal; declarative memory ID ALZHEIMERS-DISEASE; SEMANTIC MEMORY; BRAIN POTENTIALS; HIPPOCAMPAL-FORMATION; DOUBLE DISSOCIATION; DECLARATIVE MEMORY; LANGUAGE; SYSTEM; COMPREHENSION; LOCALIZATION AB In the most extensive investigation to date of language in global amnesia, we acquired data from experimental measures and examined longitudinal data from standardized tests, to determine whether language function was preserved in the amnesic patient H.M. The experimental measures indicated that H.M. performed normally on tests of lexical memory and grammatical function, relative to age- and education-matched control participants. Longitudinal data from four Wechsler subtests (information, Comprehension, Similarities, and Vocabulary), that H.M. had taken 20 times between 1953 (preoperatively) and 2000, indicated consistent performance across time, and provided no evidence of a lexical memory decrement. We conclude that medial temporal lobe structures are not critical for retention and use of already acquired lexical information or for grammatical processing. They are, however, required for acquisition of lexical information, as evidenced in previous studies revealing H.M.'s profound impairment at learning new words. Hippocampus 2001;11:347-360. (C) 2001 Wiley-Liss, Inc. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Georgetown Univ, Dept Neurosci, Washington, DC USA. Georgetown Univ, Dept Linguist, Washington, DC USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. RP Kensinger, EA (reprint author), MIT, Dept Brain & Cognit Sci, E18-470,77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NCRR NIH HHS [RR00088]; NIA NIH HHS [AG 08812, AG 05134]; NIMH NIH HHS [MH-58189] NR 76 TC 42 Z9 43 U1 2 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 4 BP 347 EP 360 DI 10.1002/hipo.1049 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 465QR UT WOS:000170601900002 PM 11530839 ER PT J AU Greene, R Benes, FM Heckers, S Lisman, J AF Greene, R Benes, FM Heckers, S Lisman, J TI Special issue on schizophrenia - Introduction SO HIPPOCAMPUS LA English DT Editorial Material C1 VAMC, Dept Psychiat, Brockton, MA 02401 USA. McLean Hosp, Struct Neurosci Lab, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Brandeis Univ, Dept Biol, Waltham, MA 02254 USA. RP Greene, R (reprint author), VAMC, Dept Psychiat, Brockton, MA 02401 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 3 TC 2 Z9 2 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 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 5 BP 480 EP 481 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 489WN UT WOS:000172015600002 ER PT J AU Heckers, S AF Heckers, S TI Neuroimaging studies of the hippocampus in schizophrenia SO HIPPOCAMPUS LA English DT Article DE hippocampal volume; hippocampal function; blood flow; memory ID MAGNETIC-RESONANCE SPECTROSCOPY; CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; MEDIAL TEMPORAL-LOBE; FIRST-EPISODE; PARAHIPPOCAMPAL GYRUS; LIMBIC SYSTEM; CONSCIOUS RECOLLECTION; ONSET SCHIZOPHRENIA; VOLUME REDUCTION AB Three neuroimaging techniques, morphometric neuroimaging, magnetic resonance spectroscopy, and functional neuroimaging, have provided evidence for abnormal hippocampal structure and function in schizophrenia. Hippocampal volume reduction is now one of the most consistent structural abnormalities found in schizophrenia: it is present at the onset of the illness and, to a lesser degree, in first-degree relatives of schizophrenic probands. Decreased levels of N-acetyl-aspartate point towards a cellular basis of such volume changes. Functional neuroimaging studies have demonstrated abnormal levels of hippocampal activity at rest, during the experience of auditory hallucinations, and during the performance of memory retrieval tasks. These results of neuroimaging studies complement evidence from post-mortem and behavioral studies, which have found regionally specific abnormalities of the hippocampus and of memory function in schizophrenia. (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp East, Dept Psychiat, CNY-9132,Bldg 149,13th St, Cambridge, MA 02139 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 89 TC 242 Z9 244 U1 7 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 5 BP 520 EP 528 DI 10.1002/hipo.1068 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 489WN UT WOS:000172015600006 PM 11732705 ER PT B AU Pardee, AB Ford, HL Biswas, DK Martin, KJ Sager, R AF Pardee, AB Ford, HL Biswas, DK Martin, KJ Sager, R BE Li, JJ Li, SA Daling, JR TI Expression genetics of hormone dependent human tumors SO HORMONAL CARCINOGENESIS III LA English DT Proceedings Paper CT 3rd International Symposium on Hormonal Carcinogenesis CY SEP 06-12, 1998 CL SEATTLE, WA SP NICHHD, Off Res Womens Hlth, Hoechst Mar Roussel, Seattle Breast Canc Res Program, Fred Hutchinson Canc Res Ctr, NCI, NCI, Div Canc Biol, NCI, Div Canc Control & Populat Sci, Wyeth-Ayerst Res, NIEHS, Int Program, NIEHS ID DIFFERENTIAL DISPLAY; ESTROGEN-RECEPTOR; BREAST; CANCER; RNA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-95127-X PY 2001 BP 37 EP 43 PG 7 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA BR54V UT WOS:000166740700004 ER PT J AU Rivolta, C Berson, EL Dryja, TP AF Rivolta, C Berson, EL Dryja, TP TI Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX SO HUMAN MUTATION LA English DT Article DE congenital retinal blindness; Leber congenital amaurosis; LCA1; cone-rod degeneration; CORD; retinitis pigmentosa; RP; CRX; transcription factor; homeobox gene; inherited retinopathy ID HOMEOBOX GENE CRX; RPE65 GENE; MUTATIONS; PHOTORECEPTOR; HOMEODOMAIN; EXPRESSION; DYSTROPHY; SYSTEM AB We summarize 18 mutations in the human CRX gene that have been associated with Leber congenital amaurosis (congenital retinal blindness), cone,rod degeneration, or retinitis pigmentosa. Except for one obviously null allele not definitely associated with a phenotype (a frameshift in codon 9), all CRX mutations appear to be completely penetrant and cause disease in heterozygotes. These dominant alleles fall into two categories. In one group are missense mutations and short, in-frame deletions; in the second group are frameshift mutations, all of which are in the last exon. All of these dominant mutations are likely to produce stable mRNA that is translated. Mutations in the missense group preferentially affect the conserved homeobox (codons 39-98), and all frameshift mutations leave the homeodomain intact but alter the OTX motif encoded by codons 284-295 at the carboxy terminus. We could not uncover any correlation between type of disease (congenital amaurosis vs. cone,rod degeneration or retinitis pigmentosa) and the type of mutation (missense vs. frameshift). Four of the 18 mutations (similar to 20%) were de novo mutations, and all of these were found in isolate cases of Leber congenital amaurosis. Dominant CRX mutations have not been associated with mental retardation or developmental delay that has sometimes been found in Leber congenital amaurosis caused by other genes. Implications regarding potential future therapies are discussed. Hum Mutat 18:488-498, 2001. (C) 2001 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY00169, EY08683] NR 46 TC 50 Z9 52 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2001 VL 18 IS 6 BP 488 EP 498 DI 10.1002/humu.1226 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 497TU UT WOS:000172472200003 PM 11748842 ER PT J AU Black, HR Elliott, WJ Neaton, JD Grandits, G Grambsch, P Grimm, RH Hansson, L Lacouciere, Y Muller, J Sleight, P Weber, MA White, WB Williams, G Wittes, J Zanchetti, A Fakouhi, TD Anders, RJ AF Black, HR Elliott, WJ Neaton, JD Grandits, G Grambsch, P Grimm, RH Hansson, L Lacouciere, Y Muller, J Sleight, P Weber, MA White, WB Williams, G Wittes, J Zanchetti, A Fakouhi, TD Anders, RJ CA CONVINCE Res Grp TI Baseline characteristics and early blood pressure control in the CONVINCE trial SO HYPERTENSION LA English DT Article DE clinical trials; verapamil; atenolol; hydrochlorothiazide ID ISOLATED SYSTOLIC HYPERTENSION; ANTIHYPERTENSIVE DRUGS; MILD HYPERTENSION; ACTIVE TREATMENT; PREVALENCE; POPULATION; LIFE; RATIONALE; AWARENESS; PLACEBO AB Blood pressure (BP) control rates around the world are suboptimal, Part 2 of the National Health and Nutrition Educational Survey (NHANES) III indicates that only 27.4% of hypertensive Americans aged 18 to 74 years have a BP of <140/90 mm Hg, We wanted to assess BP control during the first 2 years and to describe the baseline characteristics of patients enrolled in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Study, an international clinical trial that compares outcomes in hypertensive patients randomized to initial treatment with either controlled-onset extended-release verapamil or the investigator's choice of atenolol or hydrochlorothiazide. At randomization, BP was <140/90 mm Hg in only 20.3% of the 16 602 subjects (average+/-SD age 65.6+/-7.4 years; 56% women, 84% white/7% black/7% Hispanic). The average BP at enrollment was 148/85 mm Hg for patients taking BP medications (n=13 879) and 161/94 mm Hg for previously untreated patients (n=2723). After medication titration, with a transtelephonic computer that recommended an increase in the dose or number of antihypertensive agents whenever the BP was 140/90 mm Hg, 84.8% of the subjects attained the goal BP, During 2 years of treatment, BP control was maintained in 67% to 69% of the subjects (69% to 71% for systolic BP of <140 mm Hg and 90% for diastolic BP of <90 mm Hg). These data suggest that the control of systolic BP is more difficult than the control of diastolic BP. The US national goal of having 50% of hypertensives with a BP of <140/90 mm Hg may be achievable if a forced titration strategy is used. Interested investigators, free care and medications, and well-educated subjects may make the attainment of such a goal easier in the CONVINCE study than in the general population. C1 Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. Univ Minnesota, Div Biostat, Minneapolis, MN USA. Uppsala Univ, Dept Geriatr, Uppsala, Sweden. CHU Quebec, Quebec City, PQ, Canada. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England. Univ Oxford, Dept Med, Oxford OX3 9DU, England. Brookdale Hosp, Dept Med, Brooklyn, NY USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Univ Connecticut, Sch Med, Dept Med, Sect Hypertens & Clin Pharmacol, Farmington, CT USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Stat Collaborat, Washington, DC USA. Univ Milan, Milan, Italy. Osped Maggiore, Milan, Italy. Ctr Auxol Italiano, Milan, Italy. Searle Labs, Clin Res, Skokie, IL USA. RP Black, HR (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, 1700 W Van Buren St,Suite 470, Chicago, IL 60612 USA. RI Petr, Petr/I-9423-2014 NR 33 TC 94 Z9 102 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2001 VL 37 IS 1 BP 12 EP 18 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 394MM UT WOS:000166527900003 ER PT J AU Solo, V Purdon, P Weisskoff, R Brown, E AF Solo, V Purdon, P Weisskoff, R Brown, E TI A signal estimation approach to functional MRI SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE functional MRI; image processing; inverse problem; MRI ID SENSORY STIMULATION AB In the last half decade, fast methods of magnetic resonance imaging have led to the possibility, for the first time, of noninvasive dynamic brain imaging. This has led to an explosion of work in the Neurosciences. From a signal processing viewpoint the problems are those of nonlinear spatio-temporal system identification, In this paper, we develop new methods of identification using novel spatial regularization, We also develop a new model comparison technique and use that to compare our method with existing techniques on some experimental data. C1 Univ New S Wales, Sch Elect Engn & Telecommun, Sydney, NSW 2052, Australia. Harvard Univ, Sch Med, Dept Radiol, MGH NMR Ctr, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Neurosci Stat Res Lab, Dept Anaesthesia & Crit Care, Cambridge, MA 02138 USA. RP Univ New S Wales, Sch Elect Engn & Telecommun, Sydney, NSW 2052, Australia. FU NCRR NIH HHS [P41RR14075] NR 25 TC 29 Z9 29 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JAN PY 2001 VL 20 IS 1 BP 26 EP 35 DI 10.1109/42.906422 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 408KG UT WOS:000167324900003 PM 11293689 ER PT J AU Fischl, B Liu, A Dale, AM AF Fischl, B Liu, A Dale, AM TI Automated manifold surgery: Constructing geometrically accurate and topologically correct models of the human cerebral cortex SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE human cerebral cortex; topology; segmentation ID HUMAN VISUAL-CORTEX; POSITRON-EMISSION TOMOGRAPHY; SURFACE-BASED ANALYSIS; FUNCTIONAL MRI; CORTICAL SURFACE; HUMAN BRAIN; COORDINATE SYSTEM; RETINOTOPIC ORGANIZATION; AREAS; RECONSTRUCTION AB Highly accurate surface models of the cerebral cortex are becoming increasingly important as tools in the investigation of the functional organization of the human brain. The construction of such models is difficult using current neuroimaging technology due to the high degree of cortical folding. Even single voxel misclassifications can result in erroneous connections being created between adjacent hanks of a sulcus, resulting in a topologically inaccurate model. These topological defects cause the cortical model to no longer be homeomorphic to a sheet, preventing the accurate inflation, flattening, or spherical morphing of the reconstructed cortex. Surface deformation techniques can guarantee the topological correctness of a model, but are time-consuming and may result in geometrically inaccurate models. in order to address this need we have developed a technique for taking a model of the cortex, detecting and fixing the topological defects while leaving that majority of the model intact, resulting in a surface that is both geometrically accurate and topologically correct. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Fischl, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM fischl@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41-RR14075, R01-RR13609]; NINDS NIH HHS [R01-NS39581] NR 51 TC 722 Z9 729 U1 1 U2 13 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JAN PY 2001 VL 20 IS 1 BP 70 EP 80 DI 10.1109/42.906426 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 408KG UT WOS:000167324900007 PM 11293693 ER PT J AU de Alboran, IM O'Hagan, RC Gartner, F Malynn, B Davidson, L Rickert, R Rajewsky, K DePinho, RA Alt, FW AF de Alboran, IM O'Hagan, RC Gartner, F Malynn, B Davidson, L Rickert, R Rajewsky, K DePinho, RA Alt, FW TI Analysis of C-MYC function in normal cells via conditional gene-targeted mutation SO IMMUNITY LA English DT Article ID EXPRESSION INDUCES APOPTOSIS; B-CELLS; TRANSGENIC MICE; GROWTH ARREST; CYCLE PROGRESSION; PROTEIN-SYNTHESIS; ANTIGEN RECEPTOR; T-CELLS; IN-VIVO; FIBROBLASTS AB Germline inactivation of c-myc in mice causes embryonic lethality. Therefore, we developed a LoxP/Cre-based conditional mutation approach to test the role of c-myc in mouse embryonic fibroblasts (MEFs) and mature B lymphocytes. Cre expression resulted in reduced proliferation of wild-type MEFs, but c-Myc-deficient MEFs showed a further reduction. In contrast to fibroblasts, Cre expression had no apparent affect on wild-type B cell proliferation. Deletion of both c-Myc genes in B cells led to severely impaired proliferation in response to anti-CD40 plus IL-4. However, treated cells did upregulate several early activation markers but not CD95 or CD95 ligand. We discuss these findings with respect to potential c-Myc functions in proliferation and apoptosis and also discuss potential limitations in the Cre-mediated gene inactivation approach. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. Univ Cologne, Inst Genet, D-50931 Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RI Gartner, Fatima/A-3530-2010 OI Gartner, Fatima/0000-0002-5302-0086 FU NCI NIH HHS [CA61009]; NEI NIH HHS [EY09300]; NICHD NIH HHS [HD28317] NR 60 TC 233 Z9 237 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2001 VL 14 IS 1 BP 45 EP 55 DI 10.1016/S1074-7613(01)00088-7 PG 11 WC Immunology SC Immunology GA 394FQ UT WOS:000166513800005 PM 11163229 ER PT J AU Anderson, B AF Anderson, B TI g as a consequence of shared genes SO INTELLIGENCE LA English DT Article DE intelligence; genetics; evolution; mutation; g factor ID INTELLIGENCE AB This article argues that g can arise from the effect of shared genes influencing cognitive test performance. Further, the puzzling effect that intercorrelations between cognitive tests are higher at lower ability levels can be accounted for by incorporating the concept of deleterious mutation load. Population genetics holds that one of the determinants of retained genetic variation is deleterious mutation load, and as mutations increase genetic variation, the effect is to yield intercorrelation magnitudes that are inversely correlated to performance. A simple mathematical demonstration of how this occurs is provided. This argument predicts the need for a profound shift of tactics in the search for biological bases of g. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Alabama, Neurol Serv 127, Dept Neurol, Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Anderson, B (reprint author), Brown Univ, Brain Sci Program, Box 1953, Providence, RI 02912 USA. NR 12 TC 8 Z9 8 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0160-2896 J9 INTELLIGENCE JI Intelligence PY 2001 VL 29 IS 5 BP 367 EP 371 DI 10.1016/S0160-2896(01)00069-1 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 468WC UT WOS:000170780300001 ER PT J AU Kacmarek, RM AF Kacmarek, RM TI Partial liquid ventilation: is there a niche? SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS SYNDROME; END-EXPIRATORY PRESSURE; GAS-EXCHANGE; LUNG INJURY; IMPROVEMENT; FAILURE; MODEL C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02115 USA. RP Kacmarek, RM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02115 USA. NR 16 TC 0 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JAN PY 2001 VL 27 IS 1 BP 1 EP 2 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 400XJ UT WOS:000166897700001 PM 11280618 ER PT J AU Holzmann, A Manktelow, C Weimann, J Bloch, KD Zapol, WM AF Holzmann, A Manktelow, C Weimann, J Bloch, KD Zapol, WM TI Inhibition of lung phosphodiesterase improves responsiveness to inhaled nitric oxide in isolated-perfused lungs from rats challenged with endotoxin SO INTENSIVE CARE MEDICINE LA English DT Article DE nitric oxide; hyporesponsiveness; phosphodiesterase; isolated perfused lung ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; PERSISTENT PULMONARY-HYPERTENSION; CGMP-SPECIFIC PHOSPHODIESTERASE; RESPIRATORY-DISTRESS-SYNDROME; IDENTIFICATION; EXPRESSION; GENE; OXYGENATION; INHALATION; HYDROLYZES AB Objectives:To investigate the ability of phosphodiesterase (PDE) selective inhibitors to improve responsiveness to inhaled nitric oxide (NO) in isolated-perfused lungs of rats pretreated with endotoxin/lipopolysaccharide (LPS). Design and setting: Prospective, controlled animal study in the animal research facility of a university hospital. Interventions: Sixteen hours after adult Sprague-Dawley rats were injected intraperitoneally with 0.4 mg/ kg E. coli 0111:B4 LPS administration, lungs were isolated and perfused, and the thromboxane mimetic U46619 was employed to increase the mean pulmonary artery pressure by 5-7 mmHg. The lungs were then ventilated with or without 0.4 ppm NO, and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; PDE type 2 inhibitor), milrinone (PDE type 3 inhibitor), or zaprinast (inhibitor of PDE types 5 and 9) were added to the perfusate. Measurements and results: In the presence of EHNA (12.5, 25, 50 muM) the vasodilator response to inhaled NO was not greater than in its absence (0.25 +/- 0.25, 0.5 +/- 0.25, 0.75 +/- 0.25 mmHg vs. 0.25 +/- 0.25, 0.5 +/- 0.25, 0.75 +/- 0.25 mmHg, re spectively). In the presence of milrinone (125, 250, 500 nM), the vasodilator response to inhaled NO was also not improved. In contrast, zaprinast (3.7, 7.4, 14.8 muM) augmented the pulmonary vasodilatory effect of inhaled NO in lungs from LPS-pretreated rats from 0.25 +/- 0.25, 0.5 +/- 0.25, 0.75 +/- 0.25 mmHg to 0.75 +/- 0.25, 1.5 +/- 0.5, 1.75 +/- 0.75 mmHg, respectively (p < 0.05). Conclusions: Our results demonstrate that inhibition of pulmonary PDE enzyme activity with zaprinast increases vasodilator responsiveness to inhaled NO in lungs obtained from rats 16 h after LPS challenge. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Univ Heidelberg, Dept Anaesthesiol, D-69120 Heidelberg, Germany. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bloch, KD (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-55377, HL-42397] NR 34 TC 16 Z9 16 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JAN PY 2001 VL 27 IS 1 BP 251 EP 257 DI 10.1007/s001340000774 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 400XJ UT WOS:000166897700038 PM 11280644 ER PT J AU Lin, HM Martelli, MP Bierer, BE AF Lin, HM Martelli, MP Bierer, BE TI The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE Crk; NF-AT; phosphatidylinositol-3 kinase; signal transduction; Syk; T lymphocytes; ZAP-70 ID PHOSPHOTYROSINE-BINDING DOMAIN; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE-ACTIVITY; NEGATIVE REGULATOR; INTERLEUKIN-2 PROMOTER; PROTOONCOGENE PRODUCT; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; JURKAT CELLS; CD2 AB The CD2 co-receptor expressed on the surface of T lymphocytes is able to stimulate T cell activation, proliferation and cytokine production in the absence of direct engagement of the antigen-specific TCR, Engagement of human CD2 by mitogenic pairs of anti-CDP mAb induces tyrosine phosphorylation of a number of intracellular proteins including a 120 kDa phosphoprotein that we identify as the proto-oncogene c-Cbl, Rapidly tyrosine phosphorylated following stimulation of a number of cell surface receptors, c-Cbl is an adaptor protein that has been shown to associate with a complex of intracellular signaling molecules, and to mediate both positive and negative regulatory effects. Here we show that, like TCR-CD3 stimulation, stimulation of CD2 enhanced the association of c-Cbl with both Crk(L) and the p85 subunit of phosphatidylinositol-3 kinase, Overexpression of wild-type c-Cbl protein inhibited both CD2- and CD3-induced NF-AT transcriptional activity, suggesting that CD2 signaling is also negatively regulated by c-Cbl, The inhibitory effect of c-Cbl depended upon its N-terminal phosphotyrosine-binding domain, the domain that has been shown to be required for inhibition of the Syk/ZAP-70 family kinases. In Syk(-) Jurkat T cells stably expressing wild-type ZAP-70, CD2 stimulation induced only a minimal increase in ZAP-70 tyrosine phosphorylation. Nevertheless, ZAP-70 kinase was required for CDS-mediated NF-AT transcriptional activity. Thus, CDS-mediated NF-AT transcriptional activity appears to depend upon ZAP-70/Syk kinases and to be negatively regulated by c-Cbl. C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, Lab Lymphocyte Biol, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. RI Martelli, Maria Paola/I-5618-2012 NR 68 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 2001 VL 13 IS 1 BP 13 EP 22 DI 10.1093/intimm/13.1.13 PG 10 WC Immunology SC Immunology GA 394ZU UT WOS:000166554900003 PM 11133830 ER PT J AU Scully, R Young, RH AF Scully, R Young, RH TI A half century in gynecological pathology: Reminiscences of Robert E. Scully on his career - An interview with Robert H. Young SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Editorial Material ID YOLK-SAC TUMOR; CLINICOPATHOLOGICAL ANALYSIS; BORDERLINE MALIGNANCY; OVARY; ADENOCARCINOMA; DIFFERENTIATION; CARCINOMA; UTERUS; VAGINA C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Scully, R (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. NR 72 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2001 VL 20 IS 1 BP 2 EP 15 PG 14 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 388JP UT WOS:000166177600002 PM 11192070 ER PT J AU Hurwitz, MD Kaplan, ID Svensson, GK Hynynen, K Hansen, MS AF Hurwitz, MD Kaplan, ID Svensson, GK Hynynen, K Hansen, MS TI Feasibility and patient tolerance of a novel transrectal ultrasound hyperthermia system for treatment of prostate cancer SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE hyperthermia; prostate cancer; radiation ID THERAPY-ONCOLOGY-GROUP; LOCALLY ADVANCED ADENOCARCINOMA; RADIATION-THERAPY; PHASE-I/II; RADIOTHERAPY; TUMORS; GOSERELIN; CARCINOMA; TRIAL AB This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4(th) edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T-50) was 40.8 degreesC and mean CEM T-90=43 degreesC was 3.4 min. Rectal wall temperature was maintained at less than or equal to 40 degreesC. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a 'New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCl common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/- hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Hurwitz, MD (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [CA 31303] NR 10 TC 22 Z9 22 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD JAN PY 2001 VL 17 IS 1 BP 31 EP 37 DI 10.1080/02656730150201570 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 382UN UT WOS:000165844300003 PM 11212878 ER PT J AU Teichner, G Horner, MD Harvey, RT AF Teichner, G Horner, MD Harvey, RT TI Neuropsychological predictors of the attainment of treatment objectives in substance abuse patients SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE adults; drug use; alcohol use; substance abuse; neuropsychological impairment; cognition; treatment outcome ID MEN ALCOHOLICS; COCAINE; RELAPSE; DYSFUNCTION; ACQUISITION; PERSONALITY; IMPAIRMENT; LENGTH; MEMORY; STAY AB This study examined the: contribution of neuropsychological functioning to the attainment of treatment objectives in substance abuse patients. Subjects were 85 patients enrolled in comprehensive, inpatient and outpatient substance abuse treatment at 3 VA Medical Center. Most subjects were diagnosed with Alcohol Dependence or Abuse. and nearly half were seeking treatment for Cocaine Dependence or Abuse. After acute detoxification, but before beginning individualized treatment, subjects were administered a neuropsychological screening battery to assess cognitive functioning and affective status. They then attended a variety of daily group therapies. Each therapy group had its own set of specific treatment objectives. on each treatment day, group therapists rated each patient's attainment of the specific objectives for their group. Groups included Assertiveness Training (Levels I and II). Stress Management (Levels I and II). Social Skills Training. Job Skills. Relapse Prevention (Levels I and II). Leisure Planning. Leisure Skills, Occupational Therapy, and 12-Step Study. Stepwise multiple regression indicated that the best predictors of overall objective attainment were better attention (WMS-R Digits Backwards) and less depressive symptomatology (Beck Depression Inventor?;). These results suggest that attention and mood have a modest yet significant impact on the success of treatment interventions for substance abuse patients. Thus, evaluation of cognitive as well as affective factors in substance abuse patients might be helpful in designing and implementing specialized interventions to maximize the likelihood of treatment success. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC USA. RP Teichner, G (reprint author), Med Univ S Carolina, 96 Jonathan Lucas St,Suite 124,POB 250626, Charleston, SC 29425 USA. RI Reis, Aline/G-9573-2012 NR 36 TC 46 Z9 47 U1 1 U2 4 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 0020-7454 J9 INT J NEUROSCI JI Int. J. Neurosci. PY 2001 VL 106 IS 3-4 BP 253 EP 263 DI 10.3109/00207450109149753 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 420MQ UT WOS:000168009100011 PM 11264924 ER PT J AU Iosifescu, DV Nierenberg, AA Howarth, S Worthington, JJ Alpert, JE Fava, M AF Iosifescu, DV Nierenberg, AA Howarth, S Worthington, JJ Alpert, JE Fava, M TI T3 blood levels and treatment outcome in depression SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-of-Medicine-and-Psychiatry CY NOV 16, 1999 CL NEW ORLEANS, LOUISIANA SP Assoc Med & Psychiat DE thyroid hormones; triiodothyronine; T-3-RU; major depression; treatment response; antidepressant ID TREATMENT-RESISTANT DEPRESSION; PITUITARY-THYROID-AXIS; MAJOR DEPRESSION; HYPERTHYROIDISM; HYPOTHYROIDISM AB Objective: We examined the correlation between the basal triiodothyronine resin uptake (T-3-RU) levels in depressed subjects and the response to antidepressant treatment. Method: We treated with fluoxetine 235 outpatients meeting DSM-IV criteria for major depression. We measured T-3 resin uptake (T-3-RU) levels before the onset of treatment. The 17-item Hamilton Rating Scale for Depression (Ham-D-17) was administered before, during and after the eight weeks of treatment to assess changes in depressive symptoms. Results: 16 patients (6.8 percent) had low T-3-RU levels (range 16.5-21), and 7 patients (3.0 percent) had high T-3-RU levels (range 36-38). No relationship was found between T-3-RU levels and clinical improvement, defined as either total Ham-D-17 score change or Ham-D-17 score less than or equal to 7 in the last 3 weeks of treatment, even after adjusting for baseline severity of depression. Conclusion: Abnormal T-3-RU levels are rather uncommon in outpatient depression and do not correlate with the response to antidepressant treatment or lack thereof. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Iosifescu, DV (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 812, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 11 TC 6 Z9 6 U1 0 U2 1 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2001 VL 31 IS 4 BP 367 EP 373 PG 7 WC Psychiatry SC Psychiatry GA 533LM UT WOS:000174531500002 PM 11949735 ER PT J AU Datta, MW Ulbright, TM Young, RH AF Datta, MW Ulbright, TM Young, RH TI Renal cell carcinoma metastatic to the testis and its adnexa: A report of five cases including three that accounted for the initial clinical presentation SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testis; metastasis; renal cell carcinoma ID CORD-STROMAL TUMORS; TESTICULAR METASTASIS; COLON-CARCINOMA; ADENOCARCINOMA; MANIFESTATION; DISTINCTION; NEOPLASMS AB Five cases of renal cell carcinoma metastatic to the testis or its adnexa are described, including 3 that represented the initial presentation and mimicked primary testicular neoplasms. The patients ranged from 46 to 85 years of age. Three presented with self-identified testicular masses. One patient was investigated because of fever of unknown origin and was found to have a left rib metastasis. Further work-up led to the discovery of a testicular mass. The final patient had a tumor of the spermatic cord that was examined without knowledge that he had a Drier renal neoplasm. All the tumors were unilateral. They ranged from 1.8 to 5.0 cm; multiple rumor nodules were present in one of them but the others were discrete solitary masses. Four tumors were yellow/yellow-tan, and one was gray. On microscopic examination all the tumors were of the clear cell type. Patterns included solid sheets, acini, cysts, alveoli, and trabeculae. Two had prominent vascular invasion. Diagnoses initially entertained in these cases included Sertoli cell tumor, Sertoli-Leydig cell tumor, and clear cell cystadenoma of the epididymis. In 3 cases a kidney tumor was discovered 2 to 4 weeks after the diagnosis of renal cell carcinoma metastatic to the testis was rendered. On follow-up two patients died of rumor, and two were alive (5 months and 1 year) after orchiectomy. The diagnosis of renal cell carcinoma metastatic to the testis should be considered in evaluating a clear cell tumor of the testis, particularly in an older male or if the appearance suggests a Sertoli cell tumor. The differences in survival between metastatic renal cell carcinoma and sex cord-stromal tumors indicate the importance of considering the former in the differential. C1 Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. Froedtert Mem Lutheran Hosp, Dept Pathol, Milwaukee, WI USA. Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Datta, MW (reprint author), Med Coll Wisconsin, Dept Pathol, POB 26509, Milwaukee, WI 53226 USA. NR 43 TC 25 Z9 25 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JAN PY 2001 VL 9 IS 1 BP 49 EP 56 DI 10.1177/106689690100900108 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 421HY UT WOS:000168060000006 PM 11469344 ER PT J AU Schaller, SA Li, SG Ngo-Muller, V Han, MJ Omi, M Anderson, R Muneoka, K AF Schaller, SA Li, SG Ngo-Muller, V Han, MJ Omi, M Anderson, R Muneoka, K TI Cell biology of limb patterning SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 203 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review DE limb patterning; embryo development; signaling pathways; morphogenesis ID APICAL ECTODERMAL RIDGE; FIBROBLAST-GROWTH-FACTOR; DEVELOPING CHICK LIMB; T-BOX GENES; HEPARAN-SULFATE PROTEOGLYCAN; BONE MORPHOGENETIC PROTEINS; RETINOIC ACID RECEPTORS; POSITIVE FEEDBACK LOOP; SONIC-HEDGEHOG; VERTEBRATE LIMB C1 Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Inst Cochin Genet Mol, INSRM U129, F-75014 Paris, France. RP Schaller, SA (reprint author), Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA. NR 208 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2001 VL 203 BP 483 EP 517 PG 35 WC Cell Biology SC Cell Biology GA BR61J UT WOS:000166954200012 PM 11131524 ER PT J AU Rajdev, L Yu, ZF Wadler, S Weller, E Kahn, SB Tormey, D Skeel, R Wiernik, PH AF Rajdev, L Yu, ZF Wadler, S Weller, E Kahn, SB Tormey, D Skeel, R Wiernik, PH TI N-Methylformamide in advanced squamous cancer of the uterine cervix: An Eastern Cooperative Oncology Group phase II trial SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE N-Methylformamide; squamous cell carcinoma; uterine cervix ID HYBRID POLAR COMPOUNDS; TRANS-RETINOIC ACID; RANDOMIZED TRIAL; CELL CARCINOMA; DIFFERENTIATION AB Purpose: Preclinical and clinical data support the study of polar-planar compounds such as N-Methylformamide (NMF) in advanced squamous cell carcinoma of the uterine cervix (SCC). This phase II trial sought to determine the efficacy and toxicities of NMF in patients with advanced SCC. Patients and methods: Eligibility for this trial required bidimensionally measurable squamous or adenosquamous cell cancer of the uterine cervix incurable by surgery or radiation therapy, ECOG performance status of less than or equal to2, no prior NMF and no more than one prior chemotherapy regimen. Patients received NMF at 2000 mg/m(2) intravenously over 15-30 minutes days 1, 8 and 15. The cycle was repeated every 42 days. A single dose escalation of 25%, 500 mg/m(2) was made after the first cycle if the toxicities did not exceed grade I for hepatic toxicity and grade II for nausea and vomiting. Results: From July 1987 through September 1998, 21 patients with advanced squamous cell carcinoma of the uterine cervix were entered on study. Two patients were ineligible because there was no pretreatment SGOT on one and the other deteriorated prior to drug approval. Therefore, 19 patients were include in the analysis of response and survival. Four were inevaluable, 3 due to inappropriate tumor evaluation and I secondary to grade III vomiting, who went off study. These patients were included in the denominator while computing the results. There were 2 deaths, one due to pulmonary hemorrhage from perforation during central venous insertion and one due to disease. 30% (6/19) patients had toxicities, Eastern Cooperative Oncology Group (ECOG) grade III or higher and 2 of these patients suffered multiple grade III toxicities. There were no complete or partial responses. Conclusion: In this population, NMF in the dose and schedule employed exhibited no clinical activity. C1 Albert Einstein Canc Ctr, Bronx, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MCP Hahnemann Univ, Philadelphia, PA USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Med Coll Ohio, Toledo, OH 43699 USA. New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY USA. RP Rajdev, L (reprint author), 1825 Eastchester Rd,Room 2 S 63, Bronx, NY 10461 USA. FU NCI NIH HHS [CA 66636, CA 21076, CA 23318, CA 14958, CA 21115] NR 22 TC 2 Z9 3 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PY 2001 VL 19 IS 3 BP 233 EP 237 DI 10.1023/A:1010672618269 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 457XY UT WOS:000170164000005 PM 11561680 ER PT J AU Brooks, SE Gu, XL Samuel, S Marcus, DM Bartoli, M Huang, PL Caldwell, RB AF Brooks, SE Gu, XL Samuel, S Marcus, DM Bartoli, M Huang, PL Caldwell, RB TI Reduced severity of oxygen-induced retinopathy in eNOS-deficient mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 00-MAY 02, 2000 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL GROWTH-FACTOR; ISCHEMIA-REPERFUSION INJURY; FOCAL CEREBRAL-ISCHEMIA; SUPEROXIDE-DISMUTASE; VITAMIN-E; RETINAL VASCULATURE; VEGF EXPRESSION; ANIMAL-MODEL; RAT RETINA AB PURPOSE. Exposure of premature human infants to hyperoxia results in the obliteration of developing retina capillaries, leading to a vision-threatening retinopathy termed retinopathy of prematurity (ROP). The authors hypothesized that this process may be mediated in part by endothelial nitric oxide (NO)- derived oxidants such as peroxynitrite and tested this hypothesis in a mouse model of ROP. METHODS. Normal mice, mice treated with the nitric oxide synthase (NOS) inhibitor,N-G-nitro-L-arginine (L-NNA), and knockout mice carrying a homozygous targeted disruption of the gene for endothelial NOS (eNOS) were studied in an experimental model of ROP. Retinas were compared for extent of capillary obliteration in hyperoxia, vascular endothelial growth factor (VEGF) expression, nitrotyrosine formation, and vitreous neovascularization. RESULTS. Oxyen-induced retinal vaso-obliteration was significantly: reduced by L-NNA treatment (43% decrease from controls). The eNOS-deficient mice showed a similar reduction in vaso-obliteration (46% decrease from controls), and vitreous neovascularization was also substantially reduced (threefold decrease). Retinal nitrotyrosine formation, a measure of in situ peroxynitrite modification of proteins, was significantly elevated in normal mice during hyperoxia, in a spatial and temporal pattern consistent with a role in oxygen-induced vaso- obliteration. This was not seen in eNOS-deficient mice. VEGF expression was similar in both groups of mice, although suppression in hyperoxia was slightly blunted in eNOS-deficient mice. CONCLUSIONS. These data suggest a role for NO and peroxynitrite in the pathogenesis of ROP. Therapies aimed at modulation of eNOS activity may have therapeutic potential for preventing ROP. C1 Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. Med Coll Georgia, Dept Pediat, Augusta, GA 30912 USA. Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA. Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA. Massachusetts Gen Hosp, Cardiovasc Res Lab, Charlestown, MA USA. RP Brooks, SE (reprint author), Med Coll Georgia, Dept Ophthalmol, 1120 15th St, Augusta, GA 30912 USA. FU NEI NIH HHS [EY04618, EY11766] NR 45 TC 106 Z9 107 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2001 VL 42 IS 1 BP 222 EP 228 PG 7 WC Ophthalmology SC Ophthalmology GA 388CG UT WOS:000166159400033 PM 11133872 ER PT J AU Green, MJ Fong, S Mauger, DT Ubel, PA AF Green, MJ Fong, S Mauger, DT Ubel, PA TI Rationing HIV medications: What do patients and the public think about allocation policies? SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; AIDS; rationing; economics; ethics; health policy ID OREGON HEALTH PLAN; IMMUNODEFICIENCY-VIRUS INFECTION; INTENSIVE-CARE UNIT; AIDS; TRANSPLANTATION; PRIORITIES; SERVICES; EPIDEMIOLOGY; CLINICIAN; PROGRESS AB Background: New medications for treating HIV/AIDS are effective, but expensive, and funding shortfalls have led many state AIDS Drug Assistance Programs (ADAPs) to ration these drugs. Little is known about the views of those most directly affected by rationing policies. This study explores attitudes of patients with HIV and the general public toward specific rationing strategies. Methods: A Likert-style, self-administered questionnaire about rationing expensive HIV medications in the context of a budget shortfall was administered to patients with HIV and shopping mall patrons in central Pennsylvania. Subjects were asked how much they agreed or disagreed with seven drug rationing policies. Results: In all, 100 patients and 101 shoppers completed the sun ey (response rate = 89%). A majority in both groups "strongly" or "somewhat" disagreed with six of the seven rationing policies described, and patients more strongly disagreed with the policies than did the public. The five policies actually used by state ADAPs (first come first serve, limiting expensive medicines, limiting new patient enrollment, giving the expensive medicines to the sickest, using a spending cap) lacked support in either group. Conclusions: HIV drug rationing policies currently in use do not reflect the preferences of patients and the public. Integrating the views of those affected by the rationing decisions would raise difficult challenges to current programs. C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Humanities, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Gen Internal Med Sect, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Hlth Evaluat Sci, Hershey, PA USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Green, MJ (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Humanities, H134,500 Univ Dr, Hershey, PA 17033 USA. RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 49 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD JAN 1 PY 2001 VL 26 IS 1 BP 56 EP 62 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 393YQ UT WOS:000166497600007 PM 11176269 ER PT J AU Gordon, AJ Wentz, CM Gibbon, JL Mason, AD Freyder, PJ O'Toole, TP AF Gordon, AJ Wentz, CM Gibbon, JL Mason, AD Freyder, PJ O'Toole, TP TI Relationships between patient characteristics and unsuccessful substance abuse detoxification SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 29-MAY 01, 1999 CL SAN FRANCISCO, CALIFORNIA SP Soc Gen Internal Med DE substance-related disorders; substance withdrawal syndrome; substance abuse treatment centers ID ALCOHOL-WITHDRAWAL; INPATIENT AB Objective: History and laboratory evaluations are common for patients entering substance abuse detoxification programs. We sought to identify if patient history and laboratory characteristics entering a detoxification program were associated with unsuccessful detoxification. Design: Retrospective cohort study of 186 patients of a residential-inpatient short-term medical detoxification facility. Unsuccessful detoxification was defined as leaving for urgent medical referral or against program advice. Results: Patients were predominantly male, middle-aged, minority unemployed, and poly-substance users. Twenty-four patients (13%) did not complete the detoxification program (4 left for urgent medical referral, 20 left against program advice). Unsuccessful detoxification was associated with nausea and/or vomiting ip = 0.032), Caucasian race = 0.002), and opiates as a drug elf choice (p = 0.018). Laboratory normalities were common but none were associated with unsuccessful detoxification. Conclusions: For patients admitted to a medically monitored detoxification facility, few patient characteristics were associated with detoxification outcome. Routine admission laboratories without clinical correlation may be unwarranted. (C) 2001 by The Haworth Press, Inc. All rights reserved. C1 VA Pittsburgh HealthCare Syst, Gen Internal Med Sect, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Salvat Army Publ Inebriate Program, Pittsburgh, PA USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. RP Gordon, AJ (reprint author), VA Pittsburgh HealthCare Syst, Gen Internal Med Sect, Pittsburgh, PA USA. NR 22 TC 6 Z9 6 U1 2 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2001 VL 20 IS 2 BP 41 EP 53 PG 13 WC Substance Abuse SC Substance Abuse GA 423QT UT WOS:000168188800004 PM 11318396 ER PT J AU Weinrieb, RM Van Horn, DHA McLellan, AT Volpicelli, JR Calarco, JS Lucey, MR AF Weinrieb, RM Van Horn, DHA McLellan, AT Volpicelli, JR Calarco, JS Lucey, MR TI Drinking behavior and motivation for treatment among alcohol-dependent liver transplant candidates SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE alcohol dependence; alcoholism treatment; liver transplant; motivation ID C VIRUS-INFECTION; DISEASE; RISK; PSYCHOTHERAPY; CONSUMPTION; CIRRHOSIS; HISTORY AB Alcohol misuse is the second most common indication for liver transplantation in the United States. Our post-transplant alcoholism treatment trial suggested that current interventions might not he transferable to liver transplantees. We sought to identify differences between patients awaiting liver transplantation and alcoholics entering treatment without severe liver disease. Thirty transplant patients were compared to thirty naltrexone study patients on medical status, alcohol and drug use, alcohol craving, motivation for treatment, psychiatric symptoms, anti psychosocial problems. Lifetime alcohol consumption was greater for transplant patients compared to naltrexone patients. In contrast to the naltrexone group, transplant patients denied craving for alcohol and showed little motivation for alcoholism treatment. Groups did not differ on other psychosocial measures. Liver transplant patients differ from patients in alcoholism treatment trials on measures of alcohol consumption, alcohol craving and motivation for treatment. Alcoholism interventions should accommodate their medical condition and boost motivation for continued abstinence. (C) 2001 by The Haworth Press Inc. All rights reserved. C1 Univ Penn, Hlth Syst, Dept Psychiat, Treatment Res Ctr,Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Horizon Mental Hlth, N Wales, PA USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Weinrieb, RM (reprint author), Univ Penn, Hlth Syst, Dept Psychiat, Treatment Res Ctr,Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIAAA NIH HHS [1R01AA12299-01, R01-AA-07517]; NIDA NIH HHS [DA07705] NR 25 TC 34 Z9 34 U1 1 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2001 VL 20 IS 2 BP 105 EP 119 PG 15 WC Substance Abuse SC Substance Abuse GA 423QT UT WOS:000168188800009 PM 11318394 ER PT J AU Tekirian, TL AF Tekirian, Tina L. TI Commentary: A beta N- Terminal Isoforms: Critical contributors in the course of AD pathophysiology SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Editorial Material C1 [Tekirian, Tina L.] Massachusetts Gen Hosp, Genet & Aging Unit, Boston, MA 02129 USA. [Tekirian, Tina L.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Tekirian, Tina L.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Tekirian, TL (reprint author), Massachusetts Gen Hosp, Genet & Aging Unit, Bldg 149,13th St,Room 6133, Boston, MA 02129 USA. EM tekirian@helix.mgh.harvard.edu NR 59 TC 21 Z9 21 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2001 VL 3 IS 2 BP 241 EP 248 PG 8 WC Neurosciences SC Neurosciences & Neurology GA V23ID UT WOS:000208335600009 ER PT J AU Kellogg, DL Liu, Y Pergola, PE AF Kellogg, DL Liu, Y Pergola, PE TI Genome and Hormones: Gender differences in physiology - Selected contribution: Gender differences in the endothelin-B receptor contribution to basal cutaneous vascular tone in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE skin blood flow; laser-Doppler flowmetry; microdialysis ID BLOOD-FLOW; HUMAN SKIN; ACTIVE VASODILATION; NITRIC-OXIDE; TAIL ARTERY; HEAT-STRESS; NEUROTRANSMISSION; COTRANSMISSION; ANTAGONIST; POTENT AB To test whether the contribution of endothelin-B (ET-B) receptors to resting vascular tone differs between genders, we administered the ET-B receptor antagonist BQ-788 into the forearm skin of 11 male and 11 female subjects by intradermal microdialysis. Skin blood flow was measured using laser-Doppler flowmetry at the microdialysis site. The probe was perfused with Ringer solution alone, followed by BQ-788 (150 nM) and finally sodium nitroprusside (28 mM) to effect maximal cutaneous vasodilation. Cutaneous vascular conductance (CVC) was calculated (laser-Doppler flowmetry/mean arterial pressure) and normalized to maximal levels (% max). In male subjects, baseline CVC was (mean +/- SE) 19 +/- 3% max and increased to 26 +/- 5% max with BQ-788 (P< 0.05 vs. baseline). In female subjects, baseline CVC was 13 +/- 1% max and decreased to 10 +/- 1% max in response to BQ-788. CVC responses to BQ-788 differed with gender (P< 0.05); thus the contribution of ET-B receptors to resting cutaneous vascular tone differs between men and women. In men, ET-B receptors mediate tonic vasoconstriction, whereas, in women, ET-B receptors mediate tonic vasodilation. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. Dept Vet Affairs, Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Kellogg, DL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL-65599]; NIA NIH HHS [AG-15189] NR 28 TC 29 Z9 29 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PY 2001 VL 91 IS 5 BP 2407 EP 2411 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 486NN UT WOS:000171824000065 PM 11641388 ER PT J AU Behari, J Stagon, L Calderwood, SB AF Behari, J Stagon, L Calderwood, SB TI pepA, a gene mediating pH regulation of virulence genes in Vibrio cholerae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; LENS LEUCINE AMINOPEPTIDASE; DNA-BINDING PROTEIN; ESCHERICHIA-COLI; TRANSCRIPTIONAL ACTIVATION; COORDINATE EXPRESSION; BETA-GLUCURONIDASE; MEMBRANE PROTEINS; SUICIDE VECTOR; TOXR AB ToxT, a member of the AraC family of transcriptional regulators, controls the expression of several virulence factors in Vibrio cholerae. In the classical biotype of V. cholerae, expression of toxT is regulated by the same environmental conditions that control expression of the virulence determinants cholera toxin and the toxin coregulated pilus. Several genes that activate toxT expression have been identified. To identify genes that repress toxT expression in nonpermissive environmental conditions, a genetic screen was used to isolate mutations which alter the expression of a toxT-gusA transcriptional fusion. Several mutants were isolated, and the mutants could be divided into two classes. One class of mutants exhibited higher expression levels of toxT-gusA at both the nonpermissive pH and temperature, while the second class showed elevated toxT-gusA expression only at the nonpermissive pH. One mutant from the second class was chosen for further characterization. This mutant was found to carry a TnphoA insertion in a homolog of the Escherichia coli pepA gene. Disruption of pepA in V. cholerae resulted in elevated levels of expression of cholera toxin, tcpA, toxT, and tcpP at the noninducing pH but not at the noninducing temperature. Elevated levels of expression of toxT and tcpP at the nonpermissive pH in the pepA mutant were abolished in tcpP toxR mutant and aphB mutant backgrounds, respectively. A putative binding site for PepA was identified in the tcpPH-tcpI intergenic region, suggesting that PepA may act at the level of tcpPH transcription. Disruption of pepA caused only partial deregulation at the noninducing pH, suggesting the involvement of additional factors in the pH regulation of virulence genes in V. cholerae. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI44487] NR 57 TC 46 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2001 VL 183 IS 1 BP 178 EP 188 DI 10.1128/JB.183.1.178-188.2001 PG 11 WC Microbiology SC Microbiology GA 386UA UT WOS:000166078900021 PM 11114915 ER PT J AU Risbud, MV Hambir, S Jog, J Bhonde, R AF Risbud, MV Hambir, S Jog, J Bhonde, R TI Biocompatibility assessment of polytetrafluoroethylene/wollastonite composites using endothelial cells and macrophages SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Article DE PTFE; wollastonite; biocompatibility; endothelial cells; macrophages ID POTENTIAL ROLE; IN-VITRO; HEMODIALYSIS; PROSTHESES AB The aim of the study was to prepare a composite of polytetrafluoroethylene/wollastonite (PTFE/W) and evaluate its biocompatibility with endothelial cells. A composite of PTFE with wollastonite in the proportion 90/10 w/w was prepared. The dynamic storage modulus of composite is found to increase from 260 to about 453 MPa at room temperature while a marginal increase is observed in the compressive modulus. Higher values of storage modulus of PTFE/W relative to pristine PTFE over a range of temperature indicated the contribution of wollastonite in improving the rigidity of PTFE. Electron microscopic visualization of composite surface indicates suitable morphology for cell growth with the cross-section showing no evidence of bonding between PTFE and wollastonite. The water contact angle of the composite indicates increased hydrophilicity over native PTFE due to the presence of wollastonite. A direct-contact test did not show any deleterious effects on endothelial cell morphology and viability, indicating its compatibility. Leached-out products (LOP) from the composite were determined to be non-toxic as tested by tetrazolium (MTT) and Neutral red uptake (NRU) assays. Mouse peritoneal macrophages cultured in the presence of the composites did not show upregulation of activation markers such as CD11b/CD18 (Mac-1), CD45, CD14, and CD86 (B7.2) in comparison to macrophages cultured in contact with PTFE alone, indicating its non-activating nature. LOP did not induce proliferation of mouse splenic lymphocytes suggesting its immuno-tolerance. In static incubation assay contact with composite did not lead to hemolysis thus exhibiting preliminary hemocompatibility of the material. Suitable physico-chemical properties and well tolerance by endothelial cells and macrophages make this composite a prospective biomaterial. One could foresee the applications of this composite in areas where materials need to possess high rigidity and are subject to elevated temperatures. C1 Natl Ctr Cell Sci, Tissue Engn & Banking Lab, Pune 411007, Maharashtra, India. Natl Chem Lab, Div Chem Engn, Polymer Sci & Engn Grp, Pune 411008, Maharashtra, India. RP Risbud, MV (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. NR 28 TC 3 Z9 6 U1 0 U2 1 PU VSP BV PI ZEIST PA PO BOX 346, 3700 AH ZEIST, NETHERLANDS SN 0920-5063 J9 J BIOMAT SCI-POLYM E JI J. Biomater. Sci.-Polym. Ed. PY 2001 VL 12 IS 11 BP 1177 EP 1189 DI 10.1163/156856201753395734 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA 520XP UT WOS:000173809300002 PM 11853385 ER PT J AU Risbud, MV Bhonde, RR AF Risbud, MV Bhonde, RR TI Islet immunoisolation: experience with biopolymers SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Article ID POLYVINYL PYRROLIDONE HYDROGELS; GLUTAMIC-ACID DECARBOXYLASE; DEPENDENT DIABETES-MELLITUS; IN-VITRO BIOCOMPATIBILITY; NECROSIS-FACTOR-ALPHA; PANCREATIC-ISLETS; ALGINATE MICROCAPSULES; BIOARTIFICIAL PANCREAS; ENDOCRINE PANCREAS; NITRIC-OXIDE AB Incidence of Type I diabetes is increasing globally and has become a major health concern. There is enough evidence suggesting involvement of autoimmunity in destruction of insulin-producing islets of langerhans which leads to impaired glucose homeostasis. Islet transplantation is one of the approaches that received wide attention. Due to the autoimmune nature of the disease, strategies to protect transplanted islet graft from rejection are sought. Immunoisolation of islets inside semipermeable biocompatible materials is amongst them. Natural biopolymers have been used extensively as immunoisolation materials due to their satisfactory biocompatiblity and tissue tolerance. Here we attempt to address the need for islet immunoisolation and our experience in using natural biopolymers such as chitosan, cellulose and alginate for this application. C1 Natl Ctr Cell Sci, Tissue Engn & Banking Lab, Pune 411007, Maharashtra, India. RP Risbud, MV (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. RI BHONDE, RAMESH/C-1233-2009 NR 59 TC 9 Z9 10 U1 0 U2 0 PU VSP BV PI ZEIST PA PO BOX 346, 3700 AH ZEIST, NETHERLANDS SN 0920-5063 J9 J BIOMAT SCI-POLYM E JI J. Biomater. Sci.-Polym. Ed. PY 2001 VL 12 IS 11 BP 1243 EP 1252 DI 10.1163/156856201753395770 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA 520XP UT WOS:000173809300006 PM 11853389 ER PT J AU Klein, RF Shea, M Gunness, ME Pelz, GB Belknap, JK Orwoll, ES AF Klein, RF Shea, M Gunness, ME Pelz, GB Belknap, JK Orwoll, ES TI Phenotypic characterization of mice bred for high and low peak bone mass SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE genetics; bone mineral density; histomorphometry; biomechanics; mouse; osteoporosis ID QUANTITATIVE TRAIT LOCI; MINERAL DENSITY; RACIAL-DIFFERENCES; WHITE-CHILDREN; HIP FRACTURE; OLDER WOMEN; ILIAC BONE; AGE; BLACK; OSTEOPOROSIS AB In humans, peak bone mineral density (BMD) is a highly heritable trait and a strong determinant of subsequent osteoporotic fracture risk. To identify the genetic factors responsible for variation in peak BMD, investigators have turned to animal models. In this study we examined the heritability of BMD acquisition and characterized differences in skeletal geometry, histomorphometry, and biomechanical competence between two lines of mice artificially selected for extremes of peak whole body BMD, F-2 progeny from a cross between C57BL/6 and DBA/2 inbred strains was used as the foundation population to develop lines selected for either high or low BMD, Whole body BMD was measured by dual-energy X-ray absorptiometry (DXA), By the third generation of selection, highest-scoring BMD (HiBMD) mice exhibited 14% greater peak BMD than lowest-scoring BMD (LoBMD) mice. The mean realized heritability of peak BMD was 36%, Femoral shaft cortical area and thickness and vertebral cancellous bone volume (BV) were significantly greater (16-30%) in the HiBMD line compared with the LoBMD line, Mean cancellous bone formation rates (BFRs) were 35% lower in HiBMD mice compared with LoBMD mice. Failure load and stiffness in the femoral shaft, femoral neck, and L6 vertebrae were all substantially greater (by 25-190%) in HiBMD mice, Thus, these divergently selected murine lines serve to illustrate some of the means by which genetic mechanisms can affect skeletal structure and remodeling. Identification of the individual genes influencing peak BMD in this experimental system will likely reveal some of the genetic determinants of overall bone strength. C1 Oregon Hlth Sci Univ, Dept Med, Bone & Mineral Unit CR113, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Dept Orthopaed, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Klein, RF (reprint author), Oregon Hlth Sci Univ, Dept Med, Bone & Mineral Unit CR113, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Orwoll, Eric/0000-0002-8520-7355 FU NIAAA NIH HHS [AA 10760, P60 AA010760]; NIAMS NIH HHS [AR 44659, R01 AR044659, R01 AR044659-08] NR 36 TC 28 Z9 28 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2001 VL 16 IS 1 BP 63 EP 71 DI 10.1359/jbmr.2001.16.1.63 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 384PZ UT WOS:000165955200009 PM 11149491 ER PT J AU Chan, SK Jaffer, FA Botnar, RM Kissinger, KV Goepfert, L Chuang, ML O'Donnell, CJ Levy, D Manning, WJ AF Chan, SK Jaffer, FA Botnar, RM Kissinger, KV Goepfert, L Chuang, ML O'Donnell, CJ Levy, D Manning, WJ TI Scan reproducibility of magnetic resonance imaging assessment of aortic atherosclerosis burden SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE aorta; atherosclerosis; magnetic resonance imaging; subclinical disease ID CORONARY-ARTERY DISEASE; IN-VIVO; MYOCARDIAL-INFARCTION; PLAQUE; COMPONENTS AB Subclinical atherosclerosis precedes the onset of clinical disease by many years. Noninvasive magnetic resonance imaging (MRI) offers the opportunity to visualize and quantify atherosclerotic plaque. However, the reproducibility of MRI measurements of abdominal and thoracic aortic atherosclerosis has not been reported. Electrocardiogram-gated, T2-weighted, turbo spin echo MRI of the descending thoracic and abdominal aorta was performed on 16 subjects, comprising 10 subjects with multivessel coronary artery disease (CAD) and 6 subjects without angiographic CAD. Three identical MRIs were performed on each subject, with subject repositioning between the second and third scans. Aortic anatomic and plaque measurements were performed in a blinded fashion. Fourteen subjects (88%) had MRI evidence of atherosclerotic plaque on at least one image. Slice plaque burden, plaque area, and plaque perimeter were greater in the CAD group (52% vs. 9%, p = 0.002: 264 vs. 18 mm(2), p = 0.009; 159 vs. 15 mm, p = 0.006, respectively). Measurements of total aortic lumen area, lumen circumference, plaque area, and plaque perimeter correlated highly among the three scans (all r = 0.96, all p < 0.001). Measurements of slice-specific is aortic lumen area and lumen circumference also correlated highly (all r = 0.98, all p < 0.001). Correlations of slice-specific plaque area and plaque perimeter were significant (all p < 0.001) but less robust (r = 0.62-0.85). These data demonstrate that MRI is a reproducible technique for assessing aortic anatomy and total aortic atherosclerosis, but increased slice density should be considered if serial evaluation of slice-specific data is desired. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Harvard Thorndike Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Harvard Thorndike Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Philips Med Syst RMB, Best, Netherlands. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Manning, WJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Harvard Thorndike Lab, Boston, MA 02215 USA. RI Botnar, Rene/E-6875-2012; OI Botnar, Rene/0000-0003-2811-2509; Jaffer, Farouc/0000-0001-7980-384X NR 18 TC 37 Z9 37 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2001 VL 3 IS 4 BP 331 EP 338 DI 10.1081/JCMR-100108587 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 505KE UT WOS:000172911300007 PM 11777225 ER PT J AU Schuyler, SC Pellman, D AF Schuyler, SC Pellman, D TI Search, capture and signal: games microtubules and centrosomes play SO JOURNAL OF CELL SCIENCE LA English DT Review DE mitosis; spindle orientation; centrosome; spindle pole body; microtubule; kinesin; dynein; actin; myosin; polarity; cell cycle checkpoint ID YEAST SACCHAROMYCES-CEREVISIAE; SPINDLE POLE BODIES; CYTOPLASMIC DYNEIN; MITOTIC SPINDLE; NUCLEAR MIGRATION; CELL-CYCLE; BUDDING YEAST; FISSION YEAST; CAENORHABDITIS-ELEGANS; DYNACTIN COMPLEX AB Accurate distribution of the chromosomes in dividing cells requires coupling of cellular polarity cues with both the orientation of the mitotic spindle and cell cycle progression. Work in budding yeast has demonstrated that cytoplasmic dynein and the kinesin Kip3p define redundant pathways that ensure proper spindle orientation. Furthermore, it has been shown that the Kip3p pathway components Kar9p and Bim1p (Yeb1p) form a complex that provides a molecular link between cortical polarity cues and spindle microtubules. Recently, other studies indicated that the cortical localization of Kar9p depends upon actin cables and Myo2p, a type V myosin, In addition, a BUB2-dependent cell cycle checkpoint has been described that inhibits the mitotic exit network and cytokinesis until proper centrosome position is achieved. Combined, these studies provide molecular insight into how cells link cellular polarity, spindle position and cell cycle progression. C1 Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. RP Schuyler, SC (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [R01 GM61345-01] NR 128 TC 95 Z9 98 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN PY 2001 VL 114 IS 2 BP 247 EP 255 PG 9 WC Cell Biology SC Cell Biology GA 400NG UT WOS:000166877600002 PM 11148127 ER PT J AU Seipel, K O'Brien, SP Iannotti, E Medley, QG Streuli, M AF Seipel, K O'Brien, SP Iannotti, E Medley, QG Streuli, M TI Tara, a novel F-actin binding protein, associates with the Trio guanine nucleotide exchange factor and regulates actin cytoskeletal organization SO JOURNAL OF CELL SCIENCE LA English DT Article DE Rho; Rac; Db1 homology; Trio; actin-binding protein; pleckstrin homology; coiled-coil ID PLECKSTRIN-HOMOLOGY DOMAIN; KINASE RHO-KINASE; TYROSINE-PHOSPHATASE; P21-ACTIVATED KINASE; FOCAL ADHESIONS; CELL-MIGRATION; STRESS FIBERS; COILED COILS; IN-VIVO; MYOSIN AB Reorganization of the actin cytoskeleton is essential to numerous cellular processes including cell locomotion and cytokinesis, This actin remodeling is regulated in part by Rho family GTPases, Previous studies implicated Trio, a Dbl-homology guanine nucleotide exchange factor with two exchange factor domains, in regulating actin cytoskeleton reorganization, cell motility and cell growth via activation of Rho GTPases, Trio is essential for mouse embryonic development and Trio-deficiency is associated with abnormal skeletal muscle and neural tissue development, Furthermore, genetic analyses in Caenorhabditis elegans and Drosophila demonstrate a role for trio-like genes in cell migration and axon guidance, Herein we characterize a novel Trio-binding protein, Tara, that is comprised of an N-terminal pleckstrin homology domain and a C-terminal coiled-coil region, Trio and Tara associate as assessed by the yeast interaction-trap assays and mammalian coimmunoprecipitation studies, Ectopically expressed Tara localizes to F-actin in a periodic pattern that is highly similar to the pattern of myosin II, Furthermore, a direct interaction between Tara and F-actin is indicated by in vitro binding studies. Cells that transiently or stably overexpress Tara display an extensively flattened cell morphology with enhanced stress fibers and cortical F-actin, Tara expression does not alter the ability of the cell to attach or to initially spread, but rather increases cell spreading following these initial events. Tara stabilizes F-actin structures as indicated by the relative resistance of Tara-expressing cells to the F-actin destabilizer Latrunculin B, We propose that Tara regulates actin cytoskeletal organization by directly binding and stabilizing F-actin, and that the localized formation of Tara and Trio complexes functions to coordinate actin remodeling. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Streuli, M (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA55547, CA75091] NR 52 TC 43 Z9 49 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN PY 2001 VL 114 IS 2 BP 389 EP 399 PG 11 WC Cell Biology SC Cell Biology GA 400NG UT WOS:000166877600015 PM 11148140 ER PT J AU Joung, JK AF Joung, JK TI Identifying and modifying protein-DNA and protein-protein interactions using a bacterial two-hybrid selection system SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 5th Annual Lake Tahoe Symposium CY JAN 29-FEB 02, 2001 CL LOS ANGELES, CALIFORNIA DE two-hybrid selections; protein-DNA; protein-protein; interaction trap ID ACTIVATION; TARGET AB A bacterial two-hybrid system based on transcriptional activation in E. coli has recently been described. A variety of different protein-DNA and protein-protein interactions from bacteria, yeast, and humans have been studied using this bacterial-based system. The method, because it is based in bacteria, offers significant advantages relative to its yeast counterpart including the ability to analyze complex libraries >10(8) in size, ease of use, and speed. The ability to easily and rapidly process very large libraries make this system a powerful tool for identifying, modifying, or optimizing protein-DNA and protein-protein interactions. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Div Mol Pathol & Res, Dept Pathol, Charlestown, MA 02129 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Div Mol Pathol & Res, Dept Pathol, 149 13th St,7th Floor, Charlestown, MA 02129 USA. EM jjoung@partners.org NR 12 TC 1 Z9 1 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 84 SU 37 BP 53 EP 57 DI 10.1002/jcb.10065 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 520VN UT WOS:000173803200009 ER PT J AU Baltathakis, L Alcantara, O Boldt, DH AF Baltathakis, L Alcantara, O Boldt, DH TI Expression of different NF-kappa B pathway genes in dendritic cells (DCs) or macrophages assessed by gene expression profiling SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE NF-kappa B; dendritic cells; macrophages; cDNA arrays ID TOLL-LIKE RECEPTOR-2; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SERIAL ANALYSIS; LIPOPOLYSACCHARIDE; TRANSCRIPTION; RELB; MATURATION; FAMILY AB NF-kappaB/Rel transcription factors have been implicated in the differentiation of monocytes to either dendritic cells (DCs) or macrophages, as well as in the maturation of DCs from antigen-processing to antigen-presenting cells. Recent studies of the expression pattern of Rel proteins and their inhibitors (I kappa BS) suggest that their regulation during this differentiation process is transcriptional. To investigate differential gene expression between macrophages and DCs, we used commercially available gene microarrays (GEArray KIT), which included four of the NF-kappaB/Rel family genes (p50/p1 05, p52/p100, ReIB, and c-rel) and 32 additional genes either in the NF-kappaB signal transduction pathway or under transcriptional control of NF-kappaB/Rel factors. To generate macrophages and DCs, human adherent peripheral blood monocytes were cultured with M-CSF or GM-CSF+IL-4 respectively for up to 8 days. DCs (and in some experiments, macrophages) were treated with lipopolysaccharide (LPS) for the last 48 h of culture to induce maturation. Cells were harvested after 7 days, cDNA was prepared and radiolabeled with alpha-P-32-dCTP, then hybridized to gene arrays containing specific gene probes. P-actin and GAPDH or PUC18 oligonucleotides served as positive or negative controls, respectively. The expression of all four NF-kappaB/Rel family genes examined was significantly upregulated in maturing DCs compared to macrophages. The strongest difference was observed for c-rel. RT-PCR determinations of c-rel, RelB, and p105 mRNAs confirmed these observations. Among the 32 NF-kappaB/Rel pathway genes, 14 were upregulated in mature DCs compared to macrophages. These genes were I kappaB alpha, IKK-beta, NIK, ICAM-1, P-selectin, E-selectin, TNF-alpha, TNFR2, TNFAIP3, IL-1 alpha, IL-1R1, IL-1R2, IRAK, and TANK. By contrast, only mcp-1 (monocyte chemotactic protein 1) was upregulated in macrophages compared to DCs. NF-KB pathway genes upregulated in DCs compared to macrophages were constitutively expressed in monocytes then selectively downregulated during macrophage but not DC differentiation. LPS did not induce expression of most of these genes in macrophages but LPS did induce upregulation of IL-8 in mature macrophages. We conclude that NF-kappaB/Rel family genes, especially c-rel, are selectively expressed during differentiation of monocytes towards DCs. Moreover, this differential expression is associated both with activation of different NF-kappaB signal transduction pathways in DCs and macrophages and with expression of a unique subset of genes in DCs that are transcriptionally targeted by NF-kappaB/Rel factors. The results illustrate the ability of the NF-kappaB pathway to respond to differentiation stimuli by activating in a cell-specific manner unique signalling pathways and subsets of NF-kappaB target genes. (C) 2001 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Boldt, DH (reprint author), Univ Texas, Hlth Sci Ctr, Mail Code 7880,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 32 TC 17 Z9 17 U1 4 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 83 IS 2 BP 281 EP 290 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 475BJ UT WOS:000171141500011 ER PT J AU Wu, EX Mari, BP Wang, FF Anderson, IC Sunday, ME Shipp, MA AF Wu, EX Mari, BP Wang, FF Anderson, IC Sunday, ME Shipp, MA TI Stromelysin-3 suppresses tumor cell apoptosis in a murine model SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE matrix metalloproteinase; tumor incidence; processing; stroma ID BREAST-CANCER; MESSENGER-RNA; IN-VIVO; EXPRESSION; CARCINOMA; MATRIX; GENE; PROGRESSION; ACTIVATION; GROWTH AB Stromelysin-3 (STR-3) is a matrix metalloproteinase with a unique pattern of expression and substrate specificity. During embryogenesis and remodeling of normal adult tissues, STR-3 is produced by stromal cells in direct contact with epithelial cells undergoing regional apoptosis and selective cell survival. STR-3 is also overexpressed by interdigitating stromal cells in primary epithelial malignancies. Although STR-3 does not degrade classic extracellular matrix components, the enzyme promotes the establishment of local tumors in nude mice by as yet undefined mechanisms. STR-3 is induced when malignant epithelial cells come into contact with surrounding stromal elements; the active stromal cell-derived 45 kDa enzyme is subsequently processed to a 35 kDa protein without enzymatic activity. We have generated MCF-7 transfectants expressing wild type or catalytically inactive 45 kDa STR-3 (STR-3(wt) and STR-3(cat).) or secreted 35 kDa STR-3 (35 kDa STR-3(sec)) and evaluated their implantation and survival in nude mice. Tumors developed significantly more rapidly in animals receiving STR-3(wt), rather than vector-only, STR-3(cat). or 35 kDa STR-3(sec) transfectants. Most importantly, STR-3(wt) tumors had a significantly lower percentage of apoptotic cells than tumors derived from vector-only, STR-3(cat-) or 35 kDa STR-3(sec) transfectants. Taken together, these studies suggest that the active STR-3 enzyme may increase tumor take by suppressing tumor cell apoptosis and that 45 kDa to 35 kDa STR-3 processing limits STR-3 activity at the tumor/stromal interface. Because STR-3 is secreted as an active enzyme rather than a proform, subsequent 45 kDa to 35 kDa STR-3 processing may represent a novel mechanism for regulating enzymatic activity. (C) 2001 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Mari, Bernard/F-8960-2013; Mari, Bernard/D-7445-2015 OI Mari, Bernard/0000-0002-0422-9182 NR 28 TC 38 Z9 45 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 82 IS 4 BP 549 EP 555 DI 10.1002/jcb.1181 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 459BE UT WOS:000170229300002 PM 11500932 ER PT J AU Mueller, SM Glowacki, J AF Mueller, SM Glowacki, J TI Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE bone marrow; aging; osteogenesis; in vitro; three-dimensional ID OSTEOBLAST PRECURSOR CELLS; HUMAN DERMAL FIBROBLASTS; MESENCHYMAL STEM-CELLS; STROMAL CELLS; IN-VITRO; OSTEOPROGENITOR CELLS; 3-DIMENSIONAL CULTURE; DEMINERALIZED BONE; ESTROGEN STATUS; DIFFERENTIATION AB Studies with human and animal culture systems indicate that a sub-population of bone marrow stromal cells has the potential to differentiate into osteoblasts. There are conflicting reports on the effects of age on human marrow-derived osteogenic cells. In this study, we used a three dimensional (3D) culture system and quantitative RT-PCR methods to test the hypothesis that the osteogenic potential of human bone marrow stromal cells decreases with age. Marrow was obtained from 39 men aged 37 to 86 years, during the course of total hip arthroplasty. Low-density mononuclear cells were seeded onto 3D collagen sponges and cultured for 3 weeks. Histological sections of sponges were stained for alkaline phosphatase activity and were scored as positive or negative. In the group less than or equal to 50 years, 7 of 11 samples (63%) were positive, whereas only 5 of 19 (26%) of the samples in the group greater than or equal to 60 years were positive (p=0.0504). As revealed by RT-PCR, there was no expression of alkaline phosphatase or collagen type I mRNA before culture, however there were strong signals after 3 weeks, an indication of osteoblast differentiation in vitro. We performed a quantitative, competitive RT-PCR assay with 8 samples (age range 38-80) and showed that the group less than or equal to 50 years had 3-fold more mRNA for alkaline phosphatase than the group greater than or equal to 60 years (p=0.021). There was a significant decrease with age (r=-0.78, p=0.028). These molecular and histoenzymatic data indicate that the osteogenic potential of human bone marrow cells decreases with age. (C) 2001 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Glowacki, J (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. FU NIA NIH HHS [AG12271, AG13519] NR 50 TC 247 Z9 289 U1 1 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 82 IS 4 BP 583 EP 590 DI 10.1002/jcb.1174 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 459BE UT WOS:000170229300006 PM 11500936 ER PT J AU Stock, UA Wiederschain, D Kilroy, SM Shum-Tim, D Khalil, PN Vacanti, JP Mayer, JE Moses, MA AF Stock, UA Wiederschain, D Kilroy, SM Shum-Tim, D Khalil, PN Vacanti, JP Mayer, JE Moses, MA TI Dynamics of extracellular matrix production and turnover in tissue engineered cardiovascular structures SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE extracellular matrix; remodeling; tissue engineering; blood vessels ID SMOOTH-MUSCLE CELLS; ENDOGENOUS INHIBITORS; ENDOTHELIAL-CELLS; PRIMARY CULTURE; METALLOPROTEINASES; EXPRESSION; RAT; IDENTIFICATION; COLLAGENASE; RABBIT AB Appropriate matrix formation, turnover and remodeling in tissue-engineered small diameter vascular conduits are crucial requirements for their long-term patency and function. This complex process requires the deposition and accumulation of extracellular matrix molecules as well as the remodeling of this extracellular matrix (ECM) by matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs). In this study, we have investigated the dynamics of ECM production and the activity of MMPs and TIMPs in long-term tissue-engineered vascular conduits using quantitative ECM analysis, substrate gel electrophoresis, radiometric enzyme assays and Western blot analyses. Over a time period of 169 days in vivo, levels of elastin and proteoglycans/glycosaminoglycans in tissue-engineered constructs came to approximate those of their native tissue counter parts. The kinetics of collagen deposition and remodeling, however, apparently require a much longer time period. Through the use of substrate gel electrophoresis, proteolytic bands whose molecular weight was consistent with their identification as the active form of MMP-2 (approximate to 64-66 kDa) were detected in ail native and tissue-engineered samples. Additional proteolytic bands migrating at approximate to 72 kDa representing the latent form of MMP-2 were detected in tissue-engineered samples at time points from 5 throughout 55 days. Radiometric assays of MMP-1 activity demonstrated no significant differences between the native and tissue-engineered samples. This study determines the dynamics of ECM production and turnover in a long-term tissue-engineered vascular tissue and highlights the importance of ECM remodeling in the development of successful tissue-engineered vascular structures. (C) 2001 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Cardiovasc Surg, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Tissue Engn Lab, Boston, MA 02114 USA. RP Stock, UA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Tissue Engn Lab, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-97-005] NR 35 TC 40 Z9 41 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 81 IS 2 BP 220 EP 228 DI 10.1002/1097-4644(20010501)81:2<220::AID-JCB1037>3.0.CO;2-O PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 419BM UT WOS:000167929500002 PM 11241662 ER PT J AU Fang, MA Glackin, CA Sadhu, A McDougall, S AF Fang, MA Glackin, CA Sadhu, A McDougall, S TI Transcriptional regulation of alpha 2(1) collagen gene expression by fibroblast growth factor-2 in MC3T3-E1 osteoblast-like cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE FGF-2; transcription factor; helix-loop-helix; Egr-1; osteoblast ID SAETHRE-CHOTZEN-SYNDROME; EGR-1 MESSENGER-RNA; EARLY-RESPONSE GENES; C-FOS; TWIST; PROTEIN; ACID; DIFFERENTIATION; ENHANCEMENT; ACTIVATION AB Fibroblast growth factor-2 (FGF-2) stimulates proliferation and inhibits differentiated function of osteoblasts by suppressing synthesis of type I collagen and other proteins. However, little is known regarding the molecular mechanisms regulating the suppressive effects of FGF-2 on type I collagen synthesis in osteoblasts. The zinc finger transcription factor Egr-1: and the basic helix-loop-helix (bHLH) family of proteins have been implicated in the regulation of genes crucial to mesodermal cell growth and differentiation. The aim of this study was to determine whether Egr-1 and TWIST might be potential transcriptional regulators of the inhibitory effects of FGF-2 on alpha2(I) collagen expression in MC3T3-E1 osteoblasts which undergo a developmental sequence in vitro. Upon treatment of undifferentiated MC3T3-E1 cells with 1 nM FGF-2, Egr-1 mRNA increased with the effect maximal after 30-60 min. TWIST mRNA also increased with the effect maximal at 2 h. We analyzed the transcriptional control of alpha2(I) collagen gene expression by FGF-2 by transient transfection of an alpha2(I) collagen-luciferase construct (pH5) into undifferentiated MC3T3-E1 cells. The activity of the pH5 luciferase promoter decreased in a dose-dependent manner following treatment with.01 and 1 nM FGF-2. We identified putative Egr-1: and TWIST recognition sequences in the proximal region of the promoter for the murine alpha2(I) collagen gene and a putative Egr-1 site in the 5' region of the murine TWIST promoter. In gel mobility shift assays, potential Egr-1 response elements in the 5' region of the murine TWIST and alpha2(I) collagen genes demonstrated specific Egr-1 binding activity with bFGF-treated nuclear extracts obtained from MC3T3-E1 cells. These results indicate that Egr-1 and TWIST are expressed in undifferentiated MC3T3-E1 osteoblast-like cells following treatment with FGF-2 and they may be potential transcriptional regulators of FGF-2s negative effects on alpha2(I) collagen gene expression. J. Cell. Biochem. 80:550-559, 2001. Published 2001 Wiley-Liss, Inc.dagger C1 VA Greater Los Angeles Healthcare Syst, GRECC 11G, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. City Hope Natl Med Ctr, Div Mol Med, Duarte, CA 91010 USA. RP Fang, MA (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC 11G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIA NIH HHS [K12 AG-00489] NR 42 TC 29 Z9 30 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 80 IS 4 BP 550 EP 559 DI 10.1002/1097-4644(20010315)80:4<550::AID-JCB1009>3.3.CO;2-T PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 398KA UT WOS:000166754600010 PM 11169739 ER PT J AU Daniels, GH AF Daniels, GH TI Clinical review 120 - Amiodarone-induced thyrotoxicosis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID IODIDE-INDUCED THYROTOXICOSIS; THYROID-HORMONE ACTION; INDUCED HYPERTHYROIDISM; AUTOIMMUNE-THYROIDITIS; IN-VITRO; THERAPY; HYPOTHYROIDISM; DYSFUNCTION; DISEASE C1 Massachusetts Gen Hosp, Thyroid Unit ACC 730, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Thyroid Unit ACC 730, Boston, MA 02114 USA. EM Gdaniels@Partners.org NR 54 TC 73 Z9 76 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2001 VL 86 IS 1 BP 3 EP 8 DI 10.1210/jc.86.1.3 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 395KT UT WOS:000166580100001 PM 11231968 ER PT J AU Leach, RJ Singer, FR Roodman, GD AF Leach, RJ Singer, FR Roodman, GD TI Genetics of endocrine disease - The genetics of Paget's disease of the bone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OSTEOCLASTOGENESIS-INHIBITORY FACTOR; FAMILIAL EXPANSILE OSTEOLYSIS; CHROMOSOME 18Q; LINKAGE; OSTEOPROTEGERIN; LIGAND; HLA; DIFFERENTIATION; TUMOR C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Vet Adm Hosp, Dept Med, San Antonio, TX 78284 USA. St Johns Hosp & Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA 90404 USA. RP Roodman, GD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Hematol 7880, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM roodman@uthscsa.edu NR 39 TC 28 Z9 30 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2001 VL 86 IS 1 BP 24 EP 28 DI 10.1210/jc.86.1.24 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 395KT UT WOS:000166580100005 PM 11231972 ER PT J AU Hayes, FJ Decruz, S Seminara, SB Boepple, PA Crowley, WF AF Hayes, FJ Decruz, S Seminara, SB Boepple, PA Crowley, WF TI Differential regulation of gonadotropin secretion by testosterone in the human male: Absence of a negative feedback effect of testosterone on follicle-stimulating hormone secretion SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the Endocrine-Society CY JUN 12-16, 1999 CL SAN DIEGO, CA SP Endocrine Soc ID MONKEY MACACA-MULATTA; DOSE KETOCONAZOLE THERAPY; CLINICAL RESEARCH-CENTER; INHIBIN-B SECRETION; SEX STEROID CONTROL; LUTEINIZING-HORMONE; DEFICIENT MEN; CIRCULATING CONCENTRATIONS; AROMATASE DEFICIENCY; PROSTATIC-CANCER AB Studies of sex steroid regulation of gonadotropin secretion in the human male have focused primarily on the respective site(s) of negative feedback of testosterone (T) and estradiol (E(2)). The use of pharmacological doses of sex steroids in these studies has precluded conclusions about the relative roles of T and E(2) in gonadotropin feedback. Thus, the aims of the present study were to 1) determine the relative contributions of T vs. E(2) to the sex steroid component of gonadotropin regulation, and 2) distinguish the feedback effects of T that that are direct (i.e. mediated by the androgen receptor) vs. indirect (mediated by aromatization to E(2)). Two experimental interventions were used: 1) inhibition of aromatization by a selective aromatase inhibitor to examine the impact of selective E(2) withdrawal; and 2) acute medical castration to examine the effect of ablating both T and E(2). Sixteen normal (NL) men (mean age, 30.5 +/- 2.2 yr) were studied. Nine NL subjects were treated with the aromatase inhibitor, anastrozole (10 mg, orally, daily, for 5 days). Twelve NL men underwent medical castration with ketoconazole (1-g loading dose followed by 400 mg, orally, four times a day for 5 days). Ketoconazole-treated subjects received concomitant treatment with dexamethasone (0.5 mg twice daily) to prevent the development of adrenal insufficiency. Single blood samples were drawn daily between 0800-1000 h. To ensure that dexamethasone was not altering the gonadotropin response to sex steroid ablation by a direct pituitary effect, live GnRH-deficient men (mean age, 37.6 +/- 3.9 yr) underwent GnRH dose-response studies at baseline and after treatment with dexamethasone (0.5 mg twice daily). Aromatase blockade caused significant lowering of E(2) (33 +/- 3 to 14 +/- 1 pg/mL; P < 0.0005) with a corresponding increase in T levels (563 +/- 42 to 817 +/- 81 ng/dL; P < 0.05). Treatment with ketoconazole resulted in equivalent suppression of E(2) (41 +/- 4 to 14 +/- 1 pg/mL; P < 0.0005), but also induced castrate levels of T (491 +/- 28 to 40 +/- 3 ng/dL; P < 0.0005). Both treatment regimens were associated with a significant increase in gonadotropin levels. For LH, the percent increase in serum levels after castration was almost 3-fold greater than that seen after selective E(2) withdrawal (275 +/- 23% with ketoconazole us. 95.6 +/- 21% with anastrozole; P < 0.005). Despite the divergent changes in T levels with these two maneuvers (a marked decrease after ketoconazole and a significant increase with anastrozole), the percent rise in FSH levels was similar in the two protocols (91 +/- 6% vs. 71 +/- 7%, respectively; P = NS). Inhibin B levels were unchanged after selective E(2) withdrawal (156 +/- 23 vs. 176 +/- 19 pg/mL), but decreased slightly with ketoconazole (156 +/- 15 to 131 +/- 11 pg/mL; P < 0.05). In contrast to the effects of glucocorticoid administration on gonadotropin secretion in women, no significant changes were observed in the GnRH-deficient men treated with dexamethasone in terms of mean LH levels (19.8 +/- 3.2 vs. 23.3 +/- 5.4 IU/L), mean LH pulse amplitude after GnRH (16.0 +/- 2.5 vs. 19.0 +/- 5.1 IU/L), or mean FSH levels (8.0 +/- 1.9 vs. 9.2 +/- 2.4 IU/L, pre vs. post). These studies provide evidence of differential regulation of gonadotropin secretion by T in the human male. T exerts both direct and indirect feedback on LH secretion, whereas its effects on FSH appear to be mediated largely by aromatization to E(2). From these data we conclude that in terms of sex steroid feedback, E(2) is the predominant regulator of FSH secretion in the human male. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Fruit St, Boston, MA 02114 USA. EM hayes.frances@mgh.harvard.edu FU NCRR NIH HHS [MO1-RR-01066]; NICHD NIH HHS [R01 HD015788, R01-HD-15788-15, U54 HD028138, U54 HD029164]; NIDDK NIH HHS [DK-07028-24] NR 67 TC 90 Z9 93 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2001 VL 86 IS 1 BP 53 EP 58 DI 10.1210/jc.86.1.53 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 395KT UT WOS:000166580100011 PM 11231978 ER PT J AU Welt, CK Schneyer, AL AF Welt, CK Schneyer, AL TI Differential regulation of inhibin B rand inhibin A by follicle-stimulating hormone and local growth factors in human granulosa cells from small antral follicles SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; POLYCYSTIC-OVARIAN-SYNDROME; HUMAN MENSTRUAL-CYCLE; DIMERIC INHIBIN; LUTEAL CELLS; ALPHA-SUBUNIT; ACTIVIN-A; IGF-I; LUTEINIZING-HORMONE; RAT INHIBIN AB Serum inhibin B rises across the luteal-follicular transition, whereas inhibin A does not increase until the late follicular phase of the menstrual cycle. To test the hypothesis that inhibin B is secreted from preantral and small antral follicles and that FSH and local growth factors differentially regulate inhibin B and inhibin A from these developing follicles, human ovaries were obtained after oophorectomy. Basal secretion of inhibin B and inhibin A was examined in intact preantral follicles in culture (n = 6). Basal secretion and regulation of inhibin B and inhibin A secretion by gonadotropins, androstenedione, activin A, insulin, and IGF-I were examined in cultured granulosa cells from small antral follicles (n = 21). Inhibin B secretion from preantral follicle cultures was detectable at baseline (range, 17-96 pg/mL), whereas inhibin A was not detectable. In contrast, both inhibin B and inhibin A were detectable in granulosa cell cultures from small antral follicles. In granulosa cells from small antral follicles, FSH (30 ng/mL) stimulated inhibin A 3-fold (10.5 +/- 2.2 to 32.5 +/- 8.3 IU/mL; P < 0.001), but not inhibin B secretion (1730 +/- 354 to 2314 +/- 532 pg/mL; P = NS). Likewise, cAMP (1 mmol/L) stimulated inhibin A 4-fold (16.6 +/- 4.3 to 62.5 +/- 21.9 IU/mL; P < 0.002), but not inhibin B secretion (2327 +/- 546 to 1877 +/- 377 pg/mL; P = NS). hCG (30 ng/mL) did not stimulate inhibin A or inhibin B. Androstenedione (10-7 mol/L), activin (30 ng/mL), insulin (30 ng/mL), and insulin-like growth factor I (IGF-I; 100 ng/mL) alone did not stimulate inhibin A or inhibin B secretion. Further, FSH-stimulated inhibin A secretion was not augmented by androstenedione, activin, insulin, or IGF-I. In contrast, the combination of IGF-I and FSH was the only treatment that stimulated inhibin B secretion (1742 +/- 380 to 2881 +/- 731 pg/mL; P < 0.03). However, FSH in combination with IGF-T resulted in greater stimulation of inhibin A (340%) than inhibin B (65%). These findings demonstrate that inhibin B is secreted from developing preantral and small antral follicles, but is not directly stimulated by FSH. However, the combination of FSH and IGF-I enhanced inhibin B secretion. In contrast, inhibin A is not secreted from preantral follicles, but in small antral follicles FSH and cAMP stimulate inhibin A secretion. Further, FSH in combination with IGF-I results in a greater degree of stimulation of inhibin A than of inhibin B. These findings suggest that FSH and IGF-I differentially regulate inhibin A and inhibin B secretion. However, additional growth factors or increasing granulosa cell number may contribute to the preferential serum inhibin B increase across the luteal-follicular transition in the menstrual cycle. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [MO1-RR-1066]; NICHD NIH HHS [U54-HD-29164, P30-HD-28138] NR 46 TC 62 Z9 62 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2001 VL 86 IS 1 BP 330 EP 336 DI 10.1210/jc.86.1.330 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 395KT UT WOS:000166580100053 PM 11232020 ER PT J AU Muller, B White, JC Nylen, ES Snider, RH Becker, KL Habener, JF AF Muller, B White, JC Nylen, ES Snider, RH Becker, KL Habener, JF TI Ubiquitous expression of the calcitonin-I gene in multiple tissues in response to sepsis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TRANS-GOLGI NETWORK; PROCALCITONIN CONCENTRATIONS; ENDOPROTEOLYTIC CLEAVAGE; SYSTEMIC INFLAMMATION; SERUM PROCALCITONIN; PERMEABILIZED CELLS; RNA; PROSOMATOSTATIN; INHIBITION; INFECTION AB Calcitonin precursors (CTpr), including procalcitonin, are important markers and also potentially harmful mediators in response to microbial infections. The source and function of CTpr production in sepsis, however, remains an enigma. In the classical view, the transcription of the CT-I gene is restricted to neuroendocrine cells, in particular the C cells of the thyroid. To better understand the pathophysiology of CTpr induction in sepsis, we used an animal model analog to human sepsis, in which bacterial infection is induced in hamsters by implanting Escherichia coli pellets ip. Compared with control hamsters, levels of CTpr mere elevated several fold in septic plasma and in nearly all septic hamster tissues analyzed. Unexpectedly, CT-messenger RNA was ubiquitously and uniformly expressed in multiple tissues throughout the body in response to sepsis. Notably, the transcriptional expression of CT-messenger RNA seemed more widely up-regulated in sepsis than were classical cytokines (e.g. tumor necrosis factor-alpha and interleukin-6). Our findings, which describe a potentially new mechanism of host response to a microbial infection mediated by CTpr, introduce a new pathophysiological role for the CT-I gene. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. George Washington Univ, Dept Surg & Med, Washington, DC 20422 USA. RP Muller, B (reprint author), Univ Basel Hosp, Dept Internal Med, Div Endocrinol Diabetol & Clin Nutr, Petersgraben 4, CH-4031 Basel, Switzerland. EM happymiller@bigfoot.com NR 29 TC 224 Z9 243 U1 1 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2001 VL 86 IS 1 BP 396 EP 404 DI 10.1210/jc.86.1.396 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 395KT UT WOS:000166580100064 PM 11232031 ER PT J AU Pisegna, JR AF Pisegna, JR TI Switching between intravenous and oral pantoprazole SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE proton pump; pantoprazole; gastroesophageal reflux; Zollinger-Ellison syndrome; peptic ulcer; stress ulcer; syndrome; acid aspiration ID GASTROESOPHAGEAL REFLUX DISEASE; PROTON-PUMP INHIBITORS; ZOLLINGER-ELLISON SYNDROME; STRESS-ULCER PROPHYLAXIS; GASTRIC-ACID SECRETION; NONCARDIAC CHEST PAIN; PEPTIC-ULCER; INTRAGASTRIC PH; DOUBLE-BLIND; OMEPRAZOLE SUSPENSION AB Proton pump inhibitors (PPIs) are the most effective antisecretory drugs available for controlling gastric acid acidity and volume. They are the drugs of choice in the treatment of moderate-to-severe gastroesophageal reflux disease, hypersecretory disorders, and peptic ulcers. Currently in the United States, they are only available in an oral formulation. However, pantoprazole will soon be available in an intravenous formulation and will extend the power of PPIs to inpatient hospital settings. Intravenous pantoprazole has been shown to be effective and safe in clinical trials. Intravenous pantoprazole is indicated for the treatment of patients who require PPI therapy but who are unable to take oral medication. Intravenous pantoprazole has been shown to maintain acid suppression in patients switched from oral PPIs, so no change in dosage is required when switching from one formulation to the other. Potential hospital-based uses for intravenous PPI therapy include perioperative use as prophylaxis for acid aspiration syndrome during induction of anesthesia, prophylaxis for stress-related mucosal disease, and management of gastrointestinal bleeding from stress or acid peptic disease. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. RP Pisegna, JR (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Bldg 115,Room 315,1301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 62 TC 17 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JAN PY 2001 VL 32 IS 1 BP 27 EP 32 DI 10.1097/00004836-200101000-00007 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 385XX UT WOS:000166031400007 PM 11154164 ER PT J AU Krane, SM AF Krane, SM TI Petulant cellular acts: destroying the ECM rather than creating it SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID MATRIX METALLOPROTEINASES; I COLLAGEN; RECEPTOR; CELLS C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Arthrit Unit, Boston, MA 02114 USA. RP Krane, SM (reprint author), Harvard Univ, Sch Med, Dept Med, 55 Fruit St, Boston, MA 02114 USA. NR 23 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2001 VL 107 IS 1 BP 31 EP 32 DI 10.1172/JCI11892 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 389GY UT WOS:000166231300007 PM 11134176 ER PT J AU Sonntag, KC Emery, DW Yasumoto, A Haller, G Germana, S Sablinski, T Shimizu, A Yamada, K Shimada, H Arn, S Sachs, DH LeGuern, C AF Sonntag, KC Emery, DW Yasumoto, A Haller, G Germana, S Sablinski, T Shimizu, A Yamada, K Shimada, H Arn, S Sachs, DH LeGuern, C TI Tolerance to solid organ transplants through transfer of MHC class II genes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RETROVIRUS-MEDIATED TRANSFER; T-CELLS; BONE-MARROW; MONOCLONAL-ANTIBODIES; RENAL-ALLOGRAFTS; IN-VIVO; MINIATURE SWINE; HLA-DR; EXPRESSION; REJECTION AB Donor/recipient MHC class II. matching permits survival of experimental allografts without permanent immunosuppression, but is not clinically applicable due to the extensive polymorphism of this locus. As an alternative, we have tested a gene therapy approach in a preclinical animal model to determine whether expression of allogeneic class II transgenes (Tg's) in recipient bone marrow cells would allow survival of subsequent Tg-matched renal allografts. Somatic matching between donor kidney class II and the recipient Tg's, in combination with a short treatment of cyclosporine A, prolonged graft survival with DR and promoted tolerance with DQ. Class II Tg expression in the lymphoid lineage and the graft itself were sequentially implicated in this tolerance induction. These results demonstrate the potential of MHC class II gene transfer to permit tolerance to solid organ allografts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Univ Washington, Div Med Genet, Seattle, WA 98195 USA. Chiba Univ, Sch Med, Dept Surg 2, Chiba, Japan. Klinikum Mannheim GmbH, Chirurg Klin, Mannheim, Germany. Novartis Pharmaceut, Clin Res & Dev, E Hanover, NJ USA. Nippon Med Sch, Dept Pathol, Tokyo, Japan. RP LeGuern, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [5RO1 HL46532]; NIAID NIH HHS [2RO1 AI31046, R01 AI031046] NR 35 TC 60 Z9 62 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2001 VL 107 IS 1 BP 65 EP 71 DI 10.1172/JCI11015 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 389GY UT WOS:000166231300012 PM 11134181 ER PT J AU Rui, LY Aguirre, V Kim, JK Shulman, GI Lee, A Corbould, A Dunaif, A White, MF AF Rui, LY Aguirre, V Kim, JK Shulman, GI Lee, A Corbould, A Dunaif, A White, MF TI Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser(307) via distinct pathways SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; 3T3-L1 ADIPOCYTES; SERINE/THREONINE PHOSPHORYLATION; KINASE-ACTIVITY; PROTEIN-KINASE; RESISTANCE AB Serine/threonine phosphorylation of IRS-1 might inhibit insulin signaling, but the relevant phosphorylation sites are difficult to identify in cultured cells and to validate in isolated tissues. Recently, we discovered that recombinant NH2-terminal Jun kinase phosphorylates IRS-1 at Ser(307), which inhibits insulin-stimulated tyrosine phosphorylation of IRS-1. To monitor phosphorylation of Ser(307) in various cell and tissue backgrounds, we prepared a phosphospecific polyclonal antibody designated alpha pSer(307). This antibody revealed that TNF-alpha, IGF-1, or insulin stimulated phosphorylation of IRS-1 at Ser(307) in 3T3-L1 preadipocytes and adipocytes. Insulin injected into mice or rats also stimulated phosphorylation of Ser(307) on IRS-1 immunoprecipitated from muscle; moreover, Ser(307) was phosphorylated in human muscle during the hyperinsulinemic euglycemic clamp. Experiments in 3T3-L1 preadipocytes and adipocytes revealed that insulin-stimulated phosphorylation of Ser(307) was inhibited by LY294002 or wortmannin, whereas TNF-alpha -stimulated phosphorylation was inhibited by PD98059. Thus, distinct kinase pathways might converge at Ser(307) to mediate feedback or heterologous inhibition of IRS-1 signaling to counterregulate the insulin response. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Yale Univ, Sch Med, Dept Internal Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Rui, LY (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. FU NCRR NIH HHS [RR 02635]; NIDDK NIH HHS [R01 DK 40605, R01 DK040936] NR 36 TC 354 Z9 379 U1 1 U2 16 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2001 VL 107 IS 2 BP 181 EP 189 DI 10.1172/JCI10934 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 393FE UT WOS:000166457900009 PM 11160134 ER PT J AU Echtermeyer, F Streit, M Wilcox-Adelman, S Saoncella, S Denhez, F Detmar, M Goetinck, PF AF Echtermeyer, F Streit, M Wilcox-Adelman, S Saoncella, S Denhez, F Detmar, M Goetinck, PF TI Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIN STRESS FIBERS; FOCAL ADHESIONS; SIGNAL-TRANSDUCTION; GENE; EXPRESSION; INTEGRINS; CYTOSKELETON; PROTEIN AB The syndecans make up a family of transmembrane heparan sulfate proteoglycans that act as coreceptors with integrins and growth factor tyrosine kinase receptors. Syndecan-4 is upregulated in skin dermis after wounding, and, in cultured fibroblasts adherent to the ECM protein fibronectin, this proteoglycan signals cooperatively with beta (1) integrins. In this study, we generated mice in which the syndecan-4 gene was disrupted by homologous recombination in embryonic stem cells to test the hypothesis that syndecan-4 contributes to wound repair. Mice heterozygous or homozygous for the disrupted syndecan-4 gene are viable, fertile, and macroscopically indistinguishable from wild-type littermates. Compared with wild-type littermates, mice heterozygous or homozygous for the disrupted gene have statistically significant delayed healing of skin wounds and impaired angiogenesis in the granulation tissue. These results indicate that syndecan-4 is an important cell-surface receptor in wound healing and angiogenesis and that syndecan-4 is haplo-insufficient in these processes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Goetinck, PF (reprint author), Massachusetts Gen Hosp East, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA086410, CA69184, R01 CA069184]; NIAMS NIH HHS [T32 AR07098, T32 AR007098]; NICHD NIH HHS [HD-37490, R01 HD037490] NR 25 TC 252 Z9 258 U1 0 U2 13 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2001 VL 107 IS 2 BP R9 EP R14 DI 10.1172/JCI10559 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 393FE UT WOS:000166457900016 PM 11160142 ER PT J AU Perea, S Fothergill, AW Sutton, DA Rinaldi, MG AF Perea, S Fothergill, AW Sutton, DA Rinaldi, MG TI Comparison of in vitro activities of voriconazole and five established antifungal agents against different species of dermatophytes using a broth macrodilution method SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IN-VITRO; FILAMENTOUS FUNGI; AMPHOTERICIN-B; SUSCEPTIBILITIES; ITRACONAZOLE; FLUCONAZOLE; UK-109,496; PATHOGENS; CONIDIA; COMMON AB The in vitro activities of voriconazole against 19 different species of dermatophytes were compared with those of terbinafine, itraconazole, ketoconazole, griseofulvin, and fluconazole. MICs were determined according to a National Committee for Clinical Laboratory Standards broth macrodilution method. Voriconazole appeared more active than ketoconazole, griseofulvin, and fluconazole and less active than itraconazole and terbinafine. Based on these results, voriconazole merits further investigation as a potentially useful agent for the treatment of dermatophytosis. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Perea, S (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA. NR 18 TC 56 Z9 57 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2001 VL 39 IS 1 BP 385 EP 388 DI 10.1128/JCM.39.1.385-388.2001 PG 4 WC Microbiology SC Microbiology GA 393KZ UT WOS:000166468900070 PM 11136808 ER PT J AU Kelly, WK Curley, T Slovin, S Heller, G McCaffrey, J Bajorin, D Ciolino, A Regan, K Schwartz, M Kantoff, P George, D Oh, W Smith, M Kaufman, D Small, EJ Schwartz, L Larson, S Tong, W Scher, H AF Kelly, WK Curley, T Slovin, S Heller, G McCaffrey, J Bajorin, D Ciolino, A Regan, K Schwartz, M Kantoff, P George, D Oh, W Smith, M Kaufman, D Small, EJ Schwartz, L Larson, S Tong, W Scher, H TI Paclitaxel, estramustine phosphate, and carboplatin in patients with advanced prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-I TRIAL; ORAL ESTRAMUSTINE; CLINICAL-TRIALS; OVARIAN-CANCER; PHARMACOKINETICS; VINBLASTINE; COMBINATION; DOCETAXEL; CARCINOMA; ETOPOSIDE AB Purpose: To determine the safety and activity of weekly paclitaxel in combination with estramustine and carboplatin (TEC) in patients with advanced prostate cancer. Patients and Methods: In a dose-escalation study, patients with advanced prostate cancer were administered paclitaxel (weekly 1-hour infusions of 60 to 100 mg/m(2)), oral estramustine(10 mg/kg), and carboplatin (area under the curve, 6 mg/mL-min every 4 weeks). Paclitaxel levels were determined 0, 30, 60, 90, and 120 minutes and 18 hours after infusion, and a concentration-time curve was estimated. Once a safe dose was established, a multi-institutional phase II trial was conducted in patients with progressive androgen-independent disease. Results: Fifty-six patients with progressive androgen-independent disease were treated for a median of four cycles. The dose of paclitaxel was escalated from 60 to 100 mg/m2 without the occurrence of DLT. Posttherapy decreases in serum prostate-specific antigen levels of 50%, 80%, and 90% were seen in 67%, 48%, and 39% (95% confidence interval, 55% to 79%, 35% to 61%, 26% to 52%) of the patients, respectively. Of the 33 patients with measurable disease, two (6%) had a complete response and 13 (39%) had a partial response. The overall median time to progression wets 21 weeks, and the median survival time for all patients was 19.9 months. Major grade 3 or 4 adverse effects were thromboembolic disease (in 25% of patients), hyperglycemia (in 38%), and hypophosphatemia (in 42%). Significant leukopenia, thrombocytopenia, and peripheral neuropathy were not observed. Conclusion: TEC has significant antitumor activity and is well tolerated in patients with progressive androgen-independent prostate cancer. J Clin Oncol 19:44-53. (C) 2001 by American Society of Clinical Oncology. C1 Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor, Genitourinary Oncol Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Nursing, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pharmacol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Clin Chem, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Nucl Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Div Epidemiol & Biostat, New York, NY 10021 USA. Cornell Univ, Joan & Samuel Weill Med Coll, Dept Med, New York, NY USA. Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Med Oncol, Boston, MA USA. Univ Calif San Francisco, Dept Med Oncol, Genitourinary Oncol Serv, San Francisco, CA USA. RP Kelly, WK (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor, Genitourinary Oncol Serv, 1275 York Ave,Box 473, New York, NY 10021 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 32 TC 130 Z9 134 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 44 EP 53 PG 10 WC Oncology SC Oncology GA 389FT UT WOS:000166228500006 PM 11134194 ER PT J AU Clark, JA Wray, NP Ashton, CM AF Clark, JA Wray, NP Ashton, CM TI Living with treatment decisions: Regrets and quality of life among men treated for metastatic prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OF-LIFE; PATIENT SATISFACTION; HEALTH-CARE; OUTCOMES; SCALE AB Purpose: To examine variation in men's long-term regret of treatment decisions, ie, surgical versus chemical castration, for metastatic prostate cancer and its associations with quality of life. Methods: Survey of previously treated patients to assess treatment decisions and quality of life, supplemented with focus groups. Two items addressing whether a patient wished he could change his mind and the belief that he would have been better off with the treatment not chosen were combined in classifying survey respondents as either satisfied or regretful. chi (2) and t tests were used to test associations between regret and treatment history, complications, and quality of life. Results: Survey respondents included 201 men aged 45 to 93 years (median, 71 years), who had begun treatment (71% chemical castration, 29% orchiectomy) a median of 2 years previously, Most reported complications: hot flashes (70%), nausea (34%), and erectile dysfunction (81%). Most were satisfied with the treatment decision, but 23% expressed regret. Regretful men more frequently reported surgical (43%) versus chemical (36%) castration (P = .030) and nausea in the past week (54% v 32%; P = .010) but less frequently reported erectile dysfunction (56% v 72%; P = .048). Regretful men indicated poorer scores on every measure of generic and prostate cancer-related quality of life. Qualitative analyses revealed substantial uncertainty about the progress of their disease and the quality of the decisions in which patients participated. Conclusion: Regret was substantial and associated with treatment choice and quality of life. It may derive from underlying psychosocial distress and problematic communication with physicians when decisions are being reached and over subsequent years. J Clin Oncol 19:72-80. (C) 2001 by American Society of Clinical Oncology. C1 Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Dept Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. RP Clark, JA (reprint author), Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd, Bedford, MA 01730 USA. NR 31 TC 113 Z9 115 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 72 EP 80 PG 9 WC Oncology SC Oncology GA 389FT UT WOS:000166228500009 PM 11134197 ER PT J AU Goldman, DP Schoenbaum, ML Potosky, AL Weeks, JC Berry, SH Escarce, JJ Weidmer, BA Kilgore, ML Wagle, N Adams, JL Figlin, RA Lewis, JH Cohen, J Kaplan, R McCabe, M AF Goldman, DP Schoenbaum, ML Potosky, AL Weeks, JC Berry, SH Escarce, JJ Weidmer, BA Kilgore, ML Wagle, N Adams, JL Figlin, RA Lewis, JH Cohen, J Kaplan, R McCabe, M TI Measuring the incremental cost of clinical cancer research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; TRIALS; CARE; BARRIERS; CHEMOTHERAPY; KNOWLEDGE; ATTITUDES AB Purpose: To summarise evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials. Methods: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from ct randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute-sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental colt. Results: Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs. Conclusion: Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials. J Clin Oncol 19:105-110. (C) 2001 by American Society of Clinical Oncology. C1 RAND Corp, Santa Monica, CA 90407 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD USA. NCI, Div Canc Treatment & Diag, Bethesda, MD USA. NCI, Off Educ & Special Initiat, Bethesda, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Johnson Comprehens Canc Ctr, Los Angeles, CA USA. Agcy Healthcare Res & Qual, Ctr Cost & Financing Studies, Rockville, MD USA. RP Goldman, DP (reprint author), RAND Corp, 1700 Main St, Santa Monica, CA 90407 USA. NR 30 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 105 EP 110 PG 6 WC Oncology SC Oncology GA 389FT UT WOS:000166228500014 PM 11134202 ER PT J AU Tepper, JE O'Connell, MJ Niedzwiecki, D Hollis, D Compton, C Benson, AB Cummings, B Gunderson, L Macdonald, JS Mayer, RJ AF Tepper, JE O'Connell, MJ Niedzwiecki, D Hollis, D Compton, C Benson, AB Cummings, B Gunderson, L Macdonald, JS Mayer, RJ TI Impact of number of nodes retrieved on outcome in patients with rectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOTAL MESORECTAL EXCISION; CIRCUMFERENTIAL MARGIN INVOLVEMENT; SMALL LYMPH-NODES; LOCAL RECURRENCE; COLORECTAL-CARCINOMA; PROGNOSTIC FACTORS; METASTASES; SPECIMENS; ADENOCARCINOMA; RESECTION AB Purpose: We postulated that the pathologic evaluation of the lymph nodes of surgical specimens from patients with rectal cancer can have a substantial impact on time to relapse and survival. Patients and Methods: We analyzed data from 1,664 patients with T3, T4, or node-positive rectal cancer treated in a national intergroup trial of adjuvant therapy with chemotherapy and radiation therapy. Associations between the number of lymph nodes found by the pathologist in the surgical specimen and the time to relapse and survival outcomes were investigated. Results: Patients were divided into groups by nodal status and the corresponding quartiles of numbers of nodes examined. The number of nodes examined was significantly associated with time to relapse and survival among patients who were node-negative. For the first through fourth quartiles, the 5-year relapse rates were 0.37, 0.34, 0.26, and 0.19 (P = .003), and the 5-year survival rates were 0.68, 0.73, 0.72, and 0.82 (P = .02). No significant differences were found by quartiles among patients determined to be node-positive. We propose that observed differences are primarily related to the incorrect determination of nodal status in node-negative patients. Approximately 14 nodes need to be studied to define nodal status accurately. Conclusion: These results suggest that the pathologic assessment of lymph nodes in surgical specimens is often inaccurate and that examining greater number of nodes increases the likelihood of proper staging. Some patients who might benefit fram adjuvant therapy are misclassified as node-negative due to incomplete sampling of lymph nodes. J Clin Oncol 19:157-163. (C) 2001 by American Society of Clinical Oncology. C1 Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Duke Univ, Med Ctr, Canc & Leukemia Grp B, Stat Off, Durham, NC USA. Mayo Clin, Ctr Canc, Rochester, MN USA. Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Northwestern Univ, Div Hematol Oncol, Chicago, IL USA. Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. St Vincents Clin, Ctr Canc, Gastrointestinal Oncol Serv, New York, NY USA. RP Tepper, JE (reprint author), Univ N Carolina, Dept Radiat Oncol, Campus Box 7512, Chapel Hill, NC 27599 USA. NR 28 TC 360 Z9 375 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 157 EP 163 PG 7 WC Oncology SC Oncology GA 389FT UT WOS:000166228500020 PM 11134208 ER PT J AU Hilden, JM Emanuel, EJ Fairclough, DL Link, MP Foley, KM Clarridge, BC Schnipper, LE Mayer, RJ AF Hilden, JM Emanuel, EJ Fairclough, DL Link, MP Foley, KM Clarridge, BC Schnipper, LE Mayer, RJ TI Attitudes and practices among pediatric oncologists regarding end-of-life care: Results of the 1998 American Society of Clinical Oncology survey SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DYING CHILD; PALLIATIVE CARE; CANCER; EUTHANASIA; DEATH; PAIN AB Purpose: In 1998, the American Society of Clinical Oncology (ASCO) surveyed its membership to assess the attitudes, practices, and challenges associated with end-of-life care of patients with cancer. In this report, we summarize the responses of pediatric oncologists and the implications far care of children dying from cancer. Methods: The survey consisted of 118 questions, covering eight categories. All ASCO members in the United States, Canada, and the United Kingdom were mailed a survey, which wets completed by 228 pediatric oncologists, Predictors of particular attitudes and practices were identified using stepwise logistic regression analysis. Potential predictors were age, sex, religious affiliation, importance of religious beliefs, recent death of a relative, specialty, type of practice (rural or urban, academic or nonacademic), amount of time spent in patient care, number of new patients in the past 6 months, and number of patients who died in the past year. Results: Pediatric oncologists reported a lack of formal courses in pediatric palliative care, a strikingly high reliance on trial and error in learning to care for dying children, and a need for strong role models in this area. The lack of an accessible palliative care team or pain service was often identified as ct barrier to good care. Communication difficulties exist between parents and oncologists, especially regarding the shift to end-of-life care and adequate pain control. Conclusion: Pediatric oncologists are working to integrate symptom control, psychosocial support, and palliative care into the routine care of the seriously ill child, although barriers exist that make such comprehensive care a challenge. J Clin Oncol 19:205-212. (C) 2001 by American Society of Clinical Oncology. C1 Childrens Hosp & Clin St Paul, Dept Pediat Hematol Oncol, St Paul, MN 55102 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. AMC Canc Res Ctr, Ctr Res Methodol & Biometr, Denver, CO USA. Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. Mem Sloan Kettering Canc Ctr, Pain & Palliat Care Serv, New York, NY 10021 USA. Univ Massachusetts, Beth Israel Deaconess Med Ctr, Survey Res Ctr, Div Hematol & Oncol, Boston, MA 02125 USA. Dana Farber Canc Inst, Dept Med Adult Oncol, Boston, MA 02115 USA. RP Hilden, JM (reprint author), Childrens Hosp & Clin St Paul, Dept Pediat Hematol Oncol, 345 N Smith Ave, St Paul, MN 55102 USA. NR 33 TC 161 Z9 165 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 205 EP 212 PG 8 WC Oncology SC Oncology GA 389FT UT WOS:000166228500026 PM 11134214 ER PT J AU Lee, SJ Fairclough, D Parsons, SK Soiffer, RJ Fisher, DC Schlossman, RL Antin, JH Weeks, JC AF Lee, SJ Fairclough, D Parsons, SK Soiffer, RJ Fisher, DC Schlossman, RL Antin, JH Weeks, JC TI Recovery after stem-cell transplantation for hematologic diseases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; QUALITY-OF-LIFE; LONG-TERM SURVIVORS; NON-HODGKINS-LYMPHOMA; ACUTE MYELOGENOUS LEUKEMIA; PSYCHOSOCIAL SEQUELAE; FUNCTIONAL STATUS; ADULT SURVIVORS; FOLLOW-UP; HEALTH AB Purpose: Although the number of autologous and allogeneic stem-cell transplantations (SCT) is increasing, relatively little information about recovery after transplantation is available. Quantitative information appropriate for patient counseling is difficult to discern From the literature. We sought to suggest reasonable expectations for recovery and symptoms after SCT for hematologic malignancies and other disorders using the following measures: (1) objective measures of health status, such as frequency of clinic visits, need for rehospitalization, medication usage, work status, and overall and event-free survival; (2) qualitative assessment of quality of life, such as returning to ct normal life, resumption of normal activities, satisfaction with appearance, and whether recovery has occurred; and (3) quantification of specific bothersome symptoms. Patients and Methods: Autologous and allogeneic SCT recipients at a tertiary-care transplant center participated in the prospective, longitudinal questionnaire study. Results: Three hundred twenty patients were studied. Questionnaire response rates at 6, 12, and 24 months range from 85% to 88% among survivors. Although autologous patients had better event-free and overall survival, fewer symptoms, and more complete recovery at 6 months, these advantages had largely equalized by 12 months. Specific bothersome symptoms were reported by less than 24% of patients after transplantation, except for fatigue and financial and sexual difficulties, which were more prevalent. Conclusion: There findings may help counsel patients considering transplantation and educate them about reasonable expectations for recovery. Overall, the low level of bothersome symptoms and continued recovery through the first year after transplantation are encouraging. J Clin Oncol 19:242-252. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Amer Med Ctr, Canc Res Ctr, Denver, CO USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75267-01] NR 43 TC 81 Z9 83 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 242 EP 252 PG 11 WC Oncology SC Oncology GA 389FT UT WOS:000166228500031 PM 11134219 ER PT J AU Rosenbaum, JF AF Rosenbaum, JF TI Introduction - Early onset of antidepressant action SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, ACC 815,15 Parkman St, Boston, MA 02114 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 4 BP 3 EP 3 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 405RP UT WOS:000167173300001 PM 11229786 ER PT J AU Sachs, GS Yan, LJ Swann, AC Allen, MH AF Sachs, GS Yan, LJ Swann, AC Allen, MH TI Integration of suicide prevention into outpatient management of bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Suicide Prevention Intervention CY OCT 24, 2000 CL BOSTON, MASSACHUSETTS ID DEPRESSION; RISK; PSYCHOTHERAPY; SCHIZOPHRENIA; BEHAVIOR AB Suicide prevention is a critical objective in the treatment of bipolar disorder. This article describes practical mechanisms by which monitoring and management of suicide risk can be integrated into the routine care of patients with bipolar disorder. Suicide risk is assessed in terms of inclination (the drive to commit a self-destructive act) and opportunity (access to lethal means). Intervention strategies are adapted to the needs of bipolar patients across 3 phases of treatment: the acute episode; the continuation phase, when symptom reduction has occurred but adaptive recovery has not; and the maintenance phase, in which optimization of adaptive function and vigilance against impending relapse are paramount. Integration of suicide prevention into the outpatient management plan begins with a routine discussion of suicide risk at the initiation of a treatment relationship, even in the absence of other known risk factors. This discussion paves the way for ongoing assessment of suicidality. Just as the recommended routine monitoring of every euthymic bipolar patient includes at least some minimal assessment for prodromal symptoms of acute mania or depression, every clinical visit can include sufficient probes to determine the need for new interventions specific to suicide prevention. Ongoing assessment of risk and protective factors can be linked to a range of individualized interventions designed to meet the varying needs of patients over time. The intensity of monitoring and interventions reflects the clinician's knowledge of risk factors and may be life saving, but it is also important that patients and others involved in their care understand that monitoring cannot guarantee safety. C1 Massachusetts Gen Hosp, Partners Bipolar Treatment Ctr, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Houston, TX USA. Univ Colorado, Hlth Sci Ctr, Colorado Psychiat Hosp, Denver, CO USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Partners Bipolar Treatment Ctr, 50 Staniford St,Suite 580, Boston, MA 02114 USA. RI Allen, Michael/A-8776-2011 NR 42 TC 15 Z9 15 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 25 BP 3 EP 11 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 501MH UT WOS:000172688100001 PM 11765093 ER PT J AU Fava, M AF Fava, M TI Augmentation and combination strategies in treatment-resistant depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; TREATMENT-REFRACTORY DEPRESSION; INDUCED SEXUAL DYSFUNCTION; DOUBLE-BLIND; MAJOR DEPRESSION; LITHIUM-CARBONATE; TRICYCLIC ANTIDEPRESSANTS; BUSPIRONE AUGMENTATION; TRIIODOTHYRONINE AUGMENTATION AB A substantial proportion of depressed patients show only partial or no response to antidepressants, and even among responders to antidepressant treatment, residual symptoms are rather common. When depressions do not respond adequately to treatment with an antidepressant, clinicians may choose to keep the same antidepressant and add another "augmenting" compound. Such augmentation strategies involve the use of a pharmacologic agent that is not considered to be a standard antidepressant but may boost or enhance the effect of an antidepressant. Alternatively, clinicians may choose combination strategies, in which they combine the antidepressant that did not produce adequate response with another antidepressant, typically of a different class. There are only a few controlled clinical trials of these 2 strategies among patients with treatment-resistant depression or among patients who have only partially benefited from antidepressant treatment. Most of the time, clinicians' decisions are, therefore, guided by anecdotal reports, case series, and by some relatively smaller, uncontrolled clinical trials. These augmentation and combination strategies appear to be relatively safe and effective approaches to treatment-resistant depressions, although there is a relative paucity of controlled studies to support their efficacy. These strategies typically aim at obtaining a different neurochemical effect than the one obtained with the antidepressant that has not produced adequate response. While drug-drug interactions may limit the use of some of these strategies, the potential loss of partial benefit from the failed drug inherent in switching may increase the acceptability of augmentation and combination strategies among partial responders. Further studies are clearly needed to evaluate the comparative efficacy and tolerability of these different approaches in treatment-resistant depressions. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. NR 101 TC 115 Z9 119 U1 2 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 18 BP 4 EP 11 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 475HB UT WOS:000171155800002 PM 11575733 ER PT J AU Wirshing, DA AF Wirshing, DA TI Adverse effects of atypical antipsychotics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT International Symposium on Restoring Harmony - Adding Life to Years CY JUN 16-17, 2000 CL SEVILLE, SPAIN ID ONSET DIABETES-MELLITUS; WEIGHT-GAIN; OLANZAPINE; CLOZAPINE; SEROTONIN; OBESITY; QUETIAPINE; GLUCOSE; INSULIN; RAT AB Atypical antipsychotics have the potential to cause weight gain and derangement of glucose metabolism. These side effects can lead to obesity, diabetes mellitus, and dyslipidemia and should be considered in the management of the behavioral and psychological symptoms of dementia. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Wirshing, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 35 TC 37 Z9 40 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 21 BP 7 EP 10 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 478FQ UT WOS:000171332600002 PM 11584988 ER PT J AU Henderson, DC AF Henderson, DC TI Clinical experience with insulin resistance, diabetic ketoacidosis, and type 2 diabetes mellitus in patients treated with atypical antipsychotic agents SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RISPERIDONE TREATMENT; OLANZAPINE TREATMENT; CLOZAPINE TREATMENT; WEIGHT-GAIN; SCHIZOPHRENIA; HYPERGLYCEMIA; PSYCHOSES; EFFICACY; THERAPY AB Numerous reports have associated atypical antipsychotic agents with hyperglycemia, diabetes mellitus, and diabetic ketoacidosis. Although the mechanisms are poorly understood, clinical experience suggests that these adverse effects are major areas of concern and require attention by the psychiatric team and primary care clinicians. This article discusses my clinical experience with glucose metabolism impairment related to treatment with antipsychotic medications. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. NR 39 TC 19 Z9 23 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 27 BP 10 EP 14 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 509PB UT WOS:000173155300003 PM 11806484 ER PT J AU Wozniak, J Biederman, J Richards, JA AF Wozniak, J Biederman, J Richards, JA TI Diagnostic and therapeutic dilemmas in the management of pediatric-onset bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on the Role of Anticonvulsants as Mood Stabilizers CY SEP 22, 2000 CL SSAN ANTONIO, TEXAS ID DEFICIT HYPERACTIVITY DISORDER; CONDUCT DISORDER; JUVENILE MANIA; DOUBLE-BLIND; PREPUBERTAL CHILDREN; REFERRED CHILDREN; CHILDHOOD; SYMPTOMS; LITHIUM; ADHD AB Although the diagnosis of pediatric-onset bipolar disorder is controversial, an increasing literature of systematic research has challenged the traditional view that this disorder is a rare condition. This article summarizes research regarding the atypical presentation of pediatric bipolar disorder and its overlap with attention-deficit/hyperactivity disorder and other comorbid conditions, as well as family-genetic and treatment data. When structured interview data were examined, cases of pediatric mania constituted 16% of referrals to our outpatient clinic. Presentation is atypical by adult standards and includes irritability, chronicity, and mixed state. Family-genetic and treatment data help to establish diagnostic validity. Pediatric bipolar disorder is not a rare condition, Treatment requires a combined pharmacotherapy approach to address issues of comorbidity. Atypical antipsychotic medications have provided promising treatment results, but additional controlled clinical trials are needed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit,Child Psychiat Serv, Boston, MA 02114 USA. RP Wozniak, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit,Child Psychiat Serv, ACC 725,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [R01 MH50657-05] NR 39 TC 45 Z9 45 U1 3 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 14 BP 10 EP 15 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 448RN UT WOS:000169642100003 PM 11469669 ER PT J AU Wirshing, WC AF Wirshing, WC TI Movement disorders associated with neuroleptic treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT International Symposium on Restoring Harmony - Adding Life to Years CY JUN 16-17, 2000 CL SEVILLE, SPAIN ID TOXIN TYPE-B; TARDIVE-DYSKINESIA; OLDER PATIENTS; SCHIZOPHRENIC-PATIENTS; EXTRAPYRAMIDAL SYNDROMES; CERVICAL DYSTONIA; RISPERIDONE; HALOPERIDOL; CLOZAPINE; EFFICACY AB Neuroleptic-induced movement disorders, or extrapyramidal side effects (EPS), can be classified into acute and tardive syndromes. Among the former are parkinsonism, dystonia, and akathisia. Conventional neuroleptics that have traditionally been used to treat psychiatric disorders are often associated with EPS. The newer atypical antipsychotics provide a more-promising treatment strategy for psychiatric disorders and have a lower potential for producing EPS than conventional neuroleptics. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Wirshing, WC (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 36 TC 41 Z9 43 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 21 BP 15 EP 18 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 478FQ UT WOS:000171332600004 PM 11584982 ER PT J AU Frazer, A AF Frazer, A TI Serotonergic and noradrenergic reuptake inhibitors: Prediction of clinical effects from in vitro potencies SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Remission of Anxiety-Related Disorders CY OCT 06, 2000 CL WASHTINGTON, D.C. ID RAT-BRAIN SYNAPTOSOMES; CEREBROSPINAL-FLUID; DEPRESSED-PATIENTS; DORSAL RAPHE; QUANTITATIVE AUTORADIOGRAPHY; 5-HYDROXYTRYPTAMINE RELEASE; ANTAGONIST MIRTAZAPINE; LOCUS-COERULEUS; PLASMA-LEVELS; UPTAKE SITES AB This article reviews the pharmacology of antidepressants, particularly focusing on those that act acutely by blocking the reuptake of norepinephrine (NE) and/or serotonin (5-HT). Such drugs have a very wide range of potencies, measured in vitro, to inhibit the reuptake of these biogenic amines. As a group, the selective serotonin reuptake inhibitors (SSRIs) are the most potent at inhibiting the reuptake of 5-HT Some tricyclic antidepressants (TCAs), such as desipramine and nortriptyline, are much more potent at blocking NE reuptake than 5-HT reuptake, as is the new non-TCA drug reboxetine. Among SSRIs, paroxetine is most potent at blocking the reuptake of NE. When considering whether such potencies measured in vitro translate into pharmacologic effects clinically, it is necessary to know how much drug gets to its site of therapeutic action, presumably the brain. Most, but not all, antidepressants are extensively bound to plasma proteins, and this binding limits considerably the penetration of these drugs across the blood-brain barrier. The amount of drug present in the extracellular fluid (ECF) of brain approximates the non-protein-bound drug concentration in plasma. Comparison of the concentration of antidepressants in ECF with their potencies to inhibit the reuptake of 5-HT and/or NE reveals why some drugs block the reuptake of these biogenic amines in either a selective or nonselective manner. This analysis reveals that venlafaxine may be unique among antidepressants in having a dose-dependent nonselectivity; at low doses it acts primarily as an SSRI, but at higher doses it inhibits the reuptake of NE as well. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Frazer, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr,Mail Code 7764, San Antonio, TX 78229 USA. NR 53 TC 80 Z9 84 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 12 BP 16 EP 23 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 446RJ UT WOS:000169526000004 PM 11430614 ER PT J AU Nierenberg, AA AF Nierenberg, AA TI Long-term management of chronic depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Chronic Major Depression: A Review and Update CY MAY 09, 2000 CL BOSTON, MASSACHUSETTS ID COGNITIVE-BEHAVIORAL TREATMENT; MAJOR DEPRESSION; RECURRENT DEPRESSION; RESIDUAL SYMPTOMS; ANTIDEPRESSANT TREATMENT; MAINTENANCE THERAPIES; DOUBLE-BLIND; DISORDER; RELAPSE; FLUOXETINE AB Untreated major depression tends to either wax and wane, with repeated acute episodes, or persist in a chronic unremitting state, which occurs in up to 35% of depressed patients. After acute remission, those with treated chronic major depression are at high risk of depressive relapse and recurrence. Strategies to reduce the risk of relapse and recurrence include achieving full acute remission, continuing antidepressant treatment with optimal patient adherence, and adding modified cognitive-behavioral psychotherapy. This article will review data relevant to the long-term management of chronic major depression. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Bipoplar Programs, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. NR 36 TC 14 Z9 14 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 6 BP 17 EP 21 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 423HW UT WOS:000168170800004 PM 11310815 ER PT J AU Stahl, SM Nierenberg, AA Gorman, JM AF Stahl, SM Nierenberg, AA Gorman, JM TI Evidence of early onset of antidepressant effect in randomized controlled trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Early Onset of Antidepressant Action CY JAN 12, 2000 CL NEW YORK, NEW YORK ID MILD STRESS MODEL; MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; TRUE DRUG RESPONSE; DOUBLE-BLIND; GENERAL-PRACTICE; PATTERN-ANALYSIS; VENLAFAXINE; CITALOPRAM; FLUOXETINE AB Although antidepressant medications are effective in approximately 70% of patients with major depressive disorder, they have a delayed onset of therapeutic effect. This latency is problematic in that it prolongs the impairments associated with depression, leaves patients vulnerable to an increased risk of suicide, increases the likelihood that a patient will prematurely discontinue therapy, and increases medical costs associated with severe depression. No adequately designed prospective trials have been conducted to evaluate comparative time to onset of antidepressant effect. However, evidence suggests that some antidepressant agents may begin to work faster than others. Citalopram, venlafaxine, and mirtazapine each have exhibited statistically significant differences in some measures of antidepressant action within the first 2 weeks of treatment, both in placebo-controlled trials and in head-to-head comparisons with other antidepressants. This article reviews the data that hint at these drug-specific differences in time to onset of action. Given the potential benefits of early-acting antidepressant treatments, the possibility of superior speed of onset of citalopram venlafaxine, and mirtazapine presented here merits further study in adequately designed, prospective clinical trials. C1 Clin Neurosci Res Ctr, San Diego, CA 92122 USA. Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. New York State Psychiat Inst, Mental Hlth Res Ctr, New York, NY 10032 USA. RP Stahl, SM (reprint author), Clin Neurosci Res Ctr, 8899 Univ Ctr Lane,Suite 130, San Diego, CA 92122 USA. NR 35 TC 53 Z9 58 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 4 BP 17 EP 23 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 405RP UT WOS:000167173300005 PM 11229783 ER PT J AU Pollack, MH AF Pollack, MH TI Optimizing pharmacotherapy of generalized anxiety disorder to achieve remission SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Roundtable Meeting on Defining Remission in Generalized Anxiety Disorder CY JUN 09, 2000 CL ATLANTA, GEORGIA ID VENLAFAXINE EXTENDED-RELEASE; PERIPHERAL DIABETIC NEUROPATHY; RANDOMIZED CONTROLLED TRIAL; PROSPECTIVE FOLLOW-UP; MAJOR DEPRESSION; PANIC DISORDER; DOUBLE-BLIND; CHRONIC PAIN; COGNITIVE THERAPY; NONDEPRESSED OUTPATIENTS AB More than half of patients with generalized anxiety disorder (GAD) have chronic and persistent symptomatology that may warrant ongoing pharmacotherapy. Many of these patients also have significant comorbid mood and anxiety disorders. There is growing consensus among clinicians that the treatment goal for anxiety disorders should be remission, including the minimization of anxiety and depression and resolution of functional impairment. Clinical management strategies for optimizing pharmacotherapy aimed at achieving remission in GAD include attention to drug selection, dosing levels, and duration of treatment. To optimize treatment for GAD with the goal of achieving remission, it is reasonable to select an agent with demonstrated effectiveness for GAD and associated comorbidities as well as a favorable side effect profile. Dosing and duration of treatment should be adequate, and consideration of adjunctive strategies for refractory patients may be warranted. This article discusses the optimization of pharmacotherapy with the goal of promoting remission in patients with GAD. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. NR 92 TC 25 Z9 26 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 19 BP 20 EP 25 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 475RQ UT WOS:000171178600004 PM 11577787 ER PT J AU Allison, DB Casey, DE AF Allison, DB Casey, DE TI Antipsychotic-induced weight gain: A review of the literature SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Weight Gain - A Growing Problem in Schizophrenia Management CY AUG 08, 1999 CL HAMBURG, GERMANY ID BODY-WEIGHT; ATYPICAL ANTIPSYCHOTICS; FLUPHENAZINE DECANOATE; PSYCHIATRIC-PATIENTS; PSYCHOTIC-PATIENTS; DIABETES-MELLITUS; CLINICAL-TRIALS; UNITED-STATES; CLOZAPINE; OLANZAPINE AB With the availability of the so-called novel antipsychotic agents, extrapyramidal symptoms are becoming decreasingly problematic for patients with schizophrenia, and simultaneously, a new symptom is emerging as a preeminent concern. This side effect is weight gain and its metabolic concomitants. This article reviews what is currently known about antipsychotic-induced weight gain, describes the magnitude of the problem, briefly touches on mechanisms of action, and addresses the correlation of interindividual variations in magnitude of weight gain. In addition, we address questions about the effects of weight gain on compliance and whether or not there is a correlation between weight gain and therapeutic efficacy. Finally, we address medical consequences of weight gain and review the literature supporting various treatment options for antipsychotic-induced weight gain. As will be seen, this is an area of research in its infancy, and much work remains to be done. C1 Univ Alabama, Dept Biostat, Birmingham, AL 35295 USA. Columbia Univ, St Lukes Roosevelt Hosp Ctr, Obes Res Ctr, New York, NY USA. Oregon Hlth Sci Univ, Oregon Reg Primate Res Ctr, Portland VA Med Ctr, Portland, OR 97201 USA. RP Allison, DB (reprint author), Univ Alabama, Dept Biostat, 327 Ryals Publ Hlth Bldg,1665 Univ Bldg, Birmingham, AL 35295 USA. OI Allison, David/0000-0003-3566-9399 FU NIDDK NIH HHS [DK51716, DK26687]; NIMH NIH HHS [MH36657] NR 94 TC 429 Z9 452 U1 2 U2 13 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 7 BP 22 EP 31 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 429XL UT WOS:000168543200004 PM 11346192 ER PT J AU Nierenberg, AA AF Nierenberg, AA TI Do some antidepressants work faster than others? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Satellite Symposium on Depression - The Relevance of the Time Factor held at the XXIInd Collegium Internationale Neruo-Psychopharmacologicum Congress CY JUL 09, 2000 CL BRUSSELS, BELGIUM ID MAJOR DEPRESSIVE DISORDER; DOUBLE-BLIND; MIRTAZAPINE; VENLAFAXINE; TOLERABILITY; MELANCHOLIA; PAROXETINE; FLUOXETINE; EFFICACY; ONSET AB The clinical utility of antidepressant drugs is impaired by the delay in onset of their therapeutic action. It is becoming increasingly clear that differences exist between antidepressants with respect to this property, both within and between pharmacologic classes. Post hoc analyses of comparisons between selective serotonin reuptake inhibitors and dual-action antidepressants such as mirtazapine and venlafaxine indicate that the dual-action drugs may have a faster onset of action. At least in the case of mirtazapine, the earlier onset appears to be via a specific antidepressant effect and not an effect on sleep or other accessory symptoms. Studies that compare mirtazapine and venlafaxine are relatively rare and lack sufficient statistical power to determine a difference in the onset of action. Although these differences have been shown in clinical efficacy studies not specifically designed to detect differences in onset of action, a definitive demonstration of early onset of action awaits the results of appropriately designed and powered clinical studies currently planned or in progress. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Biopolar Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,ACC 812, Boston, MA 02114 USA. NR 14 TC 31 Z9 32 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 15 BP 22 EP 25 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 448RT UT WOS:000169642700005 PM 11444763 ER PT J AU Pollack, MH AF Pollack, MH TI Comorbidity, neurobiology, and pharmacotherapy of social anxiety disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Remission of Anxiety-Related Disorders CY OCT 06, 2000 CL WASHTINGTON, D.C. ID CORTICOTROPIN-RELEASING FACTOR; DOUBLE-BLIND; PHOBIA; PLACEBO; PAROXETINE; VENLAFAXINE; DEPRESSION; CLONAZEPAM; PHENELZINE; MECHANISMS AB Social anxiety disorder is a common psychiatric illness that imposes persistent functional impairment and disability on persons who have the disorder. The disorder is characterized by a marked and persistent fear of social or performance situations in which embarrassment may occur. It is the most prevalent of any anxiety disorder and is the third most common psychiatric disorder after depression and alcohol abuse. Social anxiety disorder typically begins during childhood with a mean age at onset between 14 and 16 years and is sometimes preceded by a history of social inhibition or shyness. Persons who have social anxiety disorder either endure or avoid social situations altogether because the fear of embarrassment causes such intense anxiety; such avoidance may ultimately interfere with occupational and/or social functioning and lead to significant disability. The duration of social anxiety disorder is frequently lifelong, and there is a high degree of comorbidity with other psychiatric disorders. Social anxiety disorder is a serious illness that frequently runs a chronic course and is associated with significant morbidity. Patients should be treated aggressively using pharmacotherapeutic agents that can be tolerated over the long term. Cognitive-behavioral therapy should also be considered in treatment planning. Efforts to increase the recognition of social anxiety disorder as a common, distressing, and disabling condition are critical. This article discusses the comorbidity, neurobiology, and pharmacotherapy of social anxiety disorder. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 37 TC 20 Z9 22 U1 2 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 12 BP 24 EP 29 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 446RJ UT WOS:000169526000005 PM 11430615 ER PT J AU Ereshefsky, L Glazer, WM AF Ereshefsky, L Glazer, WM TI Conclusion - Comparison of the bioequivalence of generic versus branded clozapine SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID SCHIZOPHRENIA C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Ereshefsky, L (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 13 TC 8 Z9 8 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 5 BP 25 EP 27 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 422KW UT WOS:000168117900007 PM 11305845 ER PT J AU Pettinati, HM AF Pettinati, HM TI The use of selective serotonin reuptake inhibitors in treating alcoholic subtypes SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Pharmacological Treatment of Alcohol Abuse and Addiction CY FEB 28, 2000 CL PHILADELPHIA, PENNSYLVANIA ID PLACEBO-CONTROLLED TRIAL; DEPRESSED ALCOHOLICS; DOUBLE-BLIND; CONSUMMATORY BEHAVIORS; SERTRALINE TREATMENT; MENTAL-DISORDERS; FLUOXETINE; DEPENDENCE; ETHANOL; TRYPTOPHAN AB The usefulness of selective serotonin reuptake inhibitors (SSRIs) to treat alcohol dependence continues to be a subject of debate. Most recently, investigations have tried to predict whether a given patient will respond to SSRIs in terms of reducing excessive alcohol drinking. The subtyping of alcohol-dependent individuals has ranged from relatively simple classifications (e.g., presence of comorbid depression) to more complex classifications (e.g.,., potential to have abnormalities in serotonin [5-HT] neurotransmission). Although only a few studies have been completed, results thus far indicate that alcoholic subgroups are differentially responsive to 5-HT pharmacotherapy with respect to drinking-related outcomes. In addition, there are preliminary results encouraging the use of SSRIs in combination with other medications for treating alcohol dependence in patients with and without comorbid psychiatric disorders. Information from these studies is promising, suggesting the need for further investigation. C1 Univ Penn, Sch Med, Dept Psychiat, Ctr Study Addict,Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Pettinati, HM (reprint author), Univ Penn, Sch Med, Dept Psychiat, Ctr Study Addict,Philadelphia Vet Affairs Med Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIAAA NIH HHS [R01-AA09544] NR 75 TC 54 Z9 57 U1 4 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 20 BP 26 EP 31 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 478UW UT WOS:000171364600005 PM 11584872 ER PT J AU Nierenberg, AA Gray, SM Grandin, LD AF Nierenberg, AA Gray, SM Grandin, LD TI Mood disorders and suicide SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Suicide Prevention Intervention CY OCT 24, 2000 CL BOSTON, MASSACHUSETTS ID NATIONAL-COMORBIDITY-SURVEY; MAJOR AFFECTIVE-DISORDER; BIPOLAR-II DISORDER; MIXED MANIA; GENERAL-PRACTITIONERS; SUBSTANCE-ABUSE; DYSPHORIC MANIA; RISK-FACTORS; DEPRESSION; BEHAVIOR AB The mood disorders unipolar major depression and bipolar disorder increase the risk of suicidal ideation, attempted suicide, and death by completed suicide. This article reviews the epidemiologic data on the relationship between mood disorders and suicide, with an emphasis on the substantial risk of suicide, while reassessing older data that may no longer apply. Widespread underdiagnosis and undertreatment of major depression and bipolar disorder contribute to an unacceptable risk of suicide, a preventable tragedy. C1 Massachusetts Gen Hosp, Bipolar Programs, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Bipolar Programs, 50 Staniford St,Suite 580, Boston, MA 02114 USA. NR 50 TC 47 Z9 49 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 25 BP 27 EP 30 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 501MH UT WOS:000172688100004 PM 11765092 ER PT J AU Leon, AC Blier, P Culpepper, L Gorman, JM Hirschfeld, RMA Nierenberg, AA Roose, SP Rosenbaum, JF Stahl, SM Trivedi, MH AF Leon, AC Blier, P Culpepper, L Gorman, JM Hirschfeld, RMA Nierenberg, AA Roose, SP Rosenbaum, JF Stahl, SM Trivedi, MH TI An ideal trial to test differential onset of antidepressant effect SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Early Onset of Antidepressant Action CY JAN 12, 2000 CL NEW YORK, NEW YORK ID DOUBLE-BLIND; MAJOR DEPRESSION; CITALOPRAM AB Although various published clinical studies have suggested that some antidepressants may have a more rapid onset of therapeutic effect than others, none of these trials was adequately designed to measure differential time to onset of effect. Thus, existing data do not support claims that one drug reduces the symptoms of depression faster than another. in this article, we propose a study that would be ideal for measuring comparative onset of antidepressant effect. The key features of this ideal trial include (1) a prospective definition of early onset of action, (2) increased frequency of assessment, (3) a data-analytic approach capable of capturing the dynamic nature of symptomatic change, and (4) various strategies to minimize bias and heterogeneity of response. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Clin Neurosci Res Ctr, San Diego, CA USA. Univ Texas, Med Branch, Dept Psychiat, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Behav Sci, Galveston, TX 77550 USA. Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Clin Psychopharmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Outpatient Psychiat, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Family Med, Boston, MA 02118 USA. Univ Florida, Inst Brain, Dept Psychiat, Gainesville, FL USA. New York State Psychiat Inst, New York, NY 10032 USA. Cornell Univ, Weill Med Coll, Dept Biostat Psychiat, New York, NY 10021 USA. RP Leon, AC (reprint author), Cornell Univ, Weill Med Coll, Dept Psychiat, Box 140,525 E 68th St, New York, NY 10021 USA. NR 6 TC 24 Z9 26 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 4 BP 34 EP 36 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 405RP UT WOS:000167173300008 PM 11229787 ER PT J AU Hirschfeld, RMA Nierenberg, AA Gorman, JM Roose, SP Leon, AC Blier, P Culpepper, L Rosenbaum, JF Stahl, SM Trivedi, MH AF Hirschfeld, RMA Nierenberg, AA Gorman, JM Roose, SP Leon, AC Blier, P Culpepper, L Rosenbaum, JF Stahl, SM Trivedi, MH TI Debate and discussion - Do some antidepressants have a faster onset of action than others? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID LITHIUM AUGMENTATION; CONTROLLED TRIAL; DEPRESSION; FLUOXETINE C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. New York State Psychiat Inst, New York, NY 10032 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Univ Florida, Inst Brain, Gainesville, FL USA. Boston Univ, Sch Med, Dept Family Med, Boston, MA 02118 USA. Clin Neurosci Res Ctr, San Diego, CA USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. RP Hirschfeld, RMA (reprint author), Univ Texas, Med Branch, Galveston, TX 77550 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 4 BP 37 EP 40 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 405RP UT WOS:000167173300009 ER PT J AU Henderson, DC AF Henderson, DC TI Clozapine: Diabetes mellitus, weight gain, and lipid abnormalities SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Effects of Drugs on Body Weight and Glucose Regulation CY DEC 16, 2000 CL NEW YORK, NEW YORK ID INSULIN-DEPENDENT DIABETICS; IMPAIRED GLUCOSE-TOLERANCE; CARBOHYDRATE-METABOLISM; SCHIZOPHRENIC-PATIENTS; OLANZAPINE TREATMENT; KETOACIDOSIS; OBESITY; HYPERGLYCEMIA; PREVALENCE; DISORDERS AB Clozapine remains the most effective agent for treatment-resistant patients with schizophrenia, Recently, treatment with clozapine has been linked to a number of metabolic disturbances, including weight gain, diabetes mellitus, and serum lipid abnormalities. Despite the potential risks of medical morbidities, clozapine continues to have a major role in the care of treatment-resistant patients with schizophrenia. This article discusses the diagnosis and significance of the above metabolic abnormalities and potential mechanisms for these abnormalities as well as recommendations for monitoring and treatment. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066] NR 48 TC 52 Z9 56 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 23 BP 39 EP 44 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 482YN UT WOS:000171605000006 PM 11603884 ER PT J AU Pitman, RK Shin, LM Rauch, SL AF Pitman, RK Shin, LM Rauch, SL TI Investigating the pathogenesis of posttraumatic stress disorder with neuroimaging SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Advisory Board Meeting on Understanding Posttraumatic Stress Disorder CY MAR 08-09, 1999 CL CANNES, FRANCE ID POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL ABUSE; SCRIPT-DRIVEN IMAGERY; CEREBRAL BLOOD-FLOW; HIPPOCAMPAL VOLUME; MAJOR DEPRESSION; COMBAT VETERANS; BRAIN; MEMORY; PTSD AB Rapidly evolving brain neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) Eire proving fruitful in exploring the pathogenesis and pathophysiology of posttraumatic stress disorder (PTSD). Structural abnormalities in PTSD found with MRI include nonspecific white matter lesions and decreased hippocampal volume. These abnormalities may reflect pretrauma vulnerability to develop PTSD, or they may be a consequence of traumatic exposure, PTSD, and/or PTSD sequelae. Functional neuroimaging symptom provocation and cognitive activation paradigms using PET measurement of regional cerebral blood flow have revealed greater activation of the amygdala and anterior paralimbic structures (which are known to be involved in processing negative emotions such as fear), greater deactivation of Broca's region (motor speech) and other nonlimbic cortical regions, and failure of activation of the cingulate cortex (which possibly plays an inhibitory role) in response to trauma- related stimuli in individuals with PTSD. Functional MRI research has shown the amygdala to be hyperresponsive to fear-related stimuli in this disorder. Research with PET suggests that cortical, notably hippocampal, metabolism is suppressed to a greater extent by pharmacologic stimulation of the noradrenergic system in persons with PTSD. The growth of knowledge concerning the anatomical and neurochemical basis of this important mental disorder will hopefully eventually lead to rational psychological and pharmacologic treatments. C1 VA Res Serv, Manchester, NH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Pitman, RK (reprint author), PTSD Res Lab, MGH-East,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 44 TC 140 Z9 143 U1 6 U2 21 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 17 BP 47 EP 54 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 460NF UT WOS:000170313100009 PM 11495097 ER PT J AU Gray, SM Otto, MW AF Gray, SM Otto, MW TI Psychosocial approaches to suicide prevention: Applications to patients with bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Suicide Prevention Intervention CY OCT 24, 2000 CL BOSTON, MASSACHUSETTS ID RANDOMIZED CONTROLLED TRIAL; SELF-POISONING PATIENTS; MAJOR DEPRESSION; DYSFUNCTIONAL ATTITUDES; CONTROLLED INTERVENTION; SECONDARY PREVENTION; FOLLOW-UP; HOPELESSNESS; IDEATION; RISK AB Hopelessness, dysfunctional attitudes, and poor problem-solving abilities are psychosocial risk factors that have been identified as predictors of suicide. These psychosocial risk factors may help clinicians apply specific therapies and treatments to patients with bipolar disorder at risk for suicide. A search of the literature on suicide prevention revealed 17 randomized, controlled studies, which the authors reviewed to determine the efficacy of strategies aimed at eliminating psychosocial risk factors for suicide. Three strategies emerged as efficacious: (1) applying interventions to elicit emergency care by patients at times of distress; (2) training in problem-solving strategies; and (3) combining comprehensive interventions that include problem solving with intensive rehearsal of cognitive, social, emotional-labeling, and distress-tolerance skills. On the basis of their review of the literature, the authors make recommendations for suicide prevention for patients with bipolar disorder. C1 Massachusetts Gen Hosp, Partners Bipolar Treatment Ctr, Boston, MA 02114 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Partners Bipolar Treatment Ctr, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 51 TC 28 Z9 28 U1 7 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 25 BP 56 EP 64 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 501MH UT WOS:000172688100009 PM 11765098 ER PT J AU Nierenberg, AA DeCecco, LM AF Nierenberg, AA DeCecco, LM TI Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: A focus on treatment-resistant depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIOR-THERAPY; PROSPECTIVE FOLLOW-UP; MAJOR DEPRESSION; RESIDUAL SYMPTOMS; RECURRENT DEPRESSION; SYMPTOMATOLOGY IDS; RELAPSE; DISORDER; RECOVERY; PREVENTION AB Multiple definitions have been used to characterize the outcome of treatments for depression. Beyond the simple criterion of a statistically significant improvement in depression rating scale scores, researchers have had to use more clinically relevant categorical outcomes: response (without remission), remission, nonresponse, partial response, relapse, recurrence, recovery, and, more recently, depressive breakthrough. This article reviews the definitions of these terms and their relevance for the study of treatment-resistant depression. C1 Massachusetts Gen Hosp, Depress Res Program, Clin Psychopharmcol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Bipolar Programs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Res Program, Clin Psychopharmcol Unit, 15 Parkman St, Boston, MA 02114 USA. NR 41 TC 17 Z9 17 U1 2 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 16 BP S5 EP S9 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 458MV UT WOS:000170198900002 ER PT J AU Kamolmatyakul, S Chen, W Li, YP AF Kamolmatyakul, S Chen, W Li, YP TI Interferon-gamma down-regulates gene expression of cathepsin K in osteoclasts and inhibits osteoclast formation SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE interferon-gamma; cathepsin K; osteoclast formation; gene regulation ID NEONATAL MOUSE CALVARIA; BONE-RESORPTION; NORMAL MICE; INTERLEUKIN-1; CELLS AB The cytokine, IFN-gamma, has been shown in vitro to inhibit bone resorption, but the mechanisms responsible for this inhibition have not been clearly defined. Cathepsin K is a major protease responsible for bone resorption. IFN-gamma may inhibit bone resorption through down-regulation of osteoclast genes, including cathepsin K. To test the hypothesis, we investigated the effect of IFN-gamma on cathepsin K expression in the MOCP-5 and wild-type mouse bone marrow co-culture systems by Northern blot as well as osteoclast formation at different stages of differentiation. The results show that IFN-gamma down-regulates mRNA levels of cathepsin K in a time- and dose-dependent manner. Consequently, cathepsin K protein production is also reduced by IFN-gamma. Moreover, our results indicate that IFN-gamma inhibits osteoclast formation only early in osteoclast differentiation. IL-6 and TNF alpha did not significantly affect cathepsin K gene expression in osteoclasts. However, IL-1 alpha stimulated gene expression, in conclusion, our data suggest that the actions of IFN-gamma on osteoclastic bone resorption may be mediated by its effects on both osteoclast formation at an early stage and osteoclast gene expression in mature osteoclasts. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02135 USA. Forsyth Inst, Harvard Forsyth Dept Oral Biol, Boston, MA 02135 USA. Harvard Univ, Sch Dent Med, Boston, MA 02135 USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02135 USA. FU NIAMS NIH HHS [AR 44741]; NIDCR NIH HHS [DE-10887] NR 21 TC 33 Z9 35 U1 0 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JAN PY 2001 VL 80 IS 1 BP 351 EP 355 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 432HT UT WOS:000168686700010 PM 11269728 ER PT J AU Filbin, MR Mylonakis, EE Callegari, L Legome, E AF Filbin, MR Mylonakis, EE Callegari, L Legome, E TI Babesiosis SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE tick; babesiosis ID UNITED-STATES; TRANSFUSION; ATOVAQUONE; DISEASES AB A case of human babesiosis is presented, This case emphasizes the need to consider tick-borne disease in anyone who presents with Prolonged and undulating fevers, chills, headache, myalgias, and arthralgias. This holds true particularly in areas endemic for tick-borne diseases, even in the absence of a history of tick bite. These symptoms, associated with signs of Intravascular hemolysis, thrombo-cytopenia, and renal insufficiency in a patient who resides in, or with recent travel to, the Northeastern United States, strongly suggest a diagnosis of babesiosis. (C) 2001 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Filbin, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, 55 Fruit St,Founders 150, Boston, MA 02114 USA. NR 21 TC 4 Z9 4 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2001 VL 20 IS 1 BP 21 EP 24 DI 10.1016/S0736-4679(00)00289-4 PG 4 WC Emergency Medicine SC Emergency Medicine GA 397MH UT WOS:000166699100004 PM 11165832 ER PT J AU Reisner, AT Binder, WD Nadel, ES Brown, DFM AF Reisner, AT Binder, WD Nadel, ES Brown, DFM TI Complicated acute myocardial infarction SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ORBITAL HEMORRHAGE; VENTRICULAR-TACHYCARDIA; TRIAL; DEFIBRILLATION; THROMBOLYSIS; LIDOCAINE; TRAUMA; AGENTS C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Affiliated Emergency Med Residency, Div Emergency Med, Boston, MA 02138 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2001 VL 20 IS 1 BP 73 EP 79 DI 10.1016/S0736-4679(00)00291-2 PG 7 WC Emergency Medicine SC Emergency Medicine GA 397MH UT WOS:000166699100013 PM 11165841 ER PT J AU Hellman, J Warren, HS AF Hellman, J Warren, HS TI Outer membrane protein A (OmpA), peptidoglycan-associated lipoprotein (PAL), and murein lipoprotein (MLP) are released in experimental Gram-negative sepsis SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article ID ESCHERICHIA-COLI J5; TOLL-LIKE RECEPTOR-2; HUMAN SEPTIC SHOCK; BACTERIA; LIPOPOLYSACCHARIDE; ENDOTOXEMIA; ANTIBODIES; ANTISERUM; SERUM; MODEL AB We previously showed that Escherichia coli bacteria incubated in normal human serum release complexes that contain three conserved Gram-negative bacterial outer membrane proteins (OMPs) and LPS. We have identified the OMPs as outer membrane protein A (OmpA), peptidoglycan-associated lipoprotein (PAL), and murein lipoprotein (MLP). These OMPs are conserved among enteric Gramnegative bacteria and are bound by IgG in antisera raised to heat-killed rough bacteria such as E. coli J5 (J5 IgG). The present experiments were performed to further analyze the release of these OMPs in a rat wound infection model of sepsis. Plasma was collected from thermally injured rats with E. coli O18 sepsis and filtered. LPS was affinity-purified from plasma filtrates using monoclonal antibody specific for the O-polysaccharide side chain of E. coli O18 LPS. Plasma filtrates were also incubated with J5 IgG conjugated to magnetic beads. Affinity-purified samples were analyzed for the OMPs by immunoblotting. OmpA, PAL, and MLP were released into septic rat blood in complexes with LPS. PAL was consistently present in samples affinity-purified using J5 IgG. The results indicate that OmpA, PAL, and MLP are released and circulate in experimental Gram-negative sepsis and suggest that a proportion of released OMPs are tightly associated with LPS. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hellman, J (reprint author), Massachusetts Gen Hosp, CNY, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02445 USA. FU NIAID NIH HHS [AI 01722-01]; NIGMS NIH HHS [GM 59694-01A1] NR 26 TC 18 Z9 19 U1 0 U2 3 PU W S MANEY & SONS LTD PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 2001 VL 7 IS 1 BP 69 EP 72 DI 10.1179/096805101101532477 PG 4 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 441WG UT WOS:000169252100010 PM 11521086 ER PT J AU Bernheiden, M Heinrich, JM Minigo, G Schutt, C Stelter, F Freeman, M Golenbock, D Jack, RS AF Bernheiden, M Heinrich, JM Minigo, G Schutt, C Stelter, F Freeman, M Golenbock, D Jack, RS TI LBP, CD14, TLR4 and the murine innate immune response to a peritoneal Salmonella infection SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article; Proceedings Paper CT 6th Conference of the International-Endotoxin-Society CY AUG 24-27, 2000 CL PARIS, FRANCE SP Int Endotoxin Soc ID LPS-BINDING-PROTEIN; NATURAL-RESISTANCE; LIPOPOLYSACCHARIDE LPS; SOLUBLE CD14; MEMBRANE AB In mice, defense against an intraperitoneal Salmonella infection depends on a vigorous innate immune response, Mutations which lead to an inadequate early response to the pathogen thus identify genes involved in innate immunity. The best studied host resistance factor, NRAMP-1, is an endosomal membrane protein whose loss leads to an inability of the animals to hold the infection in check. However, innate defense against Salmonella is not restricted to mechanisms which directly attack the pathogen within macrophages. Here we have examined the contribution of the LBP, CD14 and TLR4 gene products to innate defense against Salmonella. To this end, we have generated mice which carry a wild-type allele of NRAMP-1, but which are deficient for the LBP, CD14 or TLR4 genes. Loss of any of these genes leads to a susceptibility to Salmonella as dramatic as that seen in animals lacking functional NRAMP-1 protein. This indicates that LBP, CD14 and TLR4 are all critical elements required in the proper induction of this innate defense system. C1 Univ Klinikum Greifswald, Inst Immunol & Transfus Med, D-17489 Greifswald, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Jack, RS (reprint author), Univ Klinikum Greifswald, Inst Immunol & Transfus Med, D-17489 Greifswald, Germany. FU NHLBI NIH HHS [HL 45098, HL 56985]; NIDDK NIH HHS [DK 50305] NR 10 TC 57 Z9 58 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 2001 VL 7 IS 6 BP 447 EP 450 DI 10.1179/096805101101533061 PG 4 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 508LR UT WOS:000173090700006 PM 11753215 ER PT J AU Bounds, BC Brugge, WR AF Bounds, BC Brugge, WR TI EUS diagnosis of cystic lesions of the pancreas SO JOURNAL OF GASTROINTESTINAL CANCER LA English DT Review ID MUCINOUS DUCTAL ECTASIA; INTRADUCTAL PAPILLARY NEOPLASMS; DIFFERENTIAL-DIAGNOSIS; SOLID TUMORS; CYSTADENOMA; MALIGNANCY AB Background. Cystic tumors of the pancreas are composed of benign, premalignant, malignant, and inflammatory lesions that are traditionally difficult to diagnose. Most of the tumors are initially detected on CT/US scanning, but often the morphological characteristics are insufficient for making a definitive diagnosis. Endoscopic ultrasound (EUS) may be an ideal tool for imaging of these lesions because it can provide highly detailed imaging without interference by bowel or air. Furthermore, EUS can direct fine needle aspiration of the lesions, providing cyst fluid for cytologic examination. The findings of cyst fluid cytology can be complemented by the use of cyst fluid tumor maker, such as CEA, Using the morphologic appearance by endosonography, the results of cytology, and tumor marker analysis, EUS can often differentiate between benign, malignant, and inflammatory cystic lesions of the pancreas. C1 Massachusetts Gen Hosp, Blake 4 GI Unit, Boston, MA 02114 USA. RP Bounds, BC (reprint author), Massachusetts Gen Hosp, Blake 4 GI Unit, 55 Fruit St, Boston, MA 02114 USA. NR 27 TC 16 Z9 18 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1941-6628 EI 1941-6636 J9 J GASTROINTEST CANC JI J. Gastrointest. Canc. PY 2001 VL 30 IS 1-2 BP 27 EP 31 DI 10.1385/IJGC:30:1-2:027 PG 5 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA 628KL UT WOS:000179993800004 PM 12489578 ER PT J AU Blumenthal, D Bass, EB AF Blumenthal, D Bass, EB TI The need for data not dogma on the costs of graduate medical education SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Partners HealthCare Syst, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2001 VL 16 IS 1 BP 66 EP 67 DI 10.1111/j.1525-1497.2001.01105.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 402HA UT WOS:000166979600009 PM 11251752 ER PT J AU Jensen, MOJ Lemmon, JD Gessaghi, VC Conrad, CP Levine, RA Yoganathan, AP AF Jensen, MOJ Lemmon, JD Gessaghi, VC Conrad, CP Levine, RA Yoganathan, AP TI Harvested porcine mitral xenograft fixation: Impact on fluid dynamic performance SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID IN-VITRO; CROSS-LINKING; GLUTARALDEHYDE FIXATION; ANNULAR DILATATION; VALVE REPLACEMENT; TISSUE; REGURGITATION; MORPHOLOGY; MECHANICS; RELEVANCE AB Background and aim of the study: Recent developments suggest that stentless bioprosthetic mitral valve heterografts should be considered in order to optimize valve hydrodynamics. The fixation process alters the mechanical properties of tissue. This study investigates the changes in mitral valve morphology and hemodynamic performance following fixation. Methods: Porcine mitral valves were excised and attached to a physiological annular ring. Mitral valve function was studied in vitro with a rigid transparent left heart model, allowing transverse and sagittal views. Initial experiments were performed with fresh valves under physiological conditions. Three different papillary muscle positions were used, and each was recorded. After glutaraldehyde fixation, genipin fixation, and cryopreservation, the valves were re-studied while maintaining cardiac output. Performance characteristics before and after fixation were obtained from hydrodynamic pressure and flow data, high-speed video camera, digital video, Doppler ultrasound, and three-dimensional papillary muscle force measurements. Morphology changes were detected by detailed anatomic measurements of the valves before and after fixation. Results: Valve length was reduced by 18.5% after fixation with genipin (p <0.001), but not with glutaraldehyde. Cryopreserved valves showed no statistically significant changes in morphology or hydrodynamic performance after preservation. The forward flow opening area was reduced by 12.2% (p <0.001) after glutereldehyde fixation, and by 32.3% (p = 0.004) after genipin fixation. Thus, maximal forward flow velocity was increased by 33.3% (p 0.008) after glutaraldehyde fixation and by 52.8% (p = 0.001) after genipin fixation. The flow acceleration was consistent with a funnel shape of the fixed valves causing important flow contraction beyond the orifice (vena contracta). The papillary muscle force increased with epically posterior papillary muscle displacement by 20.4% (p = 0.001) and 101.5% (p <0.001) after glutaraldehyde and genipin fixation, respectively, and total regurgitant volume was increased by 91.6% (p <0.001) and 117.3% (p <0.001), respectively. The work required by the heart simulator to maintain a constant cardiac output at constant vascular resistance increased by 24.2% (p = 0.003) and 34.2% (p = 0.004) after glutaraldehyde and genipin fixation, respectively. Conclusion: The present study shows that chemical fixation of porcine mitral valves adversely affects the hemodynamics of the valves, increasing overall workload. The effects were more severe after fixation with genipin than with glutaraldehyde. This suggests the need to explore other fixation agents to optimize valvular cardiac function. Cryopreservation had no detrimental effects on valvular hemodynamic performance. C1 Emory Sch Biomed Engn, Georgia Inst Technol, Atlanta, GA 30332 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yoganathan, AP (reprint author), Emory Sch Biomed Engn, Georgia Inst Technol, 315 Ferst Dr, Atlanta, GA 30332 USA. FU NHLBI NIH HHS [HL52009] NR 39 TC 14 Z9 14 U1 0 U2 1 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD, ENGLAND HA6 2ET SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD JAN PY 2001 VL 10 IS 1 BP 111 EP 124 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 393FC UT WOS:000166457700018 PM 11206757 ER PT J AU Faunce, DE Sonoda, KH Stein-Streilein, J AF Faunce, DE Sonoda, KH Stein-Streilein, J TI MIP-2 recruits NKT cells to the spleen during tolerance induction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNE DEVIATION ACAID; KILLER T-CELLS; ANTERIOR-CHAMBER; DENDRITIC CELLS; ORAL TOLERANCE; B-CELLS; EXPRESSION; CHEMOKINES; ANTIGEN; RECEPTOR AB Peripheral tolerance occurs after intraocular administration of Ag and is dependent on an increase in splenic NKT cells. New data here show that macrophage inflammatory protein-2 (MIP-2) is selectively up-regulated in tolerance-conferring APCs and serves to recruit NKT cells to the splenic marginal zone, where they form clusters with APCs and T cells. In the absence of the high-affinity receptor for MIP-2 las in CXCR2-deficient mice) or in the presence of a blocking Ab to MIP-2, peripheral tolerance is prevented, and Ag-specific T regulatory cells are not generated. Understanding the regulation of lymphocyte traffic during tolerance induction may lead to novel therapies for autoimmunity, graft acceptance, and tumor rejection. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, NEI, Training Program Mol Bases Eye Dis, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Pulm & Crit Care, Boston, MA 02115 USA. RP Stein-Streilein, J (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NEI NIH HHS [EY11983-02, EY07021-02, T32EY07145] NR 34 TC 127 Z9 131 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 JAN 1 PY 2001 VL 166 IS 1 BP 313 EP 321 PG 9 WC Immunology SC Immunology GA 385PG UT WOS:000166012400040 PM 11123307 ER PT J AU Lewinsohn, DM Zhu, LQ Madison, VJ Dillon, DC Fling, SP Reed, SG Grabstein, KH Alderson, MR AF Lewinsohn, DM Zhu, LQ Madison, VJ Dillon, DC Fling, SP Reed, SG Grabstein, KH Alderson, MR TI Classically restricted human CD8(+) T lymphocytes derived from Mycobacterium tuberculosis-infected cells: Definition of antigenic specificity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN ANTIGENS; BOVIS BCG; RESPONSES; MICE; VACCINATION; IMMUNITY; CLONING; ESAT-6; CD4(+); CLONES AB Previous studies in murine and human models have suggested an important role for HCA Ia-restricted CD8(+) T cells in host defense to Mycobacterium tuberculosis (Mtb), Therefore, understanding the Ags presented via HLA-Ia will be important in understanding the host response to Mtb and in rational vaccine design, We have used monocyte-derived dendritic cells in a limiting dilution analysis to generate Mtb-specific CD8(+) T cells. Two HLA-Ia-restricted CD8(+) T cell clones derived by this method were selected for detailed analysis. One was HLA-B44 restricted, and the other was HLA-B14 restricted. Both were found to react with Mtb-infected, but not bacillus Calmette-Guerin-infected, targets. For both these clones, the Ag was identified as culture filtrate protein 10 (CFP10)/Mtb11, a 10.8-kDa protein not expressed by bacillus Calmette-Guerin. Both clones were inhibited by the anti-class I Ab and anti-HLA-B,C Abs, Using a panel of CFP10/Mtb11-derived 15-aa peptides overlapping by 11 aa, the region containing the epitopes for both clones has been defined. Minimal IO-aa epitopes were defined for both clones. CD8(+) effector cells specific for these two epitopes are present at high frequency in the circulating pool. Moreover, the CD8(+) T cell response to CFP10/Mtb11 can be largely accounted for by the two epitopes defined herein, suggesting that this is the immunodominant response for this purified protein derivative-positive donor. This study represents the first time CD8(+) T cells generated against Mtb-infected APC have been used to elucidate an Mtb-specific CD8(+) T cell Ag. C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Pulm & Crit Care Med, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97207 USA. Corixa Corp, Seattle, WA 98104 USA. RP Lewinsohn, DM (reprint author), Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Pulm & Crit Care Med, 3710 US Vet Rd, Portland, OR 97207 USA. RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NIAID NIH HHS [1K08AI01644, N01AI75320] NR 37 TC 75 Z9 76 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2001 VL 166 IS 1 BP 439 EP 446 PG 8 WC Immunology SC Immunology GA 385PG UT WOS:000166012400055 PM 11123322 ER PT J AU Rao, A Solymar, DC Lee, DU Agarwal, S AF Rao, A Solymar, DC Lee, DU Agarwal, S TI Regulation of cytokine gene expression during T cell differentiation. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 3 BP 19 EP 19 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200004 ER PT J AU Goldfeld, AE Barthel, R Tsytsykova, AV Barczak, AK AF Goldfeld, AE Barthel, R Tsytsykova, AV Barczak, AK TI TNF-alpha gene regulation in LPS or mycobacteria-stimulated monocytes is dependent upon the assembly of a unique enhanceosome and CBP/p300 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 18 BP 22 EP 22 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200019 ER PT J AU Runkel, L Kuo, F Rennert, P Chicheportiche, Y Tschopp, J Browning, JL AF Runkel, L Kuo, F Rennert, P Chicheportiche, Y Tschopp, J Browning, JL TI Null mutation of the TNF family member, APRIL, results in embryonic lethality and cardiac defects SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Biogen Inc, Cambridge, MA 02142 USA. Dana Farber Canc Ctr, Boston, MA USA. CMU, Geneva, Switzerland. Univ Lausanne, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 30 BP 25 EP 25 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200031 ER PT J AU Tsytsykova, AV Barthel, R Goldfeld, AE AF Tsytsykova, AV Barthel, R Goldfeld, AE TI Inducer-specific enhanceosome formation controls TNF-alpha gene expression in T lymphocytes SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 137 BP 50 EP 50 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200137 ER PT J AU Re, F Jack, L Strominger, Y AF Re, F Jack, L Strominger, Y TI Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 195 BP 63 EP 63 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200195 ER PT J AU Sivakumar, PV Glaccum, M Kennedy, M Bevan, M Benoist, C Mathis, D Butz, E Goldrath, A AF Sivakumar, PV Glaccum, M Kennedy, M Bevan, M Benoist, C Mathis, D Butz, E Goldrath, A TI IL-7 and IL-15 are essential for the proliferation and survival of memory CD8 T cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Washington, Seattle, WA 98195 USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 357 BP 101 EP 101 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200356 ER PT J AU Appleman, LJ Tzachanis, D Grader-Beck, T van Puijenbroek, AAFL Boussiotis, VA AF Appleman, LJ Tzachanis, D Grader-Beck, T van Puijenbroek, AAFL Boussiotis, VA TI Helper T cell anergy: from biochemistry to cancer pathophysiology and therapeutics SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE anergy; tolerance; costimulation; T cells ID PROTEIN-TYROSINE PHOSPHORYLATION; ALLOANTIGEN-SPECIFIC TOLERANCE; KINASE SIGNALING PATHWAYS; CYCLIN-DEPENDENT KINASES; LONG-TERM ACCEPTANCE; VERSUS-HOST DISEASE; GROWTH-FACTOR-BETA; CLONAL ANERGY; IN-VIVO; IL-2 GENE AB Tolerance in vivo and its in vitro counterpart, anergy, are defined as the state in which helper T lymphocytes are alive but incapable of producing IL-2 and expanding in response to optimal antigenic stimulation. Anergy is induced when the T cell receptor (TCR) is engaged by antigen in the absence of costimulation or IL-2. This leads to unique intracellular signaling events that stand in contrast to those triggered by coligation of the TCR and costimulatory receptors. Specifically, anergy is characterized by lack of activation of lck, ZAP 70, Ras, ERK, JNK, AP-1, and NF-AT. In contrast, anergizing stimuli appear to activate the protein tyrosine kinase fyn, increase intracellular calcium levels, and activate Rap1. Moreover, anergizing TCR signals result in increased intracellular concentrations of the second messenger cAMP. This second messenger upregulates the cyclin-dependent kinase (cdk) inhibitor p27(kip1), sequestering cyclin D2-cdk4, and cyclin E/cdk2 complexes and preventing progression of T cells through the G(1) restriction point of the cell cycle. In contrast, costimulation through CD28 prevents p27(kip1) accumulation by decreasing the levels of intracellular cAMP and promotes p27(kip1) downregulation due to direct degradation of the protein via the ubiquitin-proteasome pathway. Subsequent autocrine action of IL-2 leads to further degradation of p27(kip1) and entry into S phase. Understanding the biochemical and molecular basis of T cell anergy will allow the development of new assays to evaluate the immune status of patients in a variety of clinical settings in which tolerance has an important role, including cancer, autoimmune diseases, and organ transplantation. Precise understanding of these biochemical and molecular events is necessary in order to develop novel treatment strategies against cancer. One of the mechanisms by which tumors downregulate the immune system is through the anergizing inactivation of helper T lymphocytes, resulting in the absence of T cell help to tumor-specific CTLs. Although T-cells specific for tumor associated antigens are detected in cancer patients they often are unresponsive. Reversal of the defects that block the cell cycle progression is mandatory for clonal expansion of tumor specific T cells during the administration of tumor vaccines. Reversal of the anergic state of tumor specific T cells is also critical for the sufficient expansion of such T cells ex vivo for adoptive immunotherapy. On the other hand, understanding the molecular mechanisms of anergy will greatly improve our ability to design novel clinical therapeutic approaches to induce antigen-specific tolerance and prevent graft rejection and graft-versus-host disease. Such treatment approaches will allow transplantation of bone marrow and solid organs between individuals with increasing HLA disparity and therefore expand the donor pool, enable reduction in the need for nonspecific immunosuppression, minimize the toxicity of chemotherapy, and reduce the risk of opportunistic infections. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Dana Farber Canc Inst, Mayer 547,44 Binney St, Boston, MA 02115 USA. OI Appleman, Leonard/0000-0003-4951-7388 FU NHLBI NIH HHS [HL 54785]; NIAID NIH HHS [AI 41584, AI 43552] NR 104 TC 40 Z9 42 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PY 2001 VL 78 IS 12 BP 673 EP 683 DI 10.1007/s001090000180 PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 409WH UT WOS:000167408300004 PM 11434720 ER PT J AU Bohning, DE He, L George, MS Epstein, CM AF Bohning, DE He, L George, MS Epstein, CM TI Deconvolution of transcranial magnetic stimulation (TMS) maps SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE transcranial magnetic stimulation; cerebral cortex; brain mapping; deconvolution; motor cortex ID HUMAN MOTOR CORTEX; HUMAN CEREBRAL-CORTEX; BRAIN-STIMULATION; HAND MUSCLE; EXCITATION; DEPRESSION; REPRESENTATION; CONNECTIVITY; MODULATION; RESPONSES AB Transcranial magnetic stimulation (TMS) is a noninvasive method for local stimulation of cerebral cortex using a small coil's pulsed magnetic field. TMS response maps consist of measured responses to stimulations at points on a scalp-referenced grid and are used to study the topography of the brain's inhibitory and excitatory response. Because the magnetic field distributions of stimulation coils are 1-2 centimeters wide and 2-3 centimeters long, and the induced electric fields are even broader, the resolution of TMS maps is limited and the actual region of cortical stimulation is poorly defined. To better characterize the activation pattern, a practical mathematical procedure was developed for deconvolving a spherical model approximation of the coil's induced electric field distribution (here measured in a phantom) from the TMS response maps. This procedure offers an integrated, internally consistent method for processing TMS response maps to estimate the spatial distribution of motor cortex activations and inhibitions. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Bohning, DE (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. NR 43 TC 23 Z9 23 U1 0 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PY 2001 VL 108 IS 1 BP 35 EP 52 DI 10.1007/s007020170095 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 397VA UT WOS:000166717200005 PM 11261745 ER PT J AU Oliveira-Filho, J Ay, H Koroshetz, WJ Buonanno, FS AF Oliveira-Filho, J Ay, H Koroshetz, WJ Buonanno, FS TI Localization of clinical syndromes using DWI: Two examples of the "capsalar" warning syndrome SO JOURNAL OF NEUROIMAGING LA English DT Article DE MRI; brain; capsular warning syndrome ID TRANSIENT ISCHEMIC ATTACKS; MAGNETIC-RESONANCE; ACUTE STROKE; TIME-COURSE; INFARCTION; MR AB The capsular warning syndrome (CWS) is a subtype of transient ischemic attack characterized by its recurrent nature, absence of cortical signs, and high: probability of early capsular stroke. Currently, standard imaging techniques have identified only internal capsule lesions in this entity. The authors present 2 cases with an otherwise typical CWS in whom a brainstem stroke was detected by diffusion-weighted imaging (DWI). DWI's ability to differentiate between acute and chronic infarcts may assist in more accurate localization of clinical syndromes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oliveira-Filho, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Blake 1291B,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [5 RO1 NS35284, R01-NS28371, 5 P50 NS108288-22] NR 16 TC 8 Z9 8 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JAN PY 2001 VL 11 IS 1 BP 44 EP 47 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 455FR UT WOS:000170017300007 PM 11198526 ER PT J AU Yoshida, N Liberman, MC Brown, MC Sewell, WF AF Yoshida, N Liberman, MC Brown, MC Sewell, WF TI Fast, but not slow, effects of olivocochlear activation are resistant to apamin SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID OUTER HAIR-CELLS; CA2+-ACTIVATED K+ CHANNEL; GUINEA-PIG COCHLEA; POTASSIUM CHANNEL; SMALL-CONDUCTANCE; CHOLINERGIC INHIBITION; EFFERENT STIMULATION; ACETYLCHOLINE; CALCIUM; RECEPTOR AB Olivocochlear (OC) efferent suppression of auditory-nerve responses comprises a fast effect lasting tens of milliseconds and a slow effect building and decaying over tens of seconds. Both fast and slow effects are mediated by activation of the same alpha 9 nicotinic receptor. We have hypothesized that fast effects are generated at the OC synapse, but that slow effects reflect activation of calcium-activated potassium (K-Ca) channels by calcium release from the subsurface cisternae on the basolateral wall of the hair cells. We measured in vivo effects of apamin, a blocker of small-conductance (SK) K-Ca channels, and charybdotoxin, a blocker of large-conductance K-Ca channels, perfused through scala tympani, on fast and slow effects evoked by electrical stimulation of the OC bundle in anesthetized guinea pigs. Apamin selectively and reversibly reduced slow-effect amplitude without altering fast effects or baseline amplitude of the auditory-nerve response, but only when perfused at concentrations of 100 muM. In contrast, the effects of charybdotoxin were noted at 30 nM, but were not specific, reducing both afferent and efferent responses. The very high concentrations of apamin needed to block efferent effects contrasts with the high sensitivity of isolated hair cells to apamin's block of acetylcholine's effects. The results suggest that in vivo fast OC effects are dominated by a conductance that is not apamin sensitive. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Tohoku Univ, Sch Med, Dept Otolaryngol, Sendai, Miyagi 9808574, Japan. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P30 DC005209] NR 35 TC 14 Z9 14 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2001 VL 85 IS 1 BP 84 EP 88 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 390VV UT WOS:000166319300009 PM 11152708 ER PT J AU Carter, BS Brisman, JL Ogilvy, CS AF Carter, BS Brisman, JL Ogilvy, CS TI Spontaneous obliteration of an arteriovenous malformation associated with head trauma - Case illustration SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material DE arteriovenous malformation; spontaneous obliteration; traumatic brain injury C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Carter, BS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, VBK 730,32 Fruit St, Boston, MA 02114 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2001 VL 94 IS 1 BP 139 EP 139 DI 10.3171/jns.2001.94.1.0139 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 386DB UT WOS:000166043900025 PM 11147886 ER PT J AU Baliga, RR Narula, J Dec, GW AF Baliga, RR Narula, J Dec, GW TI The MIBG tarot: Is it possible to predict the efficacy of beta-blockers in congestive heart failure? SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material ID DILATED CARDIOMYOPATHY; I-123; IMPROVEMENT; CARVEDILOL; THERAPY C1 Hahnemann Univ Hosp, Philadelphia, PA 19102 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Narula, J (reprint author), Hahnemann Univ Hosp, Broad & Vine,MS115-7NT, Philadelphia, PA 19102 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JAN-FEB PY 2001 VL 8 IS 1 BP 107 EP 109 DI 10.1067/mnc.2001.112837 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 409FR UT WOS:000167374300013 PM 11303496 ER PT J AU Tawakol, A Gewirtz, H AF Tawakol, A Gewirtz, H TI Invited commentary - Does CABG improve left ventricular ejection fraction in patients with ischemic cardiomyopathy, and does it matter? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID CORONARY-ARTERY DISEASE; EMISSION COMPUTED-TOMOGRAPHY; HEART-FAILURE SYMPTOMS; MYOCARDIAL VIABILITY; DOBUTAMINE ECHOCARDIOGRAPHY; HIBERNATING MYOCARDIUM; VIABLE MYOCARDIUM; EXERCISE CAPACITY; PREDICTIVE VALUE; BYPASS-SURGERY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit Vincent Burnham 3, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit Vincent Burnham 3, Boston, MA 02114 USA. NR 29 TC 2 Z9 3 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2001 VL 42 IS 1 BP 87 EP 90 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 392TV UT WOS:000166429400036 PM 11197986 ER PT J AU Corless, IB Nicholas, PK Nokes, KM AF Corless, IB Nicholas, PK Nokes, KM TI Issues in cross-cultural quality-of-life research SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE cross-cultural; quality of life; translation ID SF-36 HEALTH SURVEY; IQOLA PROJECT; 10 COUNTRIES; INSTRUMENTS; EQUIVALENCE; CANCER; MODEL AB Purpose: To examine cross-cultural measurement of quality of life (QOL) and issues to consider in adapting quality-of-life instruments. Organizing Construct: Health-related quality of life. Methods: Review of the literature on cross-cultural QOL using the Cumulative Index to Nursing & Allied Health Literature (CINAHL), 1982 to February 2000, and Medline, 1966 to May 2000, databases. Findings: Use of research instruments beyond the samples with which they were initially tested, particularly if the new samples are cross-cultural, presents considerable challenges. The findings indicate consideration of these problems: phenomenon of interest, cross-cultural versus cross-national, salience, conceptual equivalence, cultural hegemony versus cultural validity, cultural equivalence versus verbal equivalence, fidelity versus appropriateness, privacy versus disclosure, appropriateness of format, and resource utilization for translation. Although the literature indicates increased discussion of theoretical, conceptual, and operational approaches to measuring cross-cultural QOL, problems continue in adapting instruments from one culture to another. Conclusions: Many issues about cross-cultural QOL were identified. By addressing these issues, researchers can develop appropriately translated and validated quality-of-life instruments to advance knowledge about cross-cultural QOL. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. CUNY Hunter Coll, Hunter Bellevue Sch Nursing, New York, NY 10021 USA. RP Corless, IB (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. OI Corless, Inge/0000-0003-0438-2037 NR 26 TC 40 Z9 41 U1 0 U2 1 PU SIGMA THETA TAU INT PI INDIANAPOLIS PA 550 W NORTH STREET, INDIANAPOLIS, IN 46202 USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2001 VL 33 IS 1 BP 15 EP 20 DI 10.1111/j.1547-5069.2001.00015.x PG 6 WC Nursing SC Nursing GA 435JH UT WOS:000168878000011 PM 11253575 ER PT J AU Teitelbaum, JE Walker, WA AF Teitelbaum, JE Walker, WA TI Review: the role of omega 3 fatty acids in intestinal inflammation SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Omega 3 fatty acids; fish oil; anti-inflammatory; inflammatory bowel disease ID FISH-OIL SUPPLEMENTATION; ACTIVE ULCERATIVE-COLITIS; IA-ANTIGEN EXPRESSION; SERUM-LIPID LEVELS; CROHNS-DISEASE; ARACHIDONIC-ACID; DIETARY SUPPLEMENTATION; DOCOSAHEXAENOIC ACID; LYMPHOCYTE FUNCTIONS; BOWEL-DISEASE AB The role of polyunsaturated fatty acids (PUFAs) in inflammatory lesions of the intestines is the subject of increasing research. This review begins with a background discussion of the source, elongation, and desaturation of PUFAs, as well as the role they have played in the human diet through evolution. The available data and hypotheses as to how manipulation of PUFAs might effect the various components of the immune system are then provided. Possible mechanisms by which PUFAs result in immunomodulation include alterations in eicosanoid synthesis, membrane fluidity, signal transduction, intraluminal bacteria, and gene expression. Attention is then turned to the known effects that these polyunsaturated fatty acids have on the various individual components of the immune system including lymphocytes, neutrophils, and antigen presenting cells, as well as the immunoregulatory process of apoptosis. Finally, laboratory data on the role of PUFAs in necrotizing enterocolitis, and to a greater extent inflammatory bowel disease, first as demonstrated in animal models of the disease, and second in human studies are then summarized. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Nutr, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Med Coll Penn & Hahnemann Univ, Sch Med Pediat Gastroenterol & Nutr, Monmouth Med Ctr, Long Branch, NJ USA. RP Walker, WA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Nutr, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. NR 93 TC 73 Z9 79 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JAN PY 2001 VL 12 IS 1 BP 21 EP 32 DI 10.1016/S0955-2863(00)00141-8 PG 12 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 402RY UT WOS:000167003000004 ER PT J AU Bonassar, LJ Grodzinsky, AJ Frank, EH Davila, SG Bhaktav, NR Trippel, SB AF Bonassar, LJ Grodzinsky, AJ Frank, EH Davila, SG Bhaktav, NR Trippel, SB TI The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID CONTINUOUS PASSIVE MOTION; PROTEOGLYCAN SYNTHESIS; BIOSYNTHETIC RESPONSE; HYDROSTATIC-PRESSURE; INDIVIDUAL CELLS; SYNOVIAL-FLUID; EXPLANTS; CHONDROCYTES; DEGRADATION; STIMULATION AB Articular cartilage is routinely subjected to mechanical farces and to cell-regulatory molecules, Previous studies have shown that mechanical stimuli can influence articular chondrocyte metabolic activity, and biochemical studies have shown that growth factors and cytokines control many of the same cell functions. Little is known, however, of the relationships or interplay, if any, between these two key components of the articular environment. This study investigated the comparative and interactive effects of low amplitude, sinusoidal. dynamic compression: and insulin-like growth factor-I (IGF-I) a polypeptide in synovial fluid that is anabolic for cartilage. In bovine patellofemoral cartilage explants, IGF-I increased protein and proteoglycan synthesis 90%, and 120%. respectively while dynamic compression increased protein and proteoglycan synthesis 40% and 90%, respectively. Stimulation by IC;FI was significantly greater than by dynamic compression for both protein and proteoglycan synthesis. When applied together, the two stimuli enhanced protein and proteoglycan synthesis by 180% and 290%, respectively, a degree greater than that achieved by either stimulus alone. IGF-I augmented protein synthesis with a time constant of 12.2 h. Dynamic compression increased protein synthesis with a time constant of 2.9 h, a rate significantly faster than that of IGF-I, suggesting that these signals act via distinct cell activation pathways. When used together, dynamic compression and IGF-I acted with a time constant of 5.6 h. Thus, dynamic compression accelerated the biosynthetic response to IGF-I and increased transport of IGF-I into the articular cartilage matrix, suggesting that, in addition to independently stimulating articular chondrocytes, cyclic compression may improve the access of soluble growth factors to these relatively isolated cells. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA. MIT, Dept Elect Engn & Comp Sci, Ctr Biomed Engn, Cambridge, MA 02139 USA. RP Trippel, SB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 FU NIAMS NIH HHS [AR31068, AR33236] NR 36 TC 136 Z9 147 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD JAN PY 2001 VL 19 IS 1 BP 11 EP 17 DI 10.1016/S0736-0266(00)00004-8 PG 7 WC Orthopedics SC Orthopedics GA 423MA UT WOS:000168179000002 PM 11332605 ER PT J AU Parsons, SK Levine, KJ Hoorntje, LE Eichelberger, WJ Mayer, DK Guinan, EC AF Parsons, SK Levine, KJ Hoorntje, LE Eichelberger, WJ Mayer, DK Guinan, EC TI Impact of pharmacy practices on the cost of colony-stimulating factor use in pediatric stem cell transplantation: An institution-based analysis SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE colony-stimulating factors; growth factors; transplant; stem cell; drug costs; costs and cost analysis; decision support techniques AB Purpose: An evaluation of colony-stimulating factor (CSF) use in pediatric stem cell transplantation (SCT) was conducted to identify potential cost-efficiencies while preserving institutional standards of patient care. Methods: Clinical and pharmacy records of the 55 SCTs performed during fiscal year 1995 were reviewed. Material costs per vial and per microgram, exclusive of preparation or overhead costs, were used. The best costing strategy was defined as the least expensive stocking and dispensing practice to deliver the drug actually used during the study period. Results: CSFs were used in 35 of 55 transplants; 68% of usage was protocol-mandated to enhance engraftment; the remainder was associated with life-threatening complications of SCT. All use was consistent with published evidence-based guidelines. Changes in stocking and dispensing practices would result in an overall annual savings of $48,162 (fiscal year 1995 dollars), a 39% decrease in cost without a change in clinical application. Conclusions: Our analysis demonstrates that stocking and dispensing practices place significant fiscal burden in the care of pediatric-aged patients and must be carefully considered. This analysis presents a model for evaluating all components of drug cost from a global perspective, highlighting a need for examination of pharmacy and manufacturing as well as clinical practices. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pharm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Parsons, SK (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 10 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JAN PY 2001 VL 23 IS 1 BP 19 EP 24 DI 10.1097/00043426-200101000-00006 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 391KM UT WOS:000166355200005 PM 11196264 ER PT J AU Fauza, DO Marler, JJ Koka, R Forse, RA Mayer, JE Vacanti, JP AF Fauza, DO Marler, JJ Koka, R Forse, RA Mayer, JE Vacanti, JP TI Fetal tissue engineering: Diaphragmatic replacement SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 25-29, 2000 CL ORLANDO, FLORIDA SP Amer Pediat Surg Assoc DE fetal surgery; tissue engineering; videofetoscopy; congenital diaphragmatic hernia; diaphragm; congenital anomalies; birth defects; fetus; prenatal; neonate; transplantation ID EXTRACORPOREAL MEMBRANE-OXYGENATION; AC ELECTRIC-FIELDS; HERNIA; REPAIR; ECMO; REORGANIZATION AB Background/Purpose: Prosthetic repair of congenital diaphragmatic hernia has been associated with high complication rates. This study was aimed at applying fetal tissue engineering to diaphragmatic replacement. Methods: Fetal lambs underwent harvest of skeletal muscle specimens. Once expanded in vitro, fetal myoblasts were suspended in a collagen hydrogel submitted to controlled radial tension. The construct was then placed in a bioreactor. After birth, all animals underwent creation of 2 diaphragmatic defects. One defect was repaired with the autologous-engineered construct placed in between 2 acellular supporting membranes and the other with an identical construct but without any cells. Each animal was its own control (graft, n = 10). Animals were killed at different time-points postimplantation for histologic examination. Statistical analysis was by analysis of variance (ANOVA). Results: Fetal myoblasts expanded up to twice as fast as neonatal cells. Hydrogel-based radial tension enhanced construct architecture by eliciting cell organization within the scaffold. No eventration was present in 4 of 5 engineered constructs but in 0 of 5 acellular grafts (P < .05). At harvest, engineered constructs were thick and histologically resembled normal skeletal muscle, whereas acellular grafts were thin, floppy, and showed low cell density with increased fibrosis. Conclusions: Unlike acellular grafts, engineered cellular diaphragmatic constructs are anatomically and histologically similar to normal muscle. Fetal tissue engineering may be a viable alternative for diaphragmatic replacement. J Pediatr Surg 36:146-151. Copyright (C) 2001 by W.B. Saunders Company. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Ctr Minimally Invas Surg, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 1157, Boston, MA 02114 USA. NR 21 TC 68 Z9 70 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 2001 VL 36 IS 1 BP 146 EP 151 DI 10.1053/jpsu.2001.20034 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 388KW UT WOS:000166180500026 PM 11150454 ER PT J AU Ruppel, RA Kochanek, PM Adelson, PD Rose, ME Wisniewski, SR Bell, MJ Clark, RSB Marion, DW Graham, SH AF Ruppel, RA Kochanek, PM Adelson, PD Rose, ME Wisniewski, SR Bell, MJ Clark, RSB Marion, DW Graham, SH TI Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children: The role of child abuse SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Congress of the American-Academy-of-Pediatrics CY OCT 16-19, 1998 CL SAN FRANCISCO, CA SP Amer Acad Pediat ID SHAKEN-BABY SYNDROME; NONACCIDENTAL HEAD-INJURY; CENTRAL-NERVOUS-SYSTEM; DEVELOPING RAT-BRAIN; METHYL-D-ASPARTATE; YOUNG-CHILDREN; NEUROTOXICITY; BLOCKADE; RELEASE; CSF AB Background: Excitotoxicity is an important mechanism in secondary neuronal injury after traumatic brain injury (TBI). Excitatory amino acids (EAAs) are increased in cerebrospinal fluid (CSF) in adults after TBI; however, studies in pediatric head trauma are lacking. We hypothesized that CSF glutamate, aspartate, and glycine would be increased after TBI in children and that these increases would be associated with age, child abuse, poor outcome, and cerebral ischemia. Methods: EAAs were measured in 66 CSF samples from 18 children after severe TBI. Control samples were obtained from 19 children who received lumbar punctures to rule out meningitis. Results: Peak and mean CSF glycine and peak CSF glutamate levels were increased versus control values. Subgroups of patients with TBI were compared by using univariate regression analysis. Massive increases in CSF glutamate were found in children <4 years old and in child abuse victims. Increased CSF glutamate and glycine were associated with poor outcome. A trend toward an association between high glutamate concentration and ischemic blood flow was observed. Conclusions: CSF EAAs are increased in infants and children with severe TBI. Young age and child abuse were associated with extremely high CSF glutamate concentrations after TBI. A possible role for excitotoxicity after pediatric TBI is supported. C1 Univ Pittsburgh, Sch Med,Childrens Hosp Pittsburgh, Dept Anesthesiol & Crit Care Med, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Safar Ctr Resuscitat Res,Dept Pediat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Safar Ctr Resuscitat Res,Dept Neurol Surg, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Safar Ctr Resuscitat Res,Dept Neurol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med,Childrens Hosp Pittsburgh, Dept Epidemiol & Publ Hlth, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Kochanek, PM (reprint author), Univ Pittsburgh, Sch Med,Childrens Hosp Pittsburgh, Safar Ctr Resuscitat Res, 3434 5th Ave,Suite 201, Pittsburgh, PA 15260 USA. RI Kochanek, Patrick/D-2371-2015; OI Kochanek, Patrick/0000-0002-2627-913X; Wisniewski, Stephen/0000-0002-3877-9860 NR 34 TC 60 Z9 61 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2001 VL 138 IS 1 BP 18 EP 25 DI 10.1067/mpd.2001.110979 PG 8 WC Pediatrics SC Pediatrics GA 393PK UT WOS:000166478700005 PM 11148507 ER PT J AU Hintz, SR Benaron, DA Siegel, AM Zourabian, A Stevenson, DK Boas, DA AF Hintz, SR Benaron, DA Siegel, AM Zourabian, A Stevenson, DK Boas, DA TI Bedside functional imaging of the premature infant brain during passive motor activation SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE brain; functional imaging; infant; near-infrared; neonate; optical ID CEREBRAL BLOOD-FLOW; CYSTIC PERIVENTRICULAR LEUKOMALACIA; BIRTH-WEIGHT INFANTS; COMPUTED-TOMOGRAPHY; MOVEMENT-DISORDERS; PRETERM INFANTS; CHILDREN; SPECT; OXYGENATION; ABNORMALITIES AB Background: Changes in regional brain blood flow and hemoglobin oxygen saturation occur in the human cortex in response to neural activation. Traditional functional radiologic methods cannot provide continuous, portable measurements. Imaging methods, which use near-infrared light allow for non-invasive measurements by taking advantage of the fact that hemoglobin is a strong absorber at these wavelengths. Aims: To test the feasibility of a new optical functional imaging system in premature infants, and to obtain preliminary brain imaging of passive motor activation in this population. Methods: A new optical imaging system, the Diffuse Optical Tomography System (DOTS), was used to provide real-time, bedside assessments. Custom-made soft flexible fiberoptic probes were placed on two extremely ill, mechanically ventilated 24 week premature infants, and three healthier 32 week premature infants. Passive motor stimulation protocols were used during imaging. Results: Specific movement of the arm resulted in reproducible focal, contralateral changes in cerebral absorption. The data suggest an overall increase in blood volume to the imaged area, as well as an increase in deoxyhemoglobin concentration. These findings in premature infants differ from those expected in adults. Conclusions: In the intensive care setting, continuous non-invasive optical functional imaging could be critically important and, with further study, may provide a bedside monitoring tool for prospectively identifying patients at high risk for brain injury. C1 Stanford Univ, Sch Med, Div Neonatal & Dev Med, Biomed Opt Grp, Palo Alto, CA 94304 USA. Hansen Phys Lab, Palo Alto, CA USA. Harvard Univ, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RP Hintz, SR (reprint author), Stanford Univ, Sch Med, Div Neonatal & Dev Med, Biomed Opt Grp, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. FU NINDS NIH HHS [1 N29 NS38842 AO1, N43-NS-6-2313, N43-NS-6-2314, N43-NS-6-2315]; PHS HHS [MO1-00070] NR 33 TC 86 Z9 87 U1 0 U2 3 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2001 VL 29 IS 4 BP 335 EP 343 DI 10.1515/JPM.2001.048 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 470JJ UT WOS:000170867600010 PM 11565203 ER PT J AU Bellack, JP Morjikian, R Barger, S Strachota, E Fitzmaurice, J Lee, A Kluzik, T Lynch, E Tsao, J O'Neil, EH AF Bellack, JP Morjikian, R Barger, S Strachota, E Fitzmaurice, J Lee, A Kluzik, T Lynch, E Tsao, J O'Neil, EH TI Developing BSN leaders for the future: the Fuld Leadership Initiative for Nursing Education (LINE) SO JOURNAL OF PROFESSIONAL NURSING LA English DT Article DE baccalaureate education; leadership; leadership competencies; curriculum changes; emotional intelligence AB The Helene Fuld Leadership Initiative in Nursing Education (LINE) program was designed to enhance beginning leadership competencies of baccalaureate nursing students. Given the increasing need for strong and effective leadership throughout the health care system, and the demands new graduates encounter as they move into practice, the LINE program is built on the premise that leadership skills must be instilled at the undergraduate level. The program achieves its goal through an intensive 5-day institute focused on assessing and developing the leadership competencies of nurse educators and their clinical partners to enable them to be effective agents of curriculum change in their home institutions. The institute also assists participants to redesign their baccalaureate nursing (BSN) curricula to ensure that students learn to: (1) work effectively within and across complex, integrated organizational and institutional boundaries; (2) think and act from the perspective of a system; and (3) communicate, negotiate, lead, and facilitate change within health care organizations. D. Goleman's (1998) framework of emotional intelligence, which addresses both personal competence (managing oneself) and social competence (handling one's relationships with others) provides the framework for operationalizing leadership in the BSN curriculum. To date, 26 BSN programs and their clinical partners have participated in the LINE program, which has the potential to influence the beginning leadership development of more than 2,400 BSN students. Program outcomes reveal that education-practice collaboration, professional networking, individual leadership development of nurse educators and their clinical partners as change agents, and the integration of leadership experiences at all levels of the BSN curriculum are important in developing beginning leadership competencies in BSN students. (C) 2001 by W.B. Saunders Company. C1 Massachusetts Coll Pharm & Hlth Sci, Boston, MA 02115 USA. UCSF, Ctr Hlth Profess, Training Div, San Francisco, CA USA. Univ Alabama, Capstone Coll Nursing, Tuscaloosa, AL USA. Grand View Coll, Div Nursing, Des Moines, IA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. S Carolina Dept Hlth & Environm Control, Columbia, SC USA. UCSF, Ctr Hlth Profess, Natl Fund Med Educ, San Francisco, CA USA. UCSF, Ctr Hlth Profess, LINE Program, San Francisco, CA USA. Pew Hlth Profess Commiss, San Francisco, CA USA. RP Bellack, JP (reprint author), Massachusetts Coll Pharm & Hlth Sci, 179 Longwood Ave, Boston, MA 02115 USA. NR 9 TC 18 Z9 18 U1 2 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 8755-7223 J9 J PROF NURS JI J. Prof. Nurs. PD JAN-FEB PY 2001 VL 17 IS 1 BP 23 EP 32 DI 10.1053/jpnu.2001.20247 PG 10 WC Nursing SC Nursing GA 397DF UT WOS:000166677500008 PM 11211379 ER PT J AU Powe, BD AF Powe, BD TI Cancer fatalism among elderly African American women: Predictors of the intensity of the perceptions SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE cancer fatalism; African Americans; elderly ID FECAL-OCCULT-BLOOD; COLORECTAL-CANCER; PERSPECTIVES; PREVENTION; STATISTICS AB Cancer Fatalism has been identified as a barrier to colorectal cancer screening among the rural elderly, yet cancer fatalism may not be an all-or-none phenomenon, which suggests higher levels of cancer fatalism may have a more significant influence on screening behaviors. Therefore, this descriptive study attempted to differentiate higher and lower levels of cancer fatalism and to identify predictors of high levels of fatalism among 204 elderly African American women who attended senior citizen centers in a southern state. Data were collected using the Powe Fatalism Inventory, the Knowledge of Colorectal Cancer Questionnaire. and the Demographic Data Questionnaire. The scores among women with high levels of fatalism were twice as high as the other women's scores. These women also were older, had less education, had less knowledge about colorectal cancer, and were more likely to have lower annual incomes. Age, education, and knowledge about the disease predicted high levels of fatalism. More research is needed to identify additional predictors of high levels of fatalism and to establish trends in screening behaviors when fatalistic perceptions are present. To negate the influence of these perceptions, educational strategies should target both providers and patients. C1 Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Hosp, Charleston, SC USA. RP Powe, BD (reprint author), 4204 Mill Creek Dr, N Charleston, SC 29420 USA. NR 27 TC 24 Z9 24 U1 0 U2 4 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2001 VL 19 IS 3-4 BP 85 EP 95 DI 10.1300/J077v19n03_07 PG 11 WC Psychology, Social SC Psychology GA 501KL UT WOS:000172683800007 ER PT J AU DiGiovine, CP Cooper, RA Boninger, ML AF DiGiovine, CP Cooper, RA Boninger, ML TI Dynamic calibration of a wheelchair dynamometer SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE calibration; dynamics; dynamometer; ergometer; wheelchair ID BRAKED CYCLE ERGOMETERS; PROPULSION; KINEMATICS AB The inertia and resistance of a wheelchair dynamometer must be determined in order to compare the results of one study to another, independent of the type of device used. The purpose of this study was to describe and implement a dynamic calibration test for characterizing the electro-mechanical properties of a dynamometer. The inertia, the viscous friction, the kinetic friction, the motor back-electromotive force constant, and the motor constant were calculated using three different methods. The methodology based on a dynamic calibration test along with a nonlinear regression analysis produced the best results. The coefficient of determination comparing the dynamometer model output to the measured angular velocity and torque was 0.999 for a ramp input and 0.989 for a sinusoidal input. The inertia and resistance were determined for the rollers and the wheelchair wheels. The calculation of the electro-mechanical parameters allows for the complete description of the propulsive torque produced by an individual, given only the angular velocity and acceleration. The measurement of the electro-mechanical properties of the dynamometer as well as the wheelchair/human system provides the information necessary to simulate real-world conditions. C1 VA Pittsburgh Healthcare Syst, Ctr Excellence Wheelchairs & Related Technol, Human Engn Res Labs 151R1, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Mech Engn, Pittsburgh, PA 15261 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Excellence Wheelchairs & Related Technol, Human Engn Res Labs 151R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI DiGiovine, Carmen/E-2982-2011; OI Boninger, Michael/0000-0001-6966-919X NR 33 TC 36 Z9 36 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JAN-FEB PY 2001 VL 38 IS 1 BP 41 EP 55 PG 15 WC Rehabilitation SC Rehabilitation GA 422ZJ UT WOS:000168149100009 PM 11322470 ER PT J AU Dawson, TM Starkebaum, G Wood, BL Willkens, RF Gown, AM AF Dawson, TM Starkebaum, G Wood, BL Willkens, RF Gown, AM TI Epstein-Barr virus, methotrexate, and lymphoma in patients with rheumatoid arthritis and primary Sjogren's syndrome: Case series SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE Epstein-Barr virus; rheumatoid arthritis; lymphoma; methotrexate; Sjogren's syndrome ID LOW-DOSE METHOTREXATE; NON-HODGKINS-LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS; HEMATOLOGIC MALIGNANCIES; REVERSIBLE LYMPHOMAS; LONG-TERM; CANCER; DISEASE; IMMUNOSUPPRESSION; ASSOCIATION AB Objective. Rheumatoid arthritis (RA) and primacy Sjogren's syndrome (SS) are associated with an increased risk of lymphoma. Epstein-Barr virus (EBV), a ubiquitous herpes virus, has been linked etiologically to lymphoma in patients with RA and primary SS. Recently, methotrexate (MTX) has also been linked to the development of these lymphomas. We investigated the frequency of EBV in lymphoma tissue of patients with RA and primary SS and the association of MTX with lymphomagenesis. Methods. Twenty-three patients with RA and 9 with primary SS with a history of lymphoma were identified by writing to all Arthritis Foundation member rheumatologists in Washington State. Formalin fixed, paraffin embedded tissue blocks were then requested from pathology laboratories. Lymph nodes from 5 RA patients without lymphoma were also studied. In situ hybridization using a biotinylated EBER-1 oligonucleotide probe was used to detect EBV in tissue sections. Positive and negative laboratory controls were used to ensure procedural integrity. Results. Specimens from 21 RA patients were obtained, with 2 subsequently excluded due to specimen quality, Specimens from 6 patients with primary SS were obtained. In situ hybridization for EBV was positive in 5/19 (26%) RA patients and 1/6 patients with primary SS. In the nonmalignant lymph nodes no patient showed EBV. One primary SS and 12 RA patients were known to be taking MTX at the time of lymphoma diagnosis. Of the EBV positive RA lymphoma patients, 4/5 were receiving MTX at the time of diagnosis. These results show that EBV is present in lymphoma tissue of some patients with RA and very few with primary SS. Conclusion. EBV is over-represented in the lymphomas of patients with RA, but whether MTX plays a role in predisposing patients with RA and primary SS to the development of lymphoma, perhaps by influencing behavior of EBV, remains unclear. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Arthrit Sect, Seattle, WA 98108 USA. Univ Washington, Harborview Med Ctr, Med Serv, Arthrit Sect, Seattle, WA 98104 USA. Univ Washington, Div Rheumatol, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. PheonPath Labs, Seattle, WA USA. Immunochem Res Inst, Seattle, WA USA. RP Dawson, TM (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Arthrit Sect, 1600 S Columbian Way, Seattle, WA 98108 USA. NR 58 TC 47 Z9 47 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2001 VL 28 IS 1 BP 47 EP 53 PG 7 WC Rheumatology SC Rheumatology GA 390XH UT WOS:000166324700009 PM 11196542 ER PT J AU Warner, JJP Higgins, L Parsons, IM Dowdy, P AF Warner, JJP Higgins, L Parsons, IM Dowdy, P TI Diagnosis and treatment of anterosuperior rotator cuff tears SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID SUBSCAPULARIS MUSCLE; TENDON AB Nineteen of 407 patients who underwent rotator cuff repair surgery over a 6-year period were found to have a tear of the subscapularis in combination with the supraspinatus and infraspinatus tendons. Nine of these patients had an unsuccessful prior surgery which failed to recognize the extent of the subscapularis component. Surgical repair of the subscapularis tendon required a deltopectoral approach, and repair of the supraspinatus and infraspinatus components of the tear could only be accomplished through this approach in 4 patients. In the remaining 15, an extended superior approach was required to mobilize and repair the supraspinatus and infraspinatus tendons. In all cases, the biceps tendon was either torn or severely degenerated requiring tenodesis. At a mean Follow-vp of 40 months (range 24 to 75 months), subjective results were excellent in 5 patients, good in 3, Fair in 4, and poor in 7. The modified Constant score improved to a mean of 69% (range 23% to 130%), compared with a preoperative mean of 38% (range 23% to 100%). Physical findings positive for subscapularis insufficiency persisted in 14 of 19 patients. A significant correlation (P < .05) was found between a lower Constant score and duration of symptoms longer than 6 months as well as an appearance of severe fatty degeneration and atrophy of the subscapularis muscle on magnetic resonance imaging. We conclude that anterosuperior rotator cuff tears are an infrequent configuration that may require surgical repair through an extended approach combining deltopectoral mobilization of the subscapularis with transdeltoid mobilization of the supraspinatus and infraspinatus. Repair before 6 months of symptoms is associated with a better functional outcome and is the result of less involution of muscle and tendon tissue. C1 Harvard Univ, Massachusetts Gen Hosp, Partners Dept Orthopaed Surg, Shoulder Serv, Boston, MA 02114 USA. Duke Univ, Med Ctr, Div Orthopaed Surg, Sports Med Serv, Durham, NC 27710 USA. Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Pittsburgh, PA 15260 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Partners Dept Orthopaed Surg, Shoulder Serv, Profess Off Bldg,Suite 403,275 Cambridge St, Boston, MA 02114 USA. NR 52 TC 133 Z9 136 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JAN-FEB PY 2001 VL 10 IS 1 BP 37 EP 46 DI 10.1067/mse.2001.112022 PG 10 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 404XV UT WOS:000167128400007 PM 11182734 ER PT J AU Hanna, EZ Yi, HY Dufour, MC Whitmore, CC AF Hanna, EZ Yi, HY Dufour, MC Whitmore, CC TI The relationship of early-onset regular smoking to alcohol use, depression, illicit drug use, and other risky behaviors during early adolescence: Results from the youth supplement to the Third National Health and Nutrition Examination Survey SO JOURNAL OF SUBSTANCE ABUSE LA English DT Article DE smoking; drinking; drug use; pregnancy; adolescence ID SUBSTANCE USE; PSYCHIATRIC-DISORDERS; EPIDEMIOLOGIC SURVEY; MAJOR DEPRESSION; UNITED-STATES; COMORBIDITY; DEPENDENCE; PREDICTORS; NICOTINE; GENDER AB Purpose: Recently we found that the early onset of regular tobacco use is as predictive of lifetime drug use and depressive disorders as it is of alcohol use disorders [Alcohol.: Clin. Exp. Res. 23 (1999) 513.]. This finding, which paralleled findings regarding early onset of alcohol use [J. Subst. Abuse 10 (1998) 59.], suggested that early regular use of any drug might simply be an indicator of risk for a constellation of problem behaviors. The purpose of the present study is to test this hypothesis as well as to study the strength and patterns of associations among these problem behaviors already present among youth. The results will permit description of more precise profiles to identify groups of children at risk. Methods: Using data for respondents aged 12-16 from the Third National Health and Nutrition Examination Survey (NHANES III), descriptive statistics were calculated and logistic regression models were estimated. Results: Descriptive analyses indicated that in comparison with those who never smoked, or who simply experimented, early-onset regular smokers, both those who began at age 13 or younger and those who did so between 14 and 16, were those most likely to use alcohol and other drugs as well as have school problems and early sexual experiences culminating in pregnancy. Multivariate logistic regression analyses were conducted to assess the associations among these high-risk behaviors. Implications: These results support the hypothesis that early onset of smoking is but an indicator of a syndrome of problem behaviors already in place during childhood. They also suggest that the significance of an age onset variable may differ depending on the age of the sample used. As follow-up data are collected, we expect to learn much about the natural course of the distinct risk groups identified in the analyses by studying longitudinally this nationally representative group of early adolescents. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIAAA, Div Biometry & Epidemiol, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. CSR Inc, Alcohol Epidemiol Data Syst, Washington, DC USA. RP Hanna, EZ (reprint author), NIAAA, Div Biometry & Epidemiol, 6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 33 TC 66 Z9 67 U1 6 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-3289 J9 J SUBST ABUSE JI J. SUBST. ABUSE PY 2001 VL 13 IS 3 BP 265 EP 282 DI 10.1016/S0899-3289(01)00077-3 PG 18 WC Substance Abuse SC Substance Abuse GA 485UB UT WOS:000171781500003 PM 11693451 ER PT J AU Biswas, KS Thatte, HS Najjar, SF Rhee, JH Birjiniuk, V Crittenden, MD Michel, T Khuri, SF AF Biswas, KS Thatte, HS Najjar, SF Rhee, JH Birjiniuk, V Crittenden, MD Michel, T Khuri, SF TI Multi-photon microscopy in the evaluation of human saphenous vein SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE multi-photon microscopy; saphenous vein; endothelial cell; viability; nitric oxide; diaminofluorescein; calcein; ethidium homodimer ID NITRIC-OXIDE; FLUORESCENCE MICROSCOPY; PRESERVATION; GRAFTS; DIAMINOFLUORESCEINS; ENDOTHELIUM; INDICATORS; DAMAGE; INJURY AB Background. The use of conventional fluorescence microscopy to image biological systems at the cellular level is limited by its inability to spatially resolve thick tissues. We have applied the technique of multiphoton fluorescence microscopy to study the structure and function of endothelial cells in living human saphenous vein taken from patients undergoing coronary artery bypass surgery. Materials and Methods. Vein segments were preserved for 1-4 h to determine the temporal effects of storage. The effect of pH on endothelial and smooth muscle cell viability was examined by storing segments at pH 6.0, 7.4, and 8.0. Calcein-mediated green fluorescence and ethidium homodimer-mediated red fluorescence were used to differentiate cell viability. Increases in diaminofluorescein fluorescence were used to measure bradykinin activation of endothelial nitric oxide synthase (eNOS) with or without N-nitro-L-arginine (L-NNA). Multi-photon imaging was performed with the BioRad MRC1024ES system. Results. Successful imaging of endothelial and smooth muscle cells of vein segments was achieved. Cell viability was well preserved up to 3 h of storage but dramatically decreased after 4 h, Cell viability was maintained at pH 7.4, diminished at pH 8.0, and was completely lost at pH 6.0. A two- to threefold increase in eNOS activity was observed upon activation by bradykinin which was completely inhibited in L-NNA-treated samples. Conclusions. We have demonstrated the successful application of multi-photon microscopy in imaging and quantifying nitric oxide production and cell viability under various storage conditions in human saphenous veins, This imaging technique allows for the functional imaging of cellular processes and may have diagnostic potential in cardiovascular surgery for patients undergoing bypass operations. (C) 2001 Academic Press. C1 Brigham & Womens Hosp, VA Boston Healthcare Syst, Div Cardiothorac Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, VA Boston Healthcare Syst, Div Multiphoton Imaging Core, Boston, MA 02115 USA. Brigham & Womens Hosp, VA Boston Healthcare Syst, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 25 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2001 VL 95 IS 1 BP 37 EP 43 DI 10.1006/jsre.2000.6019 PG 7 WC Surgery SC Surgery GA 391KN UT WOS:000166355300007 PM 11120633 ER PT J AU Ravicz, ME Melcher, JR AF Ravicz, ME Melcher, JR TI Isolating the auditory system from acoustic noise during functional magnetic resonance imaging: Examination of noise conduction through the ear canal, head, and body SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article; Proceedings Paper CT 4th International Conference on Functional Mapping of the Human Brain CY JUN 07-12, 1998 CL MONTREAL, CANADA ID HEARING PROTECTION DEVICES; STANDARD LABORATORY PROTOCOL; FIELD ATTENUATION; CORTEX; FMRI AB Approaches were examined for reducing acoustic noise levels heard by subjects during functional magnetic resonance imaging (fMRI), a technique for localizing brain activation in humans. Specifically, it was examined whether a device for isolating the head and ear canal from sound (a "helmet") could add to the isolation provided by conventional hearing protection devices (i.e., earmuffs and earplugs). Both subjective attenuation (the difference in hearing threshold with versus without isolation devices in place) and objective attenuation (difference in ear-canal sound pressure) were measured. In the frequency range of the most intense fMRI noise (1-1.4 kHz), a helmet, earmuffs, and earplugs used together attenuated perceived sound by 55-63 dB, whereas the attenuation provided by the conventional devices alone was substantially less: 30-37 dB for earmuffs, 25-28 dB for earplugs, and 39-41 dB for earmuffs and earplugs used together. The data enabled the clarification of the relative importance of ear canal, head, and body conduction routes to the cochlea under different conditions: At low frequencies (less than or equal to 500 Hz), the ear canal was the dominant route of sound conduction to the cochlea for all of the device combinations considered. At higher frequencies (>500 Hz), the ear canal was the dominant route when either earmuffs or earplugs were worn. However, the dominant route of sound conduction was through the head when both earmuffs and earplugs were worn, through both ear canal and body when a helmet and earmuffs were worn, and through the body when a helmet, earmuffs, and earplugs were worn. It is estimated that a helmet, earmuffs, and earplugs together will reduce the most intense fMRI noise levels experienced by a subject to 60-65 dB SPL. Even greater reductions in noise should be achievable by isolating the body from the surrounding noise field. (C) 2001 Acoustical Society of America. [DOI: 10.1121/1.1326083]. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P01 DC000119, P01 DC000119-260023, P01 DC00119] NR 52 TC 58 Z9 58 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JAN PY 2001 VL 109 IS 1 BP 216 EP 231 DI 10.1121/1.1326083 PG 16 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 391VR UT WOS:000166377400023 PM 11206150 ER PT J AU Campen, R Mankin, H Louis, DN Hirano, M MacCollin, M AF Campen, R Mankin, H Louis, DN Hirano, M MacCollin, M TI Familial occurrence of adiposis dolorosa SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MULTIPLE SYMMETRICAL LIPOMATOSIS; 10-YEAR FOLLOW-UP; DERCUMS-DISEASE; MITOCHONDRIAL-DNA; MUTATION; PAIN; LIDOCAINE; RELIEF; MTDNA; GENE AB Adiposis dolorosa is a rare condition characterized by multiple painful lipomas. We describe two typically affected siblings who were found to have at least 5 affected first-degree relatives in two generations. Manifestations were remarkable variable, ranging from complete disability to solitary asymptomatic tumors. Review of histopathologic findings did not reveal any features that might distinguish the tumors from common sporadic lipomas. Mutational analysis excluded the 8344 A to G mitochondrial mutation seen in other patients with multiple lipomas. Adiposis dolorosa may be an extreme manifestation of the more common condition of familial multiple lipomas. Further work is needed to define the genetic basis of these conditions. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol & Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Columbia Presbyterian Med Ctr, Dept Neurol, New York, NY 10032 USA. RP MacCollin, M (reprint author), Massachusetts Gen Hosp E, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01NS35878-02] NR 29 TC 18 Z9 19 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2001 VL 44 IS 1 BP 132 EP 136 DI 10.1067/mjd.2001.110872 PG 5 WC Dermatology SC Dermatology GA 389YX UT WOS:000166267200025 PM 11148491 ER PT J AU Drake, L Prendergast, M Maher, R Breneman, D Korman, N Satoi, Y Beusterien, KM Lawrence, I AF Drake, L Prendergast, M Maher, R Breneman, D Korman, N Satoi, Y Beusterien, KM Lawrence, I TI The impact of tacrolimus ointment on health-related quality of life of adult and pediatric patients with atopic dermatitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID OF-LIFE; SKIN DISEASES; CYCLOSPORINE; CARE AB Background: Atopic dermatitis can have detrimental effects on health-related quality of life (QOL). Objective: Our purpose was to examine the QOL impact of tacrolimus ointment in patients with atopic dermatitis. Methods: The Dermatology Life Quality Index (DLQI), Children's DLQI (CDLQI), and Toddler QOL Survey were used to assess QOL in adults (16 years or older), children (5-15 years), and toddlers (2-4 years) enrolled in 12-week, randomized, double-blind studies comparing two concentrations of tacrolimus ointment (0.03% and 0.1%) versus vehicle ointment for treatment of atopic dermatitis. QOL was assessed at baseline, week 3, and week 12/early discontinuation. Results: Of the 985 patients enrolled, 91.5% had evaluable QOL data. Among adults, both tacrolimus ointment groups experienced improved QOL relative to the vehicle control group for all QOL scales (P < .001). Among children and toddlers, both tacrolimus ointment groups demonstrated significant QOL improvements relative to the vehicle control group (P < .05) for all but the Personal Relationships scale in the 0.03% tacrolimus ointment group among children. Conclusion: Tacrolimus ointment is associated with significant QOL benefits in adults, children, and toddlers with atopic dermatitis. C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Fujisawa Healthcare Inc, Deerfield, IL USA. Univ Cincinnati, Coll Med, Cleveland, OH USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Covance Hlth Econ & Outcomes Serv, Washington, DC USA. RP Drake, L (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 40 Blossom St,BAR604, Boston, MA 02114 USA. NR 18 TC 50 Z9 57 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2001 VL 44 IS 1 BP S65 EP S72 DI 10.1067/mjd.2001.109814 PG 8 WC Dermatology SC Dermatology GA 390JE UT WOS:000166291300008 PM 11145797 ER PT J AU Hanifin, JM Ling, MR Langley, R Breneman, D Rafal, E AF Hanifin, JM Ling, MR Langley, R Breneman, D Rafal, E CA Tacrolimus Ointment Study Grp TI Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: Part I, Efficacy SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID FK506 OINTMENT; CYCLOSPORINE-A; TRIAL; CHILDREN; SKIN AB A total of 632 adults with atopic dermatitis applied tacrolimus ointment (0.03% or 0.1%) or vehicle twice daily for up to 12 weeks in two randomized, double-blind studies. This report focuses on the efficacy of tacrolimus ointment in these studies. The mean percent body surface area (%BSA) affected at baseline was 45%, and 56% of patients had severe atopic dermatitis. Evaluations included a physician's global evaluation of clinical response, %BSA affected, individual signs of atopic dermatitis, the Eczema Area and Severity Index (EASI) score, and the patient's assessment of pruritus. A 90% or greater improvement from baseline in disease status was observed for 6.6%, 27.5%, and 36.8% of patients in the vehicle, 0.03% tacrolimus ointment, and 0.1% tacrolimus ointment groups, respectively (P < .001), and 50% or better improvement was observed for 19.8%, 61.6%, and 72.7% of patients, respectively. Tacrolimus ointment-treated patients showed significantly greater improvement than vehicle-treated patients for all efficacy parameters evaluated, including the %BSA affected, the total score and individual scores for signs of atopic dermatitis, the patient's assessment of pruritus, and EASI score. The 0.1% concentration was more effective than the 0.03% concentration, particularly in patients with severe disease and/or extensive BSA involvement at baseline and in African Americans. Tacrolimus ointment is an effective therapy for the treatment of adult patients with atopic dermatitis on all skin regions including the head and neck. C1 Oregon Hlth Sci Univ, Dept Dermatol, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Dermatol Consultants Inc, Cincinnati, OH USA. SUNY Stony Brook, Med Ctr, Stony Brook, NY USA. RP Hanifin, JM (reprint author), Oregon Hlth Sci Univ, Dept Dermatol, Mail Code L468,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. NR 27 TC 127 Z9 138 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2001 VL 44 IS 1 BP S28 EP S38 DI 10.1067/mjd.2001.109810 PG 11 WC Dermatology SC Dermatology GA 390JE UT WOS:000166291300004 PM 11145793 ER PT J AU Rodriguez, A Bernardi, V Navia, J Baldi, J Grinfeld, L Martinez, J Vogel, D Grinfeld, R Delacasa, A Garrido, M Oliveri, R Mele, E Palacios, I O'Neill, W AF Rodriguez, A Bernardi, V Navia, J Baldi, J Grinfeld, L Martinez, J Vogel, D Grinfeld, R Delacasa, A Garrido, M Oliveri, R Mele, E Palacios, I O'Neill, W CA ERACI II Investigators TI Argentine randomized study: Coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple-vessel disease (ERACI II): 30-day and one-year follow-up results SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; BALLOON ANGIOPLASTY; GRAFT-SURGERY; ARTERY DISEASE; OUTCOMES; TRIAL; REVASCULARIZATION; IDENTIFICATION; GUIDELINES; PLACEMENT AB OBJECTIVES The purpose of this study was to compare percutaneous transluminal coronary revascularization (PTCR) employing stent implantation to conventional coronary artery bypass graft surgery (CABG) in symptomatic patients with multivessel coronary artery disease. BACKGROUND Previous randomized studies comparing balloon angioplasty versus CABG have demonstrated equivalent safety results. However, CABG was associated with significantly fewer repeat revascularization procedures. METHODS A total of 2759 patients with coronary artery disease were screened at seven clinical sites, and 450 patients were randomly assigned to undergo either PTCR (225 patients) or CABG (225 patients). Only patients with multivessel disease and indication for revascularization were enrolled. RESULTS Both groups had similar clinical demographics: unstable angina in 92%; 38% were older than 65 years, and 23% had a history of peripheral vascular disease. During the first 30 days, PTCR patients had lower major adverse events (death, myocardial infarction, repeat revascularization procedures and stroke) compared with CABG patients (3.6% vs. 12.3%, p = 0.002). Death occurred in 0.9% of PTCR patients versus 5.7% in CABG patients, p < 0.013, and Q myocardial infarction (MI) occurred in 0.9% PTCR versus 5.79/0 of CABG patients, p < 0.013. At follow-up (mean 18.5 +/- 6.4 months), survival was 96.9% in PTCR versus 92.5% in CABG, p < 0.017. Freedom from MI was also better in PTCR compared to CABG patients (97.7% vs. 93.4%, p < 0.017). Requirements for new revascularization procedures were higher in PTCR than in CABG patients (16.8% vs. 4.8%, p < 0.002). CONCLUSIONS In this selected high-risk group of patients with multivessel disease, PTCR with stent implantation showed better survival and freedom from MI than did conventional surgery. Repeat revascularization procedures were higher in the PTCR group. (J Am Cell Cardiol 2001;37:51-8) (C) 2001 by the American College of Cardiology. C1 William Beaumont Hosp, Div Cardiol, Royal Oak, MI 48073 USA. Otamendi Hosp, Buenos Aires, DF, Argentina. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP O'Neill, W (reprint author), William Beaumont Hosp, Div Cardiol, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. NR 36 TC 205 Z9 226 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN PY 2001 VL 37 IS 1 BP 51 EP 58 DI 10.1016/S0735-1097(00)01052-4 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 389KY UT WOS:000166238100008 PM 11153772 ER PT J AU Dubey, AK Chueh, HC AF Dubey, AK Chueh, HC TI Using XML metadata to enable the automatic generation and processing of HTML FORMS from XML documents SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2001 SU S BP 894 EP 894 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 494CZ UT WOS:000172263400254 ER PT J AU Murphy, SN Chueh, HC AF Murphy, SN Chueh, HC TI Visual query tool for integrating clinical and genetic data in the Partners Healthcare System SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Comp Sci Lab, Partners Healthcare Inc, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2001 SU S BP 983 EP 983 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 494CZ UT WOS:000172263400343 ER PT J AU Prady, SL Waruingi, W Norris, D Lester, JE Hoch, DB AF Prady, SL Waruingi, W Norris, D Lester, JE Hoch, DB TI User feedback in the development of an on-line communication tool for patients and providers SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2001 SU S BP 1002 EP 1002 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 494CZ UT WOS:000172263400362 ER PT J AU Zhang, Y Tsien, CL AF Zhang, Y Tsien, CL TI Prospective trials of intelligent alarm algorithms for patient monitoring SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 MIT, Comp Sci Lab, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2001 SU S BP 1068 EP 1068 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 494CZ UT WOS:000172263400428 ER PT J AU Sze, CI Bi, H Kleinschmidt-DeMasters, BK Filley, CM Martin, LJ AF Sze, CI Bi, H Kleinschmidt-DeMasters, BK Filley, CM Martin, LJ TI N-Methyl-D-aspartate receptor subunit proteins and their phosphorylation status are altered selectively in Alzheimer's disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE glutamate; excitotoxicity; hippocampus; entorhinal cortex; long-term potentiation ID LONG-TERM POTENTIATION; TYROSINE PHOSPHORYLATION; NMDA RECEPTORS; NERVOUS-SYSTEM; L-GLUTAMATE; MEMORY; HIPPOCAMPUS; MODEL; NEUROTOXICITY; IMPAIRMENT AB The N-methyl-D-aspartate (NMDA) receptor is a subtype of the ionotropic glutamate receptor that plays a pivotal role in synaptic mechanisms of learning and memory. We tested the hypothesis that NMDA receptor protein levels are abnormal in Alzheimer's disease (AD). By immunoblotting we assessed levels of both non-phosphorylated and phosphorylated receptor subunit proteins from four separate regions of 16 post-mortem brains. Three patient groups with thorough pre-mortem neuropsychological testing were evaluated, including AD, early AD (p-AD), and control patients. Protein levels and phosphorylation status of NMDA receptor subunits NR1, NR2A and NR2B were correlated with measurements of cognitive performance. Selective regional reductions in NMDA receptor subunit protein levels were found in AD compared to controls, but protein levels in the p-AD group were similar to controls. Reductions of NR1 (53%, P < 0.05) and NR2B (40%, P < 0.05) were identified in hippocampus. Reductions of NR2A (39%, P < 0.05) and NR2B (31%, P < 0.01) were found in entorhinal cortex. No reductions were noted in occipital cortex and caudate. Phosphorylated NR2A (30%, P < 0.05) and NR2B (56%, P < 0.01) were selectively reduced in entorhinal cortex in AD when compared to controls. Both phosphorylated and non-phosphorylated NMDA receptor protein levels in entorhinal cortex correlated with Mini-Mental Status Examination (MMSE) and Blessed (BIMC) scores. The losses of phosphorylated and non-phosphorylated NMDA receptor subunit proteins correlated with changes in synaptobrevin levels (a presynaptic protein), but not with age or post-mortem interval. Our results demonstrate that NMDA receptor subunits are selectively and differentially reduced in areas of AD brain, and these abnormalities correlate with presynaptic alterations and cognitive deficits in AD. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. JHUSM, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. RP Sze, CI (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pathol, B216,4200 E 9th Ave, Denver, CO 80262 USA. EM chun-i.sze@uchsc.edu FU NIA NIH HHS [AG16282] NR 39 TC 78 Z9 84 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JAN 1 PY 2001 VL 182 IS 2 BP 151 EP 159 DI 10.1016/S0022-510X(00)00467-6 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 394YQ UT WOS:000166552300011 PM 11137521 ER PT J AU Lipsitz, SR Williamson, J Klar, N Ibrahim, J Parzen, M AF Lipsitz, SR Williamson, J Klar, N Ibrahim, J Parzen, M TI A simple method for estimating a regression model for kappa between a pair of raters SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Article DE generalized estimating equations; generalized linear model; measure of agreement ID MAXIMUM-LIKELIHOOD-ESTIMATION AB Agreement studies commonly occur in medical research, for example, in the review of Xrays by radiologists, blood tests by a panel of pathologists and the evaluation of psychopathology by a panel of raters. In these studies, often two observers rate the same subject for some characteristic with a discrete number of levels. The kappa -coefficient is a popular measure of agreement between the two raters. The kappa -coefficient may depend on covariates, i.e. characteristics of the raters and/or the subjects being rated. Our research was motivated by two agreement problems. The first is a study of agreement between a pastor and a co-ordinator of Christian education on whether they feel that the congregation puts enough emphasis on encouraging members to work for social justice (yes versus no). We wish to model the kappa -coefficient as a function of covariates such as political orientation (liberal versus conservative) of the pastor and co-ordinator. The second example is a spousal education study, in which we wish to model the kappa -coefficient as a function of covariates such as the highest degree of the father of the wife and the father of the husband. We propose a simple method to estimate the regression model for the kappa -coefficient, which consists of two logistic (or multinomial logistic) regressions and one linear regression for binary data. The estimates can be easily obtained in any generalized linear model software program. C1 Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Ctr Dis Control, Atlanta, GA 30333 USA. Canc Care Ontario, Toronto, ON, Canada. Harvard Sch Publ Hlth, Boston, MA USA. Dana Farber Canc Inst, Boston, MA USA. Univ Chicago, Chicago, IL 60637 USA. RP Lipsitz, SR (reprint author), Med Univ S Carolina, Dept Biometry & Epidemiol, Suite 1148,135 Rutledge Ave,POB 250551, Charleston, SC 29425 USA. NR 14 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0964-1998 J9 J ROY STAT SOC A STA JI J. R. Stat. Soc. Ser. A-Stat. Soc. PY 2001 VL 164 BP 449 EP 465 DI 10.1111/1467-985X.00213 PN 3 PG 17 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 484MJ UT WOS:000171693900003 ER PT J AU Parise, H Wand, MP Ruppert, D Ryan, L AF Parise, H Wand, MP Ruppert, D Ryan, L TI Incorporation of historical controls using semiparametric mixed models SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE body weight; carcinogenicity; penalized spline; phenolphthalein; rodent bioassay ID TUMOR-INCIDENCE; TREND TESTS; BODY-WEIGHT; SMOOTHING SPLINES; CARCINOGENICITY; REGRESSION; PROPORTIONS; MICE AB The analysis of animal carcinogenicity data is complicated by various statistical issues. A topic of recent debate is how to control for the effect of the animals' body weight on the outcome of interest, the onset of tumours. We propose a method which incorporates historical information from the control animals in previously conducted experiments. We allow non-linearity in the effects of body weight by modelling the relationship nonparametrically through a penalized spline. A simple extension of the penalized spline model allows the relationship between weight and onset of the tumour to vary from one experiment to another. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. Cornell Univ, Ithaca, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Parise, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Sci & Engn Program, 655 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009; Ruppert, David/B-1301-2013; OI Ryan, Louise/0000-0001-5957-2490; Ruppert, David/0000-0002-6713-2257; Wand, Matt /0000-0003-2555-896X NR 29 TC 21 Z9 21 U1 0 U2 3 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2001 VL 50 BP 31 EP 42 DI 10.1111/1467-9876.00218 PN 1 PG 12 WC Statistics & Probability SC Mathematics GA 401PW UT WOS:000166938100003 ER PT J AU Parise, H Dinse, GE Ryan, LM AF Parise, H Dinse, GE Ryan, LM TI Flexible estimates of tumour incidence for intermediately lethal tumours in a typical long-term animal bioassay SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE carcinogenicity experiments; local polynomial; tumour prevalence ID SURVIVAL SACRIFICE EXPERIMENTS; CARCINOGENESIS EXPERIMENTS; TUMORIGENICITY DATA; TESTS; REGRESSION; MORTALITY; ONSET AB The estimation of the incidence of tumours in an animal carcinogenicity study is complicated by the occult nature of the tumours involved (i.e. tumours are not observable before an animal's death). Also, the lethality of tumours is generally unknown, making the tumour incidence function non-identifiable without interim sacrifices, cause-of-death data or modelling assumptions. Although Kaplan-Meier curves for overall survival are typically displayed, obtaining analogous plots for tumour incidence generally requires fairly elaborate model fitting. We present a case-study of tetrafluoroethylene to illustrate a simple method for estimating the incidence of tumours as a function of more easily estimable components. One of the components, tumour prevalence, is modelled by using a generalized additive model, which leads to estimates that are more flexible than those derived under the usual parametric models. A multiplicative assumption for tumour lethality allows for the incorporation of concomitant information, such as the size of tumours. Our approach requires only terminal sacrifice data although additional sacrifice data are easily accommodated. Simulations are used to illustrate the estimator proposed and to evaluate its properties. The method also yields a simple summary measure of tumour lethality, which can be helpful in interpreting the results of a study. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Parise, H (reprint author), Boston Univ, Dept Math & Stat, Stat & Consulting Unit, 111 Cummington St, Boston, MA 02215 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 27 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2001 VL 50 BP 171 EP 185 DI 10.1111/1467-9876.00227 PN 2 PG 15 WC Statistics & Probability SC Mathematics GA 430AR UT WOS:000168551800004 ER PT J AU Ibrahim, JG Lipsitz, SR Horton, N AF Ibrahim, JG Lipsitz, SR Horton, N TI Using auxiliary data for parameter estimation with non-ignorably missing outcomes SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE auxiliary data; EM algorithm; generalized linear models; non-ignorable missing data ID EM ALGORITHM; CHILD PSYCHOPATHOLOGY; INCOMPLETE DATA; DATA MECHANISM; MENTAL-HEALTH; MODELS; REGRESSION; NONRESPONSE; VARIABLES AB We propose a method for estimating parameters in generalized linear models when the outcome variable is missing for some subjects and the missing data mechanism is non-ignorable. We assume throughout that the covariates are fully observed. One possible method for estimating the parameters is maximum likelihood with a non-ignorable missing data model. However, caution must be used when fitting non-ignorable missing data models because certain parameters may be inestimable for some models. Instead of fitting a non-ignorable model, we propose the use of auxiliary information in a likelihood approach to reduce the bias, without having to specify a non-ignorable model. The method is applied to a mental health study. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Boston Univ, Boston, MA 02215 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. RI Horton, Nicholas/A-2493-2008; OI Horton, Nicholas/0000-0003-3332-4311 NR 21 TC 29 Z9 29 U1 0 U2 5 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2001 VL 50 BP 361 EP 373 DI 10.1111/1467-9876.00240 PN 3 PG 13 WC Statistics & Probability SC Mathematics GA 457BU UT WOS:000170117900009 ER PT J AU Leong, T Lipsitz, SR Ibrahim, JG AF Leong, T Lipsitz, SR Ibrahim, JG TI Incomplete covariates in the Cox model with applications to biological marker data SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE EM algorithm; Monte Carlo methods; non-ignorably missing data ID REGRESSION-MODELS; MULTIPLE-MYELOMA; MISSING DATA; MORPHOLOGY AB A common occurrence in clinical trials with a survival end point is missing covariate data. With ignorably missing covariate data, Lipsitz and Ibrahim proposed a set of estimating equations to estimate the parameters of Cox's proportional hazards model. They proposed to obtain parameter estimates via a Monte Carlo EM algorithm. We extend those results to non-ignorably missing covariate data. We present a clinical trials example with three partially observed laboratory markers which are used as covariates to predict survival. C1 Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Leong, T (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. NR 19 TC 5 Z9 5 U1 0 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2001 VL 50 BP 467 EP 484 DI 10.1111/1467-9876.00248 PN 4 PG 18 WC Statistics & Probability SC Mathematics GA 489GE UT WOS:000171983000005 ER PT J AU Lipsitz, SR Leong, T Ibrahim, J Lipshultz, S AF Lipsitz, SR Leong, T Ibrahim, J Lipshultz, S TI A partial correlation coefficient and coefficient of determination for multivariate normal repeated measures data SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES D-THE STATISTICIAN LA English DT Article DE clustered data; coefficient of determination; likelihood ratio statistic; longitudinal data; Wald statistic AB In a regression setting, the partial correlation coefficient is often used as a measure of 'standardized' partial association between the outcome y and each of the covariates in x' = (x(1),,..., X-K) In a linear regression model estimated by using ordinary least squares, with y as the response, the estimated partial correlation coefficient between y and x(k) can be shown to be a monotone function of the z-statistic for testing whether the regression coefficient of x(k) is 0; it can also be shown to be a monotone function of the likelihood ratio statistic. When y is normal but the data are clustered so that y and x are obtained from each member of a cluster, maximum likelihood using a multivariate normal distribution is often used to estimate the regression parameters of the model for y given x. For clustered data, we propose two measures of partial association: the exact same monotone function of the repeated measures' z-statistic that is used to form the partial correlation coefficient in the normal linear regression setting and the exact same monotone function of the likelihood ratio statistic that is used to form the partial correlation coefficient in the normal linear regression setting. We also propose an R-2-like measure which can be used to measure the overall predictive ability of the model. To illustrate the method, we use a longitudinal study concerning the stress on the wall of the heart from chemotherapy in children with leukaemia. C1 Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. RP Lipsitz, SR (reprint author), Med Univ S Carolina, Dept Biometry & Epidemiol, 135 Rutledge Ave,Suite 1148,POB 250551, Charleston, SC 29425 USA. NR 10 TC 21 Z9 21 U1 0 U2 7 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0039-0526 J9 J ROY STAT SOC D-STA JI J. R. Stat. Soc. Ser. D-Stat. PY 2001 VL 50 BP 87 EP 95 DI 10.1111/1467-9884.00263 PN 1 PG 9 WC Statistics & Probability SC Mathematics GA 413PD UT WOS:000167620200008 ER PT J AU Taylor, AE AF Taylor, AE TI Systemic adversities of ovarian failure SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article; Proceedings Paper CT Workshop on the Ovary - Genesis, Function, and Failure CY MAR 30-31, 2000 CL BETHESDA, MARYLAND SP NICHHD, Natl Inst Aging, NCI, Natl Inst Environm Hlth Sci, NIH, Off Rare Dis, NIH, Off Res Womens Hlth DE premature ovarian failure; ovary; estrogen; inhibin; follicles ID WOMEN AB Normal human ovarian function is a complex process. Ovarian failure can lead to lack of not only female estrogenic steroids, but also progestins, androgens, protein hormones and growth factors, and oocytes themselves. In addition, the process is not abrupt or immediate but often intermittent, leading to difficulties in diagnosis and treatment. The systemic impact of ovarian failure depends on the timing of ovarian failure (before or after puberty, family building, and age-expected menopause) as well as on the specific compartments that are compromised. Although the impact of reduced estrogen secretion is generally known, the systemic effects of the losses of pregnancy, progestins, androgens, and other ovarian products remain poorly understood. Finally, the underlying diseases causing premature ovarian failure may result in additional systemic symptoms. In summary, cessation of ovarian function has many physiologic implications for women that extend far beyond the loss of estrogen secretion. (J Soc Gynecol Investig 2001;8:S7-S9) Copyright (C) 2001 by the Society for Gynecologic Investigation. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Taylor, AE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5,55 Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [U54 HD-29164] NR 7 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD JAN-FEB PY 2001 VL 8 IS 1 SU S BP S7 EP S9 DI 10.1016/S1071-5576(00)00096-4 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 408ZK UT WOS:000167356900003 PM 11223361 ER PT J AU Breathnach, OS Kwiatkowski, DJ Finkelstein, DM Godleski, J Sugarbaker, DJ Johnson, BE Mentzer, S AF Breathnach, OS Kwiatkowski, DJ Finkelstein, DM Godleski, J Sugarbaker, DJ Johnson, BE Mentzer, S TI Bronchioloalveolar carcinoma of the lung: Recurrences and survival in patients with stage I disease SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID ALVEOLAR CELL-CARCINOMA; BRONCHOALVEOLAR CARCINOMA; RETROSPECTIVE ANALYSIS; SURGICAL-TREATMENT; CANCER; ADENOCARCINOMA; REAPPRAISAL; FEATURES AB Objectives: The aim of our study was to retrospectively compare the patient characteristics, the frequency and pattern of recurrent disease, and survival in patients with stage I bronchioloalveolar carcinoma and adenocarcinoma of the lung. Methods: Patients with stage I bronchioloalveolar carcinoma or adenocarcinoma other than bronchioloalveolar carcinoma resected between 1984 and 1992 with adequate clinical follow-up were studied. The clinical characteristics of the patients, extent of initial surgical resection, sites of recurrent disease, and overall survival were examined and compared between the 2 groups. The median follow-up for patients with bronchioloalveolar carcinoma and adenocarcinoma was 6.2 years and 5.9 years, respectively. Results: A total of 138 patients were identified. Thirty-three patients had bronchioloalveolar carcinoma and 105 patients had adenocarcinoma. Eleven (33%) of the patients with bronchioloalveolar carcinoma had never smoked cigarettes versus 9 (9%) of the patients with adenocarcinoma (P = .0036). There were no significant differences between patients with bronchioloalveolar carcinoma and adenocarcinoma in sex distribution and overall recurrence rate. Of the 12 patients with recurrent bronchioloalveolar carcinoma, 1 patient (8%) had extrathoracic disease develop at the site of first recurrence compared with 49% of patients with recurrent adenocarcinoma (P < .001). The 5-year survival in patients with bronchioloalveolar carcinoma and in those with adenocarcinoma was 83% and 63%, respectively (P = .04). Conclusions: Stage I bronchioloalveolar carcinoma is more likely to occur in nonsmokers. Survival is longer in patients with bronchioloalveolar carcinoma. Further research is warranted to define the etiology, clinical course, and molecular abnormalities in patients with bronchioloalveolar carcinoma to generate more effective therapeutic approaches. C1 Dana Farber Canc Inst, Dept Adult Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Div Expt Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Biostat Grp, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thorac Surg, Boston, MA 02115 USA. RP Breathnach, OS (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Lowe Ctr Thorac Oncol, Dana 1234,44 Binney St, Boston, MA 02115 USA. NR 34 TC 56 Z9 65 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2001 VL 121 IS 1 BP 42 EP 47 DI 10.1067/mtc.2001.110190 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 394PJ UT WOS:000166532200006 PM 11135158 ER PT J AU Roemer, L Litz, BT Orsillo, SM Wagner, AW AF Roemer, L Litz, BT Orsillo, SM Wagner, AW TI A preliminary investigation of the role of strategic withholding of emotions in PTSD SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE PTSD; emotions; veterans; suppression ID POSTTRAUMATIC-STRESS-DISORDER AB Individuals with posttraumatic stress disorder (PTSD) experience deficits in emotional responding, yet to date these deficits have been poorly understood. This study is an initial investigation of the role of strategic, intentional withholding of emotional responses among individuals with PTSD. In a sample of 61 combat veterans, veterans with PTSD reported significantly more frequent and intense withholding of their emotional responses than did combat veterans without PTSD. The tendency to withhold emotional responses was associated with PTSD, beyond measures of comorbid distress. The implications of these findings for future research and interventions aimed at deficits in emotional responding tire discussed. C1 Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. VA Med Ctr, Boston Dept, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. RP Roemer, L (reprint author), Univ Massachusetts, Dept Psychol, 100 Morrissey Blvd, Boston, MA 02125 USA. OI Roemer, Lizabeth/0000-0002-2453-5435 NR 21 TC 45 Z9 48 U1 2 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JAN PY 2001 VL 14 IS 1 BP 149 EP 156 DI 10.1023/A:1007895817502 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 563XH UT WOS:000176282900010 ER PT J AU D'Amico, AV Wu, YH Chen, MH Nash, M Renshaw, AA Richie, JP AF D'Amico, AV Wu, YH Chen, MH Nash, M Renshaw, AA Richie, JP TI Perineural invasion as a predictor of biochemical outcome following radical prostatectomy for select men with clinically localized prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; prostatectomy; outcome and process assessment (health care) ID BEAM RADIATION-THERAPY; NEEDLE-BIOPSY; EXTRAPROSTATIC EXTENSION; MULTIVARIATE-ANALYSIS; ANTIGEN RECURRENCE; PATHOLOGICAL STAGE; DISEASE RECURRENCE; ADENOCARCINOMA; NOMOGRAM; FAILURE AB Purpose: The presence of perineural invasion on the prostate needle biopsy specimen has been suggested to be an independent predictor of prostate specific antigen (PSA) outcome following radical prostatectomy. We evaluated the clinical use of perineural invasion at biopsy for predicting time to PSA failure following radical prostatectomy after controlling for established prognostic factors. Materials and Methods: A prospective evaluation using a Cox regression multivariate analysis of 750 men with clinically localized or PSA detected prostate cancer was performed to evaluate the ability of PSA, biopsy Gleason score, perineural invasion on the needle biopsy specimen and the percent of positive prostate biopsies to predict PSA outcome following radical prostatectomy. Results: Multivariate analysis demonstrated that the presence of perineural invasion on the needle biopsy specimen provided additional information regarding 5-year PSA outcome (82% versus 95%, p = 0.04) for patients who were in the low risk group. This difference in PSA outcome could be explained by higher rates of positive surgical margins (25% versus 17%, p = 0.07). Patients whose prostate needle biopsy contained perineural invasion and who had the corresponding neurovascular bundle resected had a significantly lower positive margin rate (11% versus 100%, p = 0.001) compared to those who had the neurovascular bundle spared. The presence of perineural invasion on biopsy was not a significant predictor of PSA outcome following radical prostatectomy for patients in the intermediate or high risk group. Conclusions: Resection of the neurovascular bundle on the side corresponding to location of perineural invasion on the biopsy may decrease the positive surgical margin rate and improve outcome for low risk patients. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 26 TC 53 Z9 56 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2001 VL 165 IS 1 BP 126 EP 129 DI 10.1097/00005392-200101000-00031 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 381HK UT WOS:000165756300036 PM 11125380 ER PT J AU Lovelace, TD Moneta, GL Abou-Zamzam, AM Edwards, JM Yeager, RA Landry, GJ Taylor, LM Porter, JM AF Lovelace, TD Moneta, GL Abou-Zamzam, AM Edwards, JM Yeager, RA Landry, GJ Taylor, LM Porter, JM TI Optimizing duplex follow-up in patients with an asymptomatic internal carotid artery stenosis of less than 60% SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID NATURAL-HISTORY; COST-EFFECTIVENESS; DISEASE; ENDARTERECTOMY; PREVALENCE; ATHEROSCLEROSIS; PROGRESSION AB Objectives: The Asymptomatic Carotid Atherosclerosis Study established benefit of carotid endarterectomy for 60% to 99% asymptomatic internal carotid artery (ICA) stenosis. Optimal follow-up intervals to detect progression from < 60% to 60%-99% ICA stenosis are unknown. In a previous study from our laboratory, we found that ICAs with < 60% stenosis and peak systolic velocities (PSVs) of 175 cm/s or more on initial duplex were at high risk for progression. Prospective evaluation of this hypothesis and determination of optimal duplex follow-up intervals for asymptomatic patients with < 60% ICA stenosis form the basis of this report. Methods: All patients who underwent initial carotid duplex examination for any indication since January 1, 1995, with at least one patent, asymptomatic, previously nonoperated ICA with < 60% stenosis; with 6 months' or greater follow-up; and with one or more repeat duplex examinations were entered into the study. On the basis of the initial duplex examination, ICAs were classified into two groups: those with a PSV less than 175 cm/s and those with a PSV of 175 cm/s or more. Follow-up duplex examinations were performed at varying intervals to detect progression from < 60% to 60%-99% ICA stenosis with criteria previously reported (both PSV 260 cm/s and end-diastolic velocity greater than or equal to 70 cm/s). Results: A total of 407 patients (640 asymptomatic ICAs with < 60% stenosis) underwent serial duplex scans (mean follow up, 22 months). Three ICAs (0.5%) became symptomatic and progressed to 60%-99% ICA stenosis at a mean of 21 months (all transient ischemic attacks), whereas four other ICAs occluded without stroke during follow-up. Progression to 60%-99% stenosis without symptoms was detected in 46 ICAs (7%) (mean, 18 months). Of the 633 patent asymptomatic arteries, 548 ICAs (87%) had initial PSVs less than 175 cm/s, and 85 ICAs (13%) had initial PSVs of 175 cm/s or more. Asymptomatic progression to 60%-99% ICA stenosis occurred in 22 (26%) of 85 ICAs with initial PSVs of 175 cm/s or more, whereas 24 (4%) of 548 ICAs with initial PSVs less than 175 cm/s progressed (P < .0001). The Kaplan-Meier method was used to determine freedom from progression at 6 months, 12 months, and 24 months, which was 95%, 83%, and 70% for ICAs with initial PSVs of 175 cm/s or more versus 100%, 99%, and 95%, respectively, for ICAs with initial PSVs less than 175 cm/s (P < .0001). Conclusions: Patients with < 60% ICA stenosis and PSVs of 175 cm/s or more on initial duplex examination are significantly more likely to progress asymptomatically to 60%-99% ICA stenosis, and progression is sufficiently frequent to warrant follow-up duplex studies at 6-month intervals. Patients with < 60% ICA stenosis and initial PSVs less than 175 cm/s may have follow-up duplex examinations safely deferred for 2 years. C1 Oregon Hlth Sci Univ, Div Vasc Surg, Dept Surg, Portland VA Med Ctr, Portland, OR 97201 USA. RP Moneta, GL (reprint author), Oregon Hlth Sci Univ, Div Vasc Surg, Dept Surg, Portland VA Med Ctr, OP-11,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. FU NCRR NIH HHS [RR00334]; NHLBI NIH HHS [1RO1HL45267-08A1] NR 20 TC 13 Z9 14 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2001 VL 33 IS 1 BP 56 EP 61 DI 10.1067/mva.2001.112303 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 395JH UT WOS:000166576900014 PM 11137924 ER PT J AU Dimitri, PS Wall, C Oas, JG Rauch, SD AF Dimitri, PS Wall, C Oas, JG Rauch, SD TI Application of multivariate statistics to vestibular testing: Discriminating between Meniere's disease and migraine associated dizziness SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article DE vestibulo-ocular reflex; time constant; decision analysis; Meniere's disease; migraine ID HARMONIC ACCELERATION; OCULAR REFLEX; TEMPORAL BONE; RESPONSES AB Meniere's disease (MD) and migraine associated dizziness (MAD) are two disorders that can have similar symptomatologies, but differ vastly in treatment. Vestibular testing is sometimes used to help differentiate between these disorders, but the inefficiency of a human interpreter analyzing a multitude of variables independently decreases its utility. Our hypothesis was that we could objectively discriminate between patients with MD and those with MAD using select variables from the vestibular test battery. Sinusoldal harmonic acceleration test variables were reduced to three vestibuto-ocular reflex physiologic parameters: gain, time constant, and asymmetry. A combination of these parameters plus a measurement of reduced vestibular response from caloric testing allowed us to achieve a joint classification rate of 91%, by use of a multivariate independent quadratic classification algorithm. Data from posturography were not useful for this type of differentiation. Overall, our classification function can be used as an unbiased assistant to discriminate between MD and MAD and gave us insight into the pathophysiologic differences between the two disorders. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Wall, C (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, 243 Charles St, Boston, MA 02114 USA. RI Oas, John/E-3772-2011 FU NIDCD NIH HHS [DC00290, DC03219] NR 28 TC 18 Z9 19 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2001 VL 11 IS 1 BP 53 EP 65 PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 507EJ UT WOS:000173013800005 PM 11673678 ER PT J AU Wall, C Assad, A Aharon, G Dimitri, PS Harris, LR AF Wall, C Assad, A Aharon, G Dimitri, PS Harris, LR TI The human oculomotor response to simultaneous visual and physical movements at two different frequencies SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article DE vestibular; self motion; translation; non-linear processing; optic flow ID VESTIBULE-OCULAR REFLEX; LINEAR ACCELERATION; VIEWING DISTANCE; Z-AXIS; MOTION AB In order to investigate interactions in the visual and vestibular systems' oculomotor response to linear movement, we developed a two-frequency stimulation technique. Thirteen subjects lay on their backs and were oscillated sinusoidally along their z-axes at between 0.31 and 0.81 Hz. During the oscillation subjects viewed a large, high-contrast, visual pattern oscillating in the same direction as the physical motion but at a different, non-harmonic ally related frequency. The evoked eye movements were measured by video-oculography and spectrally analysed. We found significant signal level at the sum and difference frequencies as well as at other frequencies not present in either stimulus. The emergence of new frequencies indicates non-linear processing consistent with an agreement-detector system that have previously proposed. C1 York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Harris, LR (reprint author), York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada. FU NIDCD NIH HHS [R01DC0290] NR 24 TC 3 Z9 3 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2001 VL 11 IS 2 BP 81 EP 89 PG 9 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 530AT UT WOS:000174334000003 PM 11847452 ER PT J AU Dimitri, PS Wall, C Rauch, SD AF Dimitri, PS Wall, C Rauch, SD TI Multivariate vestibular testing: Thresholds for bilateral Meniere's disease and aminoglycoside ototoxicity SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article DE vestibular testing; decision analysis; Meniere's disease; ototoxicity; unilateral vestibular hypofunction; bilateral vestibular hypofunction ID OCULAR REFLEX AB Although patient symptoms and an audiogram can typically identify the affected ear or ears in Meniere's disease, there are some cases where this differentiation is problematic. This paper concentrates on the sole use of vestibular test data to discriminate between unilateral and bilateral Meniere's disease. Patients that were known to have peripheral unilateral vestibular hypofunction (n = 104) were used as learning groups to define a region in multidimensional measurement space consisting of four vestibular test scores which summarized data from electronystagmography, sinusoidal harmonic acceleration and computerized dynamic posturography tests, A multivariate boundary was created from the unilateral learning group that determined thresholds for identifying bilateral vestibular hypofunction. Patients with bilateral Meniere's disease (n = 23) and with bilateral ototoxicity (n = 19) were then used as test subjects to determine the sensitivity of the multivariate boundary. Results showed up to a increase in estimated test sensitivity (specificity = 95%) from 67% (current method) to 82% (new method) in identifying bilateral vestibular hypofunction. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02115 USA. RP Wall, C (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC03219, DC00290] NR 33 TC 6 Z9 6 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2001 VL 11 IS 6 BP 391 EP 404 PG 14 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 630PL UT WOS:000180117100005 PM 12446964 ER PT J AU Dimitri, PS Wall, C Rauch, SD AF Dimitri, PS Wall, C Rauch, SD TI Multivariate vestibular testing: Laterality of unilateral Meniere's disease SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article DE vestibular testing; Meniere's disease; decision analysis; unilateral vestibular hypofunction ID NYSTAGMUS AB This paper discusses the use of vestibular testing to discriminate between right (n = 29) and left (n = 27) Meniere's disease. We examined reduced vestibular response (RVR), directional preponderance, and spontaneous and positional nystagmus measurements from electronystagmography, as well as the asymmetry measurements from the sinusoidal harmonic acceleration test, to determine whether multivariate logistic regression could improve upon the discrimination performance of RVR alone. We found that patients with a spontaneous or positional nystagmus often had a "recovery nystagmus", beating in the opposite direction of that predicted for an acute lesion. When present, the direction and magnitude of such nystagmus could be used in the classification algorithm to increase the discriminatory power over RVR alone, but in these patients the rotation test asymmetry measurements were rendered useless, In the absence of spontaneous or positional nystagmus, asymmetry measurements significantly enhanced right/left discrimination, Directional preponderance was insignificant in determining the side of lesion. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02115 USA. RP Wall, C (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC00290, DC03219] NR 11 TC 9 Z9 9 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2001 VL 11 IS 6 BP 405 EP 412 PG 8 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 630PL UT WOS:000180117100006 PM 12446965 ER PT J AU Sarukhan, A Camugli, S Gjata, B von Boehmer, H Danos, O Jooss, K AF Sarukhan, A Camugli, S Gjata, B von Boehmer, H Danos, O Jooss, K TI Successful interference with cellular immune responses to immunogenic proteins encoded by recombinant viral vectors SO JOURNAL OF VIROLOGY LA English DT Article ID ADENOASSOCIATED VIRUS VECTORS; COAGULATION FACTOR-IX; GENE-TRANSFER; T-CELLS; B-CELLS; IMMUNOCOMPETENT MICE; ADENOVIRUS VECTORS; CROSS-PRESENTATION; DENDRITIC CELLS; SKELETAL-MUSCLE AB Vectors derived from the adeno-associated virus (AAV) have been successfully used for the long-term expression of therapeutic genes in animal models and patients. One of the major advantages of these vectors is the absence of deleterious immune responses following gene transfer. However, AAV vectors, when used in vaccination studies, can result in efficient humoral and cellular responses against the transgene product. It is therefore important to understand the factors which influence the establishment of these immune responses in order to design safe and efficient procedures for AAV-based gene therapies. We have compared T-cell activation against a strongly immunogenic protein, the influenza virus hemagglutinin (HA), which is synthesized in skeletal muscle following gene transfer with an adenovirus (Ad) or an AAV vector, In both cases, cellular immune responses resulted in the elimination of transduced muscle fibers within 4 weeks. However, the kinetics of CD4(+) T-cell activation were markedly delayed when AAV vectors were used. Upon recombinant Ad (rAd) gene transfer, T cells were activated both by direct transduction of dendritic cells and by cross-presentation of the transgene product, while upon rAAV gene transfer T cells were only activated by the latter mechanism. These results suggested that activation of the immune system by the transgene product following rAAV-mediated gene transfer might be easier to control than that following rAd-mediated gene transfer. Therefore, we tested protocols aimed at interfering with either antigen presentation by blocking the CD40/CD40L pathway or with the T-cell response by inducing transgene-specific tolerance. Long-term expression of the AAV-HA was achieved in both cases, whereas immune responses against Ad-HA could not be prevented. These data clearly underline the importance of understanding the mechanisms by which vector-encoded proteins are recognized by the immune system in order to specifically interfere with them and to achieve safe and stable gene transfer in clinical trials. C1 Genethon III, F-91002 Evry, France. INSERM 345, Inst Necker, Paris, France. Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. RP Jooss, K (reprint author), Genethon III, 1 Rue Int, F-91002 Evry, France. NR 41 TC 93 Z9 96 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2001 VL 75 IS 1 BP 269 EP 277 DI 10.1128/JVI.75.1.269-277.2001 PG 9 WC Virology SC Virology GA 383BR UT WOS:000165863000031 PM 11119597 ER PT J AU DeBiasi, RL Edelstein, CL Sherry, B Tyler, KL AF DeBiasi, RL Edelstein, CL Sherry, B Tyler, KL TI Calpain inhibition protects against virus-induced apoptotic myocardial injury SO JOURNAL OF VIROLOGY LA English DT Article ID REOVIRUS-INDUCED APOPTOSIS; CENTRAL-NERVOUS-SYSTEM; DRUG-INDUCED APOPTOSIS; B-INDUCED DISEASE; VIRAL MYOCARDITIS; CARDIAC MYOCYTES; CELL-DEATH; NEUTROPHIL APOPTOSIS; T-CELLS; INFECTION AB Viral myocarditis is an important cause of human morbidity and mortality for which reliable and effective therapy is lacking. Using reovirus strain 8B infection of neonatal mice, a well-characterized experimental model of direct virus-induced myocarditis, we now demonstrate that myocardial injury results from apoptosis. Proteases play a critical role as effecters of apoptosis. The activity of the cysteine protease calpain increases in reovirus-infected myocardiocytes and can be inhibited by the dipeptide alpha-ketoamide calpain inhibitor Z-Leu-aminobutyric acid-CONH(CH2)3-morpholine (CX295). Treatment of reovirus-infected neonatal mice with CX295 protects them against reovirus myocarditis as documented by (i) a dramatic reduction in histopathologic evidence of myocardial injury, (ii) complete inhibition of apoptotic myocardial cell death as identified by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, (iii) a reduction in serum creatine phosphokinase, and (iv) improved weight gain. These findings are the first evidence for the importance of a calpain-associated pathway of apoptotic cell death in viral disease. Inhibition of apoptotic signaling pathways may be an effective strategy for the treatment of viral disease in general and viral myocarditis in particular. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat Infect Dis, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol & Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. N Carolina State Univ, Coll Vet Med, Dept Microbiol, Raleigh, NC 27606 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, 4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NHLBI NIH HHS [1RO1HL57161]; NIA NIH HHS [1RO1AG14071] NR 79 TC 70 Z9 78 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2001 VL 75 IS 1 BP 351 EP 361 DI 10.1128/JVI.75.1.351-361.2001 PG 11 WC Virology SC Virology GA 383BR UT WOS:000165863000038 PM 11119604 ER PT J AU Hioe, CE Chien, PC Lu, CF Springer, TA Wang, XH Bandres, J Tuen, M AF Hioe, CE Chien, PC Lu, CF Springer, TA Wang, XH Bandres, J Tuen, M TI LFA-1 expression on target cells promotes human immunodeficiency virus type 1 infection and transmission SO JOURNAL OF VIROLOGY LA English DT Article ID FUNCTION-ASSOCIATED MOLECULE-1; FUNCTION-ASSOCIATED ANTIGEN-1; SYNCYTIUM FORMATION; ADHESION MOLECULES; T-CELLS; NEUTRALIZATION; ICAM-1; ACTIN AB While CD4 and the chemokine receptors are the principal receptors for human immunodeficiency virus (HN), other cellular proteins, such as LFA-1, are also involved in HIV infection. LFA-1 end its ligands, ICAM-1, ICAM-2, and ICAM-3, can be expressed on the cells infected by HIV, as well as on the HIV virions themselves. To examine the role of LFA-1 expressed on target cells in HIV infection, Jurkat-derived J beta2.7 T-cell lines that express either wild-type LFA-1, a constitutively active mutant LFA-1, or no LFA-1 were used, The presence of wild-type LFA-1 enhanced the initial processes of HIV infection, as well as the subsequent replication and transmission from cell to cell. In contrast, the constitutively active LFA-1 mutant failed to promote virus replication and spread, even though this mutant could help HIV enter cells and establish the initial infection. This study clearly demonstrates the contribution of LFA-T in the different stages of HIV infection. Moreover, not only is LFA-1 expression important for initial HN-cell interaction, subsequent replication, and transmission, but its activity must also be properly regulated. C1 Vet Adm Med Ctr, Res Serv, New York, NY 10010 USA. NYU, Sch Med, New York, NY 10010 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hioe, CE (reprint author), Vet Adm Med Ctr, Res Serv, 423 E 23rd St,Room 18-124 N, New York, NY 10010 USA. FU NHLBI NIH HHS [HL59725, R01 HL059725]; NIAID NIH HHS [AI32424] NR 22 TC 55 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2001 VL 75 IS 2 BP 1077 EP 1082 DI 10.1128/JVI.75.2.1077-1082.2001 PG 6 WC Virology SC Virology GA 385QK UT WOS:000166015000057 PM 11134324 ER PT J AU Fried, LF Orchard, TJ Kasiske, BL AF Fried, LF Orchard, TJ Kasiske, BL CA Lipids Renal Dis Progression Meta-Anal TI Effect of lipid reduction on the progression of renal disease: A meta-analysis SO KIDNEY INTERNATIONAL LA English DT Article DE hyperlipidemia; nephropathy; progressive renal disease; proteinuria; albuminuria; glomerular filtration rate ID CHOLESTEROL-LOWERING THERAPY; DEPENDENT DIABETES-MELLITUS; DIETARY-PROTEIN RESTRICTION; REDUCES GLOMERULAR INJURY; SIMVASTATIN TREATMENT; NEPHROTIC SYNDROME; LONG-TERM; HYPERCHOLESTEROLEMIC PATIENTS; URINE SAMPLES; HUMAN-KIDNEY AB Background. It has been proposed that hyperlipidemia contributes to the progression of renal disease. A large trial has not been performed; however, a number of small, controlled trials have been reported. We examined the effects of antilipemic agents on glomerular filtration rate and proteinuria or albuminuria in patients with renal disease. Methods. We used Medline, abstracts from scientific meetings, and bibliographies from recent reviews and scientific reports to locate pertinent studies. Thirteen prospective con trolled trials examining the effects of antilipemic agents on renal function, proteinuria, or albuminuria were included. Studies were published as full reports or abstracts and were at least three months in duration. For five of the studies, individual patient data were obtained. Other summary data were independently extracted from the published reports by two investigators and included study quality, subject characteristics, cause of renal disease, change in serum cholesterol, blood pressure, glomerular filtration rate, proteinuria, and albuminuria. Results. There was a lower rate of decline in glomerular filtration rate with treatment compared with controls (treated controls, 0.156 mL/min/month; 95% CI, 0.026 to 0.285 mL/ min/month, P = 0.008). The study results were statistically homogeneous, and in a regression analysis, the effect of treatment on glomerular filtration rate did not correlate with study quality, the percentage change in cholesterol, the type of lipid-lowering agent, or the cause of renal disease. However, longer follow-up correlated with the amount of improvement in glomerular filtration rate from treatment (P = 0.007). There was a tendency for a favorable effect of treatment on protein or albumin excretion [Ln (treatment) - Ln (control) = -0.248, 95% CI, -0.562 to 0.064, P = 0.077]. However, these results were statistically heterogeneous between studies (P < 0.001). No obvious explanation for this heterogeneity was apparent in a regression analysis examining potential reasons for differences in study results. Conclusions. Lipid reduction may preserve glomerular filtration rate and may decrease proteinuria in patients with renal disease. C1 Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Med Serv, Renal Sect, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Hennepin Cty Med Ctr, Dept Med, Div Nephrol, Minneapolis, MN 55415 USA. RP Fried, LF (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, 938 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15213 USA. OI orchard, trevor/0000-0001-9552-3215 NR 49 TC 464 Z9 499 U1 0 U2 10 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2001 VL 59 IS 1 BP 260 EP 269 DI 10.1046/j.1523-1755.2001.00487.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 390KR UT WOS:000166294700029 PM 11135079 ER PT J AU Kesavan, S Rosenberg, AE Selig, MK Nielsen, GP AF Kesavan, S Rosenberg, AE Selig, MK Nielsen, GP TI The reclassification of MFH as fibrosarcoma: A proposal based on the analysis of the ultrastructural features of 100 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Singapore Gen Hosp, Singapore 0316, Singapore. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 59 BP 14A EP 14A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900072 ER PT J AU Nielsen, GP Fletcher, CDM Smith, M Rosenberg, AE AF Nielsen, GP Fletcher, CDM Smith, M Rosenberg, AE TI Soft tissue aneurysmal bone cyst. A clinicopathological study of 5 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. St Thomas Hosp, Dept Orthoped, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 73 BP 16A EP 16A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900086 ER PT J AU O'Connell, JX Nielsen, GP Ishida, T Kahn, L Fugunaga, M Rosenberg, AE AF O'Connell, JX Nielsen, GP Ishida, T Kahn, L Fugunaga, M Rosenberg, AE TI Insular and trabecular round cell sarcoma. A proposal for the recognition of a distinct bone neoplasm. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Surrey Mem Hosp, Surrey, BC, Canada. Tokyo Univ Hosp, Tokyo 113, Japan. Jikei Univ, Sch Med, Tokyo, Japan. Long Isl Jewish Med Ctr, New Hyde Park, NY 11042 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 75 BP 16A EP 16A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900088 ER PT J AU Rosenberg, AE Fletcher, CDM Nielsen, GP AF Rosenberg, AE Fletcher, CDM Nielsen, GP TI Intra-articular sarcomas: A study of 9 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 86 BP 18A EP 18A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900099 ER PT J AU Nasser, SM Polyak, K AF Nasser, SM Polyak, K TI Frequent allelic loss on chromosome 17q24-q25 in ductal carcinoma in situ (DCIS) of the breast. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 172 BP 32A EP 32A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900185 ER PT J AU Signoretti, S Monti, F Isaac, B Waltregny, D Dilks, J Gelman, R Pagano, M Loda, M AF Signoretti, S Monti, F Isaac, B Waltregny, D Dilks, J Gelman, R Pagano, M Loda, M TI The p27 ubiquitin ligase Skp2 is overexpressed in breast cancer. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 197 BP 37A EP 37A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900210 ER PT J AU Brogi, E Tambouret, R Bell, DA AF Brogi, E Tambouret, R Bell, DA TI Classification of benign endometrial cells in cervical smears from postmenopausal women on hormone replacement therapy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 272 BP 49A EP 49A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900285 ER PT J AU Elliott, DD Krane, JF Pitman, MB Pilch, BZ Faquin, WC AF Elliott, DD Krane, JF Pitman, MB Pilch, BZ Faquin, WC TI Fine needle aspiration biopsy (FNAB) of salivary gland basal cell tumors. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 284 BP 51A EP 51A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900297 ER PT J AU McKee, GT Mosher, R AF McKee, GT Mosher, R TI The significance of atypia in breast cyst fluid SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Faulkner Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 318 BP 57A EP 57A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900331 ER PT J AU Mohammadkhani, M Cooper, TL AF Mohammadkhani, M Cooper, TL TI Marginal zone lymphoma(MZL): A potential cause of false negative fine needle aspiration (FNA) diagnosis. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 324 BP 58A EP 58A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900337 ER PT J AU Mohammadkhani, M McKee, GT AF Mohammadkhani, M McKee, GT TI A potential pitfall in fine-needle aspiration (FNA) of axillary lymph node SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 323 BP 58A EP 58A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900336 ER PT J AU Nasser, SM Pitman, MB Pilch, BZ Glyptis, T Faquin, WC AF Nasser, SM Pitman, MB Pilch, BZ Glyptis, T Faquin, WC TI DNA topoisomerase II alpha expression in thyroid fine needle aspiration biopsies of benign and malignant follicular neoplasms. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 326 BP 58A EP 58A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900339 ER PT J AU Wieczorek, TJ Faquin, WC Rubin, BP Cibas, ES AF Wieczorek, TJ Faquin, WC Rubin, BP Cibas, ES TI Cytologic diagnosis of grastrointestinal stromal tumor (GIST) with emphasis on the differential diagnosis with leiomyosarcoma (LMS) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 363 BP 64A EP 64A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900376 ER PT J AU Wieczorek, TJ Krane, JF Domanski, HA Akerman, M Carlen, B Misdraji, J Granter, SR AF Wieczorek, TJ Krane, JF Domanski, HA Akerman, M Carlen, B Misdraji, J Granter, SR TI Cytologic findings in granular cell tumors, with emphasis on the diagnosis of malignant granular cell tumor by FNA SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Lund Hosp, S-22185 Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 362 BP 64A EP 64A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900375 ER PT J AU Busam, KJ Hester, K Sachs, D Ho, S Charles, C Zavislan, J Gonzalez, S Halpern, AC AF Busam, KJ Hester, K Sachs, D Ho, S Charles, C Zavislan, J Gonzalez, S Halpern, AC TI Detection of amelanotic cutaneous melanoma and evaluation of its margins by in vivo confocal scanning laser microscopy (CSLM) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 371 BP 66A EP 66A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900384 ER PT J AU Crowson, AN Mihm, MC Nash, J Magro, CM AF Crowson, AN Mihm, MC Nash, J Magro, CM TI The cutaneous manifestations of Crohn's disease in sites discontiguous from the involved gastrointestinal tract: A clinicopathological study of 28 patients. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Cent Med Labs, Winnipeg, MB, Canada. Reg Med Lab, Tulsa, OK USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 377 BP 67A EP 67A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900390 ER PT J AU Granter, SR McKee, PH Calonje, E Mihm, MC Busam, K AF Granter, SR McKee, PH Calonje, E Mihm, MC Busam, K TI Melanoma associated with blue nevus and melanoma mimicking cellular blue nevus: A clinicopathologic study of 10 cases on the spectrum of so-called "malignant blue nevus" SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Dermatopathol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Dermatopathol, Boston, MA USA. Massachusetts Gen Hosp, Div Dermatopathol, Boston, MA 02114 USA. St Thomas Hosp, St Johns Inst Dermatol, Div Dermatopathol, London, England. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 382 BP 67A EP 67A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900395 ER PT J AU Harris, K Duncan, L Tanabe, K Flotte, T AF Harris, K Duncan, L Tanabe, K Flotte, T TI Sentinel lymph nodes: Relative counts as an indication of melanoma metastasis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 384 BP 68A EP 68A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900397 ER PT J AU North, PE Waner, N Mizeracki, A Nicholas, R Kincannon, J Gibson, D Mihm, MC AF North, PE Waner, N Mizeracki, A Nicholas, R Kincannon, J Gibson, D Mihm, MC TI Placental antigens expressed by juvenile hemangioma (JH) are not present in other benign vascular proliferations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 403 BP 71A EP 71A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900416 ER PT J AU Faquin, WC Pitman, MB Barcus, ME Nasser, SM Pilch, BZ Glyptis, T Powers, CN AF Faquin, WC Pitman, MB Barcus, ME Nasser, SM Pilch, BZ Glyptis, T Powers, CN TI Measurement of DNA topoisomerase II alpha expression differentiates benign from malignant Hurthle cell neoplasms of the thyroid. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 430 BP 75A EP 75A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900443 ER PT J AU Gallagher, LA Pilch, BZ Gaz, RD Randolph, GW Faquin, WC AF Gallagher, LA Pilch, BZ Gaz, RD Randolph, GW Faquin, WC TI Histologic and clinicopathologic features of 31 medullary microcarcinomas and their precursors. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 433 BP 76A EP 76A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900446 ER PT J AU Rosenberg, AE Nielsen, GP Lauwers, GY Yantiss, RK AF Rosenberg, AE Nielsen, GP Lauwers, GY Yantiss, RK TI Reactive nodular fibrous pseudotumor of the gastrointestinal tract: A clinicopathological study of four cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 542 BP 94A EP 94A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900555 ER PT J AU Yantiss, RK Farraye, FA Chang, HK Compton, CC Odze, RD AF Yantiss, RK Farraye, FA Chang, HK Compton, CC Odze, RD TI Prognostic significance of acinar cell differentiation in pancreatic endocrine tumors (PET). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 572 BP 99A EP 99A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900585 ER PT J AU Amin, MB Young, RH Scully, RE AF Amin, MB Young, RH Scully, RE TI Large cell hyalinizing sertoli cell tumor or the testis: A distinctive estrogenic tumor of boys with Peutz-Jeghers syndrome (PJS): A report of six cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Emory Univ Hosp, Atlanta, GA 30322 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 580 BP 100A EP 100A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900593 ER PT J AU Hatzianastassiou, DK Young, RH Srigley, JR Ulbright, TM AF Hatzianastassiou, DK Young, RH Srigley, JR Ulbright, TM TI Unusual patterns of differentiation in Leydig cell tumors of the testis. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Indiana Univ, Indianapolis, IN 46204 USA. Army Gen Hosp 401, Athens, Greece. Massachusetts Gen Hosp, Boston, MA 02114 USA. McMaster Univ, Hamilton, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 639 BP 110A EP 110A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900652 ER PT J AU Henley, JD Young, RH Ulbright, TM AF Henley, JD Young, RH Ulbright, TM TI Clear cell sex cord-stromal tumors of the testis: A mimicker of seminoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Indiana Univ Hosp, Dept Pathol, Indianapolis, IN 46202 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 640 BP 110A EP 110A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900653 ER PT J AU Krishnan, B Smith, V Lechago, J Chen, Z Truong, L AF Krishnan, B Smith, V Lechago, J Chen, Z Truong, L TI Mast cells in renal epithelial neoplasm's (REN), identification and significance. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Dept Pathol, VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 662 BP 114A EP 114A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900675 ER PT J AU Kukoski, R Macri, E Renshaw, AA Hoffman, M Loda, M Datta, MW AF Kukoski, R Macri, E Renshaw, AA Hoffman, M Loda, M Datta, MW TI Functional sequestration of p27 by cyclin D2 leads to cyclin activation in testicular germ cell tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. Baptist Hosp Miami, Miami, FL USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Tumor Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 665 BP 115A EP 115A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900678 ER PT J AU McGregor, DK Ayala, G Krishnan, B Truong, L AF McGregor, DK Ayala, G Krishnan, B Truong, L TI Diagnosing primary and metastatic renal cell carcinoma (RCC), the use of the renal cell carcinoma marker (RMa). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 678 BP 117A EP 117A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900691 ER PT J AU McKenney, JK Amin, MB Srigley, JR Ro, JY Jimenez, R Grignon, DJ Young, RH AF McKenney, JK Amin, MB Srigley, JR Ro, JY Jimenez, R Grignon, DJ Young, RH TI Adenoid basal proliferations of the prostate other than usual basal cell hyperplasia: A study of 23 cases with a proposed classification. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. Credit Valley Hosp, Mississauga, ON, Canada. Wayne State Univ, Detroit, MI USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 680 BP 117A EP 117A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900693 ER PT J AU Oliva, E Amin, MB Jimenez, R Young, RH AF Oliva, E Amin, MB Jimenez, R Young, RH TI Clear cell carcinoma (CCC) of the urinary bladder: A report of thirteen cases with emphasis on its histogenesis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Emory Univ Hosp, Dept Pathol, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 691 BP 119A EP 119A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900704 ER PT J AU Osipov, V Keating, JT Faul, P Loda, M Datta, MW AF Osipov, V Keating, JT Faul, P Loda, M Datta, MW TI The expression of p27 and VHL in renal tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 693 BP 119A EP 119A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900706 ER PT J AU Piris, A Velaquez, EF Cubilla, AL AF Piris, A Velaquez, EF Cubilla, AL TI Continuous sequence of Squamous Hyperplasia and low grade invasive squamous cell carcinoma (SCC) of the penis suggests a causal link. A report of 30 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Patol & Invest, Asuncion, Paraguay. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 699 BP 120A EP 120A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900712 ER PT J AU Tamboli, P Amin, MB Eble, JN Young, RH AF Tamboli, P Amin, MB Eble, JN Young, RH TI Histologic spectrum of glandular neoplasms of the urachus, with special emphasis on low-grade tumors. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Indiana Univ Hosp, Indianapolis, IN 46202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 722 BP 124A EP 124A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900735 ER PT J AU Velazquez, EF Cubilla, APAL AF Velazquez, EF Cubilla, APAL TI High grade squamous intraepithelial lesion (HGSIL) of the penis: Morphological subtypes correlates with homologous variants of invasive squamous cell carcinomas (SCC). A report of 126 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Inst Patol & Invest, Asuncion, Paraguay. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 736 BP 126A EP 126A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900749 ER PT J AU Velazquez, EF Piris, A Cubilla, AL AF Velazquez, EF Piris, A Cubilla, AL TI Correlation of lichen sclerosus (LS) with histological types of penile squamous cell carcinoma (SCC) and giant condylomas. A study of 61 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Inst Patol & Invest, Asuncion, Paraguay. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 737 BP 127A EP 127A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900750 ER PT J AU Weinstein, M Signoretti, S Loda, M AF Weinstein, M Signoretti, S Loda, M TI Diagnostic utility of p63 staining of prostate needle biopsies. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 742 BP 127A EP 127A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900755 ER PT J AU Wu, CL Chakravarti, A Delaney, M Zietman, AL Shipley, WU Hammond, EH AF Wu, CL Chakravarti, A Delaney, M Zietman, AL Shipley, WU Hammond, EH TI Loss of p16 protein expression correlates with Gleason scores and distant metastasis prostate cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Univ Utah, Sch Med, Massachusetts & LDS Hosp, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 745 BP 128A EP 128A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900758 ER PT J AU Wu, CL Cheng, L AF Wu, CL Cheng, L TI Quantification of spermine in intact human prostate specimens SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 744 BP 128A EP 128A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900757 ER PT J AU Baergen, RN Rutgers, JL Young, RH AF Baergen, RN Rutgers, JL Young, RH TI Extrauterine lesions of intermediate trophoblast (ELIT). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. Univ Calif Irvine, Long Beach Mem Med Ctr, Long Beach, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 774 BP 133A EP 133A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900787 ER PT J AU Bell, DA Mok, S AF Bell, DA Mok, S TI p53 and c-erbB2 overexpression in microscopic ovarian carcinomas. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 775 BP 133A EP 133A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900788 ER PT J AU Fan, MJ Sung, R Oliva, E Young, RH Scully, RE AF Fan, MJ Sung, R Oliva, E Young, RH Scully, RE TI Morphologic spectrum and differential diagnosis of 63 ovarian smooth muscle tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 794 BP 136A EP 136A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900807 ER PT J AU Fan, MJ Sung, R Oliva, E Young, RH Scully, RE AF Fan, MJ Sung, R Oliva, E Young, RH Scully, RE TI Spindle cell ovarian smooth muscle tumors: A study of 53 cases evaluating prognostic criteria SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 795 BP 136A EP 136A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900808 ER PT J AU Murray, SK Young, RH Scully, RE AF Murray, SK Young, RH Scully, RE TI Uterine endometrioid carcinoma with small non-villous papillae: An analysis of 26 cases of a favorable-prognosis tumor to be distinguished from serous carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 826 BP 141A EP 141A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900839 ER PT J AU Oliva, E Amin, MB Murray, SK Young, RH Scully, RE AF Oliva, E Amin, MB Murray, SK Young, RH Scully, RE TI Endometrial stromal and smooth muscle tumors of the uterus; Do they have distinctive immunohistochemical profiles? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 831 BP 142A EP 142A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900844 ER PT J AU Pitman, MB Cibas, E Powers, CN Frable, WJ AF Pitman, MB Cibas, E Powers, CN Frable, WJ TI Consequence of eliminating ASCUS SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pathol, Richmond, VA 23298 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 838 BP 143A EP 143A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900851 ER PT J AU Krane, JF McKeon, F Faquin, WC AF Krane, JF McKeon, F Faquin, WC TI Expression of p63, a p53 homologue, in normal and neoplastic salivary gland (SG) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 881 BP 151A EP 151A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900894 ER PT J AU de Leval, L Braaten, KM Harris, NL AF de Leval, L Braaten, KM Harris, NL TI Primary large B-cell lymphoma of bone: A B-cell neoplasm with a predominantly germinal-center(GC)-like immunophenotype. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 939 BP 160A EP 160A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900952 ER PT J AU Dong, HY Shahsafaei, A Dorfman, DM AF Dong, HY Shahsafaei, A Dorfman, DM TI CD27 and CD148 are expressed in B cell lymphomas derived from both memory and naive B cells. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 943 BP 161A EP 161A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900956 ER PT J AU Du, MQ Liu, H Diss, TC Hamoudi, RA Cabecadas, J Dong, HY Harris, N Isaacson, PG AF Du, MQ Liu, H Diss, TC Hamoudi, RA Cabecadas, J Dong, HY Harris, N Isaacson, PG TI KSHV positive germinotropic lymphoma: A new KSHV associated lymphoproliferative disorder SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 UCL Royal Free & Univ Coll Med Sch, Dept Histopathol, London, England. Inst Canc Res, Gene Cloning Ctr, Sutton, Surrey, England. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 946 BP 161A EP 161A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634900959 ER PT J AU Lauwers, GY Terris, B Batts, KP Chang, Y Yamabe, H Belghiti, J Nagorney, DM Flejou, JF Yamaoka, Y Vauthey, JN AF Lauwers, GY Terris, B Batts, KP Chang, Y Yamabe, H Belghiti, J Nagorney, DM Flejou, JF Yamaoka, Y Vauthey, JN TI Prognostic histologic determinants of resected hepatocellular carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hop Beaujon, Paris, France. Mayo Clin, Rochester, MN USA. Kyoto Univ, Kyoto, Japan. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 1169 BP 199A EP 199A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634901182 ER PT J AU Wu, CL Kirley, S Zukerberg, LR AF Wu, CL Kirley, S Zukerberg, LR TI Cables is a novel cell cycle regulatory protein SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 1253 BP 213A EP 213A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634901266 ER PT J AU Quade, BJ Lemyre, E Bruns, GAP Gusella, JF Korf, BR Herrick, SR Ligon, AH Lewis, J Maas, RL Michelson, AM Morton, CC AF Quade, BJ Lemyre, E Bruns, GAP Gusella, JF Korf, BR Herrick, SR Ligon, AH Lewis, J Maas, RL Michelson, AM Morton, CC TI Developmental Genome Anatomy Project: Two breakpoints localized in large insert genomic clones. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 1265 BP 215A EP 215A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634901278 ER PT J AU Matsubara, O Imazeki, N Okochi, Y Ozeki, Y Mark, EJ AF Matsubara, O Imazeki, N Okochi, Y Ozeki, Y Mark, EJ TI Vascular endothelial growth factor and thrombospondin-1 in diffuse alveolar damage and advanced pulmonary fibrosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 1318 BP 223A EP 223A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634901331 ER PT J AU Lindeman, N Waltregny, D Signoretti, S Loda, M AF Lindeman, N Waltregny, D Signoretti, S Loda, M TI Rapid immunostaining of frozen sections: A tool for laser capture microdissection and quantitative RT-PCR SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2001 VL 81 IS 1 MA 1378 BP 233A EP 233A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 396KE UT WOS:000166634901391 ER PT S AU Pfefer, TJ Schomacker, KT Nishioka, NS AF Pfefer, TJ Schomacker, KT Nishioka, NS BE Duncan, DD Jacques, SL Johnson, PC TI Effect of fiber optic probe design on fluorescent light propagation in tissue SO LASER-TISSUE INTERACTION XII: PHOTOCHEMICAL, PHOTOTHERMAL, AND PHOTOMECHANICAL SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Laser-Tissue Interaction XII - Photochemical, Photothermal, and Photomechanical CY JAN 21-24, 2001 CL SAN JOSE, CA SP USAF Off Sci Res, SPIE DE fluorescence spectroscopy; numerical modeling; fiber optic probe; Monte Carlo ID LASER-INDUCED FLUORESCENCE; HUMAN COLON TISSUE; IN-VIVO; TURBID MEDIA; AUTOFLUORESCENCE; DIAGNOSIS; SPECTROSCOPY; SKIN; ESOPHAGUS; DYSPLASIA AB Fiber optic probes used to deliver and collect light for biomedical fluorescence spectroscopy applications have varied widely in design. Critical design parameters include fiber diameter, tissue-fiber tip spacing, and illumination-collection fiber separation distance. While device design has been shown to influence spectral distributions, previous studies have not thoroughly addressed how probe geometry affects the spatial origin of detected fluorescence or how probe design night be customized for specific tissue sites or applications. We have developed a Monte Carlo model of laser-induced fluorescence and investigated the effect of design parameters on light propagation using gastrointestinal tissue optical properties. The distribution of emission locations for detected fluorescence were calculated. Initial results indicated that average fluorescence emission depth and total signal intensity are highly dependent on fiber size and tissue-fiber spacing. The implications of these results for the optimization of probes used in the detection of neoplasia are discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. EM nnishioka@partners.org NR 31 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3935-5 J9 PROC SPIE PY 2001 VL 4257 BP 410 EP 416 DI 10.1117/12.434727 PG 7 WC Engineering, Biomedical; Optics; Physics, Applied SC Engineering; Optics; Physics GA BS86T UT WOS:000171276900049 ER PT J AU Nikas, DC Foley, JW Black, PM AF Nikas, DC Foley, JW Black, PM TI Fluorescent imaging in a glioma model in vivo SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE fluorescence detection; benzo[a]phenoxazine; Nile blue; tumor demarcation; gliomas ID MALIGNANT GLIOMAS; MURINE SARCOMAS; BRAIN-TUMORS; BENZOPHENOTHIAZINE; CELLS; RESECTION; MARGINS; YIELDS AB Background and Objective: Nile blue dyes have been shown to have affinity for tumor tissue as compared to surrounding normal tissue and to be relatively non-toxic. We have employed EtNBA, a lipophilic, fluorescent benzophenoxazine dye, in a murine model to image subcutaneous and intracranial U-87 glioma implants. Study Design/Materials and Methods: The imaging system used to detect fluorescence consists of a SIT video camera fitted with a zoom microscope-magnifying lens. The tumor Suss illuminated with a 632.8-nm diffuse beam from a helium-neon laser. The video image was processed using a Sony image processor to give real-time pseudocolor and enhanced black and white images. Results: Following subcutaneous injection of the dye at doses of 2.5-5.0 mg/kg bw, we observed a gradual increase of the fluorescent signal from the tumor which peaked 1-3 hours post-injection with variable selectivity (typically 4:1) for tumor to normal surrounding tissues permitting the clear demarcation of the tumor. Conclusions: The present in vivo study demonstrates that EtNBA is a safe and effective photodiagnostic agent, able to demarcate U87-MG solid tumors in mice on a realtime basis at a concentration of 2.5-5.0 mg/kg 1-3 hours after administration. (C) 2001 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Ctr Neurosurg Sci,Brain Tumor Res Ctr, Brigham & Womens Hosp,Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Div Neurosurg, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Surg, Lebanon, NH 03756 USA. Rowland Inst Sci Inc, Cambridge, MA 02142 USA. RP Nikas, DC (reprint author), 30 Wolf Rd,Suite 312, Lebanon, NH 03766 USA. NR 28 TC 5 Z9 5 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2001 VL 29 IS 1 BP 11 EP 17 DI 10.1002/lsm.1079 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 458ZP UT WOS:000170225600002 PM 11500856 ER PT J AU Lee, S McAuliffe, DJ Kollias, N Flotte, TJ Doukas, AG AF Lee, S McAuliffe, DJ Kollias, N Flotte, TJ Doukas, AG TI Permeabilization and recovery of the stratum corneum in vivo: The synergy of photomechanical waves and sodium lauryl sulfate SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE drug delivery; shock waves; sodium lauryl sulfate; stratum corneum barrier; transdermal delivery ID TRANSDERMAL DRUG-DELIVERY; IN-VIVO; STRESS WAVES; SKIN; ELECTROPORATION; MODEL AB Background and Objective: Photomechanical waves render the stratum corneum permeable and allow macromolecules to diffuse into the epidermis and dermis. The aim of this study was to investigate the combined action of photomechanical waves and sodium lauryl sulfate, an anionic surfactant, for transdermal delivery. Study Design/Materials and Methods: A single photomechanical wave was applied to the skin of rats in the presence of sodium lauryl sulfate. The sodium lauryl sulfate solution was removed and aqueous solutions of rhodamine-B dextran (40 kDa molecular weight) were applied to the skin at time points 2, 30, and 60 minutes post-exposure. The presence of rhodamine-B dextran in the skin was measured by fluorescence emission spectroscopy in vivo and fluorescence microscopy of frozen biopsies. Results: The use of sodium lauryl sulfate delayed the recovery of the stratum corneum barrier and extended the time available for the diffusion of dextran through it. Conclusion: The combination of photomechanical waves and surfactants can enhance transdermal drug delivery. (C) 2001 Wiley-Liss, Inc. C1 Harvard Univ, Wellman Labs Photomed, Dept Dermatol, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Doukas, AG (reprint author), Harvard Univ, Wellman Labs Photomed, Dept Dermatol, Sch Med,Massachusetts Gen Hosp, 55 Fruit St,Mail Stop WEL224, Boston, MA 02114 USA. NR 21 TC 18 Z9 20 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2001 VL 29 IS 2 BP 145 EP 150 DI 10.1002/lsm.1101 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 467ED UT WOS:000170687700009 PM 11553902 ER PT J AU Altshuler, GB Anderson, RR Manstein, D Zenzie, HH Smirnov, MZ AF Altshuler, GB Anderson, RR Manstein, D Zenzie, HH Smirnov, MZ TI Extended theory of selective photothermolysis SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE photothermolysis; photoepilation; photosclerotherapy ID PORT-WINE STAINS; OPTICAL-PROPERTIES; LASER TREATMENT; BLOOD; RANGE; NM AB Background and Objective: We present a new theory of selective thermal damage of non-uniformly pigmented structures in biological tissues. Spatial separation of the heavily pigmented areas and the target requires limitation of the pigment temperature and heat diffusion from the pigmented to the targeted areas. Study Design/Materials and Methods: A concept of selective target damage by heat diffusion is presented for three target geometries: planar, cylindrical, and spherical. An in vitro experiment is described in which the dependence of thermal damage on pulsewidth at constant fluence was evaluated. Results: The in vitro experiment showed that the size of the damage zone for similar hair follicles was pulsewidth-independent over a very broad range of pulsewidths (30-400 ms). We formulated a new theory (extended theory of photothermolysis) to interpret the experimental results. Conclusions: Based on this new theory, the treatment pulsewidth for non-uniformly pigmented targets is significantly longer than the target thermal relaxation time (TRT). The theory provides new recommendations for photoepilation and photosclerotherapy parameters. Lasers Surg. Med. 29:416-432, 2001. (C) 2001 Wiley-Liss. Inc. C1 Palomar Med Technol Inc, Burlington, MA 01803 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Inst Fine Mech & Opt, St Petersburg 197101, Russia. RP Altshuler, GB (reprint author), Palomar Med Technol Inc, 82 Cambridge St, Burlington, MA 01803 USA. NR 11 TC 133 Z9 146 U1 1 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2001 VL 29 IS 5 BP 416 EP 432 DI 10.1002/lsm.1136 PG 17 WC Dermatology; Surgery SC Dermatology; Surgery GA 504DY UT WOS:000172843100004 PM 11891730 ER PT J AU Nigri, GR Tsai, S Kossodo, S Waterman, P Fungaloi, P Hooper, DC Doukas, AG LaMuraglia, GM AF Nigri, GR Tsai, S Kossodo, S Waterman, P Fungaloi, P Hooper, DC Doukas, AG LaMuraglia, GM TI Laser-induced shock waves enhance sterilization of infected vascular prosthetic grafts SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE biofilms; S. epidermidis; S. aureus ID STAPHYLOCOCCUS-EPIDERMIDIS; BACTERIAL BIOFILMS; STRESS WAVES; MICROBIAL BIOFILMS; DRUG-DELIVERY; IN-VITRO; ADHESION; MANAGEMENT; MEMBRANE AB Background and Objective: Bacteria that cause infection of vascular prosthetic grafts produce an exopolysaccharide matrix known as biofilm. Growth in biofilms protects the bacteria from leukocytes, antibodies and antimicrobial drugs, Laser-generated shock waves (SW) can disrupt biofilms and increase drug penetration. This study investigates the possibility of increasing antibiotic delivery and sterilization of vascular prosthetic graft, Study Design/Materials and Methods: Strains of Staphylococcus epidermidis and S. aureus were isolated From infected prosthetic grafts obtained directly from patients. Dacron grafts were inoculated with the isolated bacteria, which were allowed to form adherent bacterial colonies. The. colonized grafts underwent the following treatments: (a) antibiotic (vancomycin) alone; (b) antibiotic and SW (c) saline only: and (d) saline and SW. Six hours after treatment, the grafts were sonicated, the effluent was cultured and the colony forming units (CFU) were counted. Results: CFU recovered from control grafts colonized by S. epidermidis were comparable: saline, 3.05 x 10(8) and saline + SW 3.31 x 10(8). The number of S. epidermidis CFU diminished to 7.61 x 10(6) after antibiotic treatment but the combined antibiotic + SW treatment synergistically decreased CFU number to 1.27 x 10(4) (P < 0.001). S. aureus showed a higher susceptibility to the antibiotic: 2.26 x 10(6) CFU; antibiotic + SW treatment also had an incremental effect: 8.27 x 10(4) CFU (P < 0.001). Conclusions: This study demonstrates that laser-generated shock waves have no effects alone, but can enhance the effectiveness of antibiotics against bacteria associated with prosthetic vascular graft biofilms, suggesting that this treatment may be of value as adjunctive therapy for prosthetic graft infections. Lasers Surg. Med. 29:448-454, 2001. (C) 2001 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, WAV 464, Boston, MA 02114 USA. NR 30 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2001 VL 29 IS 5 BP 448 EP 454 DI 10.1002/lsm.1138 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 504DY UT WOS:000172843100007 PM 11891733 ER PT J AU Lee, S McAuliffe, DJ Mulholland, SE Doukas, AG AF Lee, S McAuliffe, DJ Mulholland, SE Doukas, AG TI Photomechanical transdermal delivery of insulin in vivo SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE protein delivery; shock waves; stress waves; transcutaneous drug delivery ID STRESS WAVES AB Background and Objective: Previous studies have shown that photomechanical waves transiently permeabilize the stratum corneum in vivo. The aim of the present work was to investigate the potential of photomechanical waves for systemic drug delivery. Study Design/Materials and Methods: Photomechanical waves were generated by ablation of a polystyrene target by a Q-switched ruby laser. Systemic insulin delivery in a streptozotocin-diabetic rat model was monitored by measuring the blood glucose level. Results: After photomechanical insulin delivery, the blood glucose decreased 80 +/- 3% and remained below 200 mg/dl for more than 3 hours. Whereas in control experiments (for which insulin was applied without photomechanical waves), there was no dramatic change in the blood glucose (standard deviation of measurements over 4 hours was 7%). Conclusion: The application of the photomechanical waves allowed similar to6-kDa protein molecules (insulin) to pass through the stratum corneum and into the systemic circulation. (C) 2001 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Doukas, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Mail Stop WEL224, Boston, MA 02114 USA. NR 11 TC 29 Z9 33 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2001 VL 28 IS 3 BP 282 EP 285 DI 10.1002/lsm.1052 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 419MU UT WOS:000167953500015 PM 11295766 ER PT J AU Lee, S McAuliffe, DJ Flotte, TJ Kollias, N Doukas, AG AF Lee, S McAuliffe, DJ Flotte, TJ Kollias, N Doukas, AG TI Photomechanical transdermal delivery: The effect of laser confinement SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE ablation; shock waves; stress waves; stratum corneum barrier; transcutaneous drug delivery ID GENERATED STRESS WAVES; STRATUM-CORNEUM; DRUG-DELIVERY; CELL-MEMBRANE; IN-VITRO; TRANSPORT; GRADIENT AB Background and Objectives: Photomechanical waves can transiently permeabilize the stratum corneum and facilitate the delivery of drugs into the epidermis and dermis. The present study was undertaken to assess the effect of pulse characteristics to the penetration depth of macromolecules delivered into the skin. Study Design/Materials and Methods: Photomechanical waves were generated by confined ablation with a Q-switched ruby laser. Fluorescence microscopy of frozen biopsies was used to assay the delivery of macromolecules through the stratum corneum and determine the depth of penetration. Results: Photomechanical waves generated by confined ablation of the target have a longer rise time and duration than those generated by direct ablation. Confined ablation required a lower radiant exposure (from similar to7 J/cm(2) to similar to5 J/cm(2)) for an increase in the depth of delivery (from similar to 50 mum to similar to 400 mum). Conclusions: Control of the characteristics of the photomechanical waves is important for transdermal delivery as they can affect the depth of drug penetration into the dermis. Lasers Surg. Med. 28:344-347, 2001. (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Doukas, AG (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St,Mail Stop WEL224, Boston, MA 02114 USA. NR 22 TC 41 Z9 44 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2001 VL 28 IS 4 BP 344 EP 347 DI 10.1002/lsm.1060 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 428LC UT WOS:000168462300008 PM 11344515 ER PT J AU Medzihradszky, KF Ambulos, NP Khatri, A Osapay, G Remmer, HA Somogyi, A Kates, SA AF Medzihradszky, KF Ambulos, NP Khatri, A Osapay, G Remmer, HA Somogyi, A Kates, SA TI Mass spectrometry analysis for the determination of side reactions for cyclic peptides prepared from an Fmoc/tBu/Dmab protecting group strategy SO LETTERS IN PEPTIDE SCIENCE LA English DT Article DE cyclic peptide; Dmab protecting group; low energy collision-induced dissociation; mass spectrometry; post source decay ID SOLID-PHASE SYNTHESIS; CHEMISTRY AB The Association of Biomolecular Resource Facilities (ABRF) Peptide Synthesis Research Group (PSRG) proposed for their annual study that laboratory members prepare cyclo(Tyr-Glu-Ala-Ala-Arg-DPhe-Pro-Glu-Asp-Asn) according to the following synthetic pathway: (i) side-chain anchoring Fmoc-Asp(OH)-ODmab to a Rink amide resin; (ii) linear assembly; (iii) Dmab and Fmoc removal, respectively; (iv) on-resin cyclization with an uronium-based coupling reagent; (v) final cleavage/deprotection with TFA. Based upon this protocol, a variety of side-products were identified: (i) N-terminal guanidine formation; (ii) C-terminal piperidyl amide formation; and (iii) a novel C-terminal benzyl amide-guanidine derivative that formed due to a chemical reaction between the Dmab protecting group and the uronium-based coupling agent. The elemental composition and subsequent structure determination of this unexpected derivative was established by tandem mass spectrometry, i.e. low energy collision-induced dissociation experiments with fragment mass determination within 5 ppm. C1 Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Univ Maryland Baltimore, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Irvine, Irvine, CA USA. Univ Illinois, Ctr Biotechnol, Urbana, IL 61801 USA. Univ Arizona, Tucson, AZ USA. Consensus Pharmaceut Inc, Medford, MA USA. NR 12 TC 2 Z9 2 U1 1 U2 11 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5666 J9 LETT PEPT SCI JI Lett. Pept. Sci. PY 2001 VL 8 IS 1 BP 1 EP 12 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 524EY UT WOS:000174000600001 ER PT J AU Stone, ME AF Stone, ME TI Coming out of cancer: Writings from the lesbian cancer epidemic. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JAN PY 2001 VL 126 IS 1 BP 140 EP 140 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 391XH UT WOS:000166381200254 ER PT J AU Jones, CL Harrington, DP AF Jones, CL Harrington, DP TI Omnibus tests of the martingale assumption in the analysis of recurrent failure time data SO LIFETIME DATA ANALYSIS LA English DT Article DE uncorrelated increments; recurrent events; martingale residual; multiplicative intensity model ID OF-FIT TESTS; REGRESSION-MODEL; RESIDUALS; GOODNESS AB The Andersen-Gill multiplicative intensity (MI) model is well-suited to the analysis of recurrent failure time data. The fundamental assumption of the MI model is that the process M-i(t) for subjects i=1,...,n, defined to be the difference between a subject's counting process and compensator, i.e., N-i(t) - A(i)(t); t>0, is a martingale with respect to some filtration. We propose omnibus procedures for testing this assumption. The methods are based on transformations of the estimated martingale residual process (M) over cap (i)(t) a function of consistent estimates of the log-intensity ratios and the baseline cumulative hazard. Under a correctly specified model, the expected value of (M) over cap (i)(t) is approximately equal to zero with approximately uncorrelated increments. These properties are exploited in the proposed testing procedures. We examine the effects of censoring and covariate effects on the operating characteristics of the proposed methods via simulation. The procedures are most sensitive to the omission of a time-varying continuous covariate. We illustrate use of the methods in an analysis of data from a clinical trial involving patients with chronic granulatomous disease. C1 Univ Texas, Houston Sch Publ Hlth, Houston, TX 77030 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jones, CL (reprint author), Univ Texas, Houston Sch Publ Hlth, 1200 Herman Pressler St,RAS E831, Houston, TX 77030 USA. FU NCI NIH HHS [CA-39929]; NIGMS NIH HHS [5 F31 GM17274-04] NR 27 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PY 2001 VL 7 IS 2 BP 157 EP 171 DI 10.1023/A:1011396706243 PG 15 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 433AP UT WOS:000168733400004 PM 11458655 ER PT J AU Leaf, A AF Leaf, A TI The electrophysiologic basis for the antiarrhythmic and anticonvulsant effects of n-3 polyunsaturated fatty acids: Heart and brain SO LIPIDS LA English DT Article; Proceedings Paper CT Workshop on Prevention and Treatment of Vascular Disease CY MAY 18-20, 2000 CL AARHUS, DENMARK ID RAT CARDIAC MYOCYTES; LONG-CHAIN; VENTRICULAR MYOCYTES; NA+ CHANNELS; PREVENTION; ARRHYTHMIAS; CURRENTS AB The n-3 polyunsaturated fatty acids (PUFA) have been shown to be antiarrhythmic in animals and probably in humans. PUFA stabilize the electrical activity of isolated cardiac myocytes by modulating sarcolemmal ion channels, so that a stronger electrical stimulus is required to elicit an action potential and the refractory period is markedly prolonged. Inhibition of voltage-dependent sodium currents, which initiate action potentials in excitable tissues and of the L-type calcium currents, which initiate release of sarcoplasmic calcium stores, thus increasing cytosolic free calcium concentrations and activating the contractile proteins in myocytes, appears at present to be the probable major antiarrhythmic mechanisms of PUFA. Because the ion channels in neurons have channel proteins essentially homologous to those in the heart, the n-3 fatty acids would appear to be likely to affect the electrical activity in the brain in a manner similar to their effects in the heart, and accumulating evidence supports this notion. Evidence of important beneficial neurological effects of dietary n-3 PUFA are emerging with more likely to be discovered. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, Bldg 149,Rm 4001,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL62284]; NIDDK NIH HHS [DK38165] NR 22 TC 37 Z9 39 U1 0 U2 0 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PY 2001 VL 36 SU S BP S107 EP S110 DI 10.1007/s11745-001-0691-y PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 519GW UT WOS:000173718100017 PM 11837982 ER PT J AU Choi, N Baumann, M Flentjie, M Kellokumpu-Lehtinen, P Senan, S Zamboglou, N Kosmidis, P AF Choi, N Baumann, M Flentjie, M Kellokumpu-Lehtinen, P Senan, S Zamboglou, N Kosmidis, P TI Predictive factors in radiotherapy for non-small cell lung cancer: present status SO LUNG CANCER LA English DT Article DE lung cancer; predictive factor; radiation therapy; radiation response ID THERAPY-ONCOLOGY-GROUP; ACCELERATED RADIATION-THERAPY; RANDOMIZED MULTICENTER TRIAL; CONVENTIONAL RADIOTHERAPY; BRONCHOGENIC-CARCINOMA; PHASE-III; IMPROVED SURVIVAL; FAILURE PATTERNS; DOSE-ESCALATION; CHEMOTHERAPY AB Purpose: To evaluate the predictive factors for radiation response in non-small cell lung cancer (NSCLC) and the role of such factors in guiding high dose radiation therapy. Methods: The first International Workshop on Prognostic and Predictive Factors in Lung Cancer was organized by the Hellenic Cooperative Oncology Group and held in Athens, Greece under the auspices of the International Association for the Study of Lung Cancer. Presentations at this meeting provided the outline of this report, which has also been supplemented with available data from the current literature. Results: The predictive factors for both the natural history and the therapy outcome of NSCLC are grouped as follows: (1) tumor related factors (anatomic factors); the extent of tumor (tumor stage) is one of most important prognostic Factors affecting the therapy outcome. Tumor size (T stage), anatomical structures involved (T4 vs. T3 lesion), and the presence of regional lymph node metastasis have a significant impact on both prognosis and response to appropriate therapy: (2) host-related factors (clinical factors) that are important in therapy response include performance status, weight loss of more than 10% of body weight in the previous 6 months, and associated co-morbidities, i.e. pulmonary and cardiac diseases; (3) technical factors of radiation therapy which play a decisive role in successful outcome. The target volume should be defined accurately using modern imaging studies. The radiation dose fractionation schedule, in terms of the dose intensity and total dose, should be high enough to provide local tumor control in the majority of patients. Three-dimensional (3-D) conformal planning is an essential tool in dose escalation studies to determine the maximum tolerated dose of radiation; (4) biological/radiobiological:metabolic factors. Biologic markers resulting From genetic lesions in lung cancer are grouped as follows: (a) oncogene amplification and overexpression (aberrant gene expression) and mutated tumor suppressor genes - ras gene, myc gene, HER-2/neu and survivin gene, p53 and mutated beta -tubulin gene: (b) tumor biologic/radiobiologic factors tumor cell proliferation kinetics, hypoxia, intrinsic cellular radiosensitivity, gamma factor, and DNA content; (c) enzymes and hormones: neuron-specific enolase, serum lactate dehydrogenase. and enhanced glucose metabolic rate supported by increased glucose transporter protein. The surviving fraction of tumor cells at 2.0 Gy of radiation (SF2) as a measure of intrinsic tumor cell radiosensitivity, potential doubling time (T-Pot) as a measure of the rate of tumor cell proliferation and gamma factor representing the slope of the survival curve at 50% survival rate are being investigated as potential predictors for therapy response. Enhanced glucose utilization, a hallmark of malignant transformation, is being studied as a potential monitor for therapy response by using PET-FDG. Conclusion: Current data indicate that there is a dose-response relationship between radiation dose and local tumor control, and also between local tumor control and survival in stage III NSCLC. Therapeutic factors, i.e. total radiation dose, fractionation schedule and dose intensity, and use of 3-D conformal radiation to secure the optimum therapeutic ratio are important for improved local tumor control and survival. Future research should be directed towards radiation dose escalation using 3-D conformal therapy to determine the maximum tolerated dose (MTD) of radiation in chemo-radiotherapy. and the use of this MTD for improved local tumor control and survival. Radiobiological, molecular, and metabolic markers may have potential for monitoring tumor response and optimizing radiation therapy. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Dresden, Med Fac Carl Gustav Carus, Dresden, Germany. Univ Wurzburg, Wurzburg, Germany. Tampere Univ Hosp, Tampere, Finland. Univ Rotterdam Hosp, Rotterdam, Netherlands. Staedt Kliniken Offenbach, Strahlenklin, Offenbach, Germany. Hygeia Hosp, Dept Med Oncol, Athens, Greece. RP Choi, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. OI Senan, Suresh/0000-0003-3995-2204 NR 86 TC 60 Z9 75 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JAN PY 2001 VL 31 IS 1 BP 43 EP 56 DI 10.1016/S0169-5002(00)00156-2 PG 14 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 386RW UT WOS:000166076200007 PM 11162866 ER PT J AU Vigneron, D Bollen, A McDermott, M Wald, L Day, M Moyher-Noworolski, S Henry, R Chang, S Berger, M Dillon, W Nelson, S AF Vigneron, D Bollen, A McDermott, M Wald, L Day, M Moyher-Noworolski, S Henry, R Chang, S Berger, M Dillon, W Nelson, S TI Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors SO MAGNETIC RESONANCE IMAGING LA English DT Article DE Magnetic Resonance Spectroscopic Imaging; brain tumors; MRSI; cancer ID H-1 MR SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; H-1-NMR SPECTROSCOPY; NMR-SPECTROSCOPY; INTRACRANIAL TUMORS; CEREBRAL GLIOMAS; VOLUME MRI; IN-VITRO; INVIVO; LOCALIZATION AB The goal of this study was to determine whether presurgical metabolite levels measured by 3D MR Spectroscopic Imaging (MRSI) can accurately detect viable cancer within human brain tumor masses. A total of 31 patients (33 exams, 39 pathology correlations) with brain tumors were studied prior to surgical biopsy and/or resection. The 3D MRSI was obtained with a spatial resolution of 0.2 to 1 cc throughout the majority of the mass and adjacent brain tissue using PRESS-CSI localization. Levels of choline, creatine and NAA were estimated from the locations of the resected tissue and normalized to normal appearing brain tissue. The data were correlated with subsequent histologic analysis of the biopsy tissue samples. Although there were large variations in the metabolite ratios, all regions of confirmed cancer demonstrated significant choline levels and a mean choline/NAA ratio of 5.84 + 2.58 with the lowest value being 1.3. This lowest value is greater than 4 standard deviations above the mean (0.52 +/- 0.13) found in 8 normal volunteers. The choline signal intensities in confirmed cancers were significantly elevated compared to normal appearing brain tissue with a mean ratio of 1.71 +/- 0.69. Spectra with no significant metabolite levels were observed in the non-enhancing necrotic core of the tumor masses. The results of this study indicate that 3D MRSI of brain tumors can detect abnormal metabolite levels in regions of viable cancer and grades and can differentiate cancer from necrosis and/or normal brain tissue. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Charlestown, MA 02129 USA. RP Vigneron, D (reprint author), Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RI Wald, Lawrence/D-4151-2009 FU NCI NIH HHS [R01 CA57236] NR 37 TC 64 Z9 67 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JAN PY 2001 VL 19 IS 1 BP 89 EP 101 DI 10.1016/S0730-725X(01)00225-9 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 418QN UT WOS:000167903000012 PM 11295350 ER PT J AU de Crespigny, AJ Rother, R Beaulieu, C Neumann-Haefelin, T Moseley, ME AF de Crespigny, AJ Rother, R Beaulieu, C Neumann-Haefelin, T Moseley, ME TI Comparison of diffusion, blood oxygenation, and blood volume changes during global ischemia in rats SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; cerebral ischemia, global; cerebral blood volume; rats; blood oxygenation ID RESONANCE-IMAGING ASSESSMENT; FOCAL CEREBRAL-ISCHEMIA; REVERSIBLE ISCHEMIA; WATER DIFFUSION; CAT BRAIN; MRI; CONTRAST; ECHO; ADC; HYPERGLYCEMIA AB Rapid diffusion, blood oxygenation, and blood volume weighted echo planar imaging was used to monitor global cerebral ischemia by cardiac arrest in rats. Serial CBV measurements used intravascular iron oxide contrast media (iron dextran), ADC dropped by 5% within 20 sec of cardiac arrest, then continued to decay slowly until a larger rapid drop after 2 min. After iron oxide injection, the initial 5% drop was not observed. The transverse relaxation rate (R-2, R-2* no iron injection) increased rapidly after cardiac arrest, peaking at about 30 sec, then declining towards baseline. The CBV dropped by about 50% within 20 sec. The initial 5% ADC drop may be a vascular artifact. The rapidity of the CBV-weighted signal drop suggests a flow-mediated contribution to the iron oxide contrast mechanism. Magn Reson Med 45:10-16, 2001. (C) 2001 Wiley-Liss, Inc. C1 Stanford Univ, Dept Radiol, Lucas Ctr, Stanford, CA 94305 USA. Univ Hamburg, Neurol Klin, Hamburg, Germany. Univ Alberta, Dept Biomed Engn, Edmonton, AB, Canada. RP de Crespigny, AJ (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Beaulieu, Christian/E-9796-2011 OI Beaulieu, Christian/0000-0002-2342-3298 FU NCRR NIH HHS [1 P41 RR09784-01] NR 33 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2001 VL 45 IS 1 BP 10 EP 16 DI 10.1002/1522-2594(200101)45:1<10::AID-MRM1002>3.0.CO;2-J PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 388FU UT WOS:000166167400002 PM 11146479 ER PT J AU von Boehmer, H Jaeckel, E AF von Boehmer, H Jaeckel, E TI Peripheral tolerance and organ specific autoimmunity SO MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VIII: AUTOIMMUNITY 2000 AND BEYOND SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID T-CELL TOLERANCE; DRIVEN BYSTANDER SUPPRESSION; DEPENDENT DIABETES-MELLITUS; RECEPTOR TRANSGENIC MICE; MYELIN BASIC-PROTEIN; IN-VIVO; VIRUS-INFECTION; SELF-ANTIGENS; CLONAL ELIMINATION; CROSS-PRESENTATION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 59 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 490 BP 41 EP 48 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BS74S UT WOS:000171041500005 PM 11505973 ER PT J AU Ubel, PA Jepson, C Baron, J AF Ubel, PA Jepson, C Baron, J TI The inclusion of patient testimonials in decision aids: Effects on treatment choices SO MEDICAL DECISION MAKING LA English DT Editorial Material DE decision making; cognitive bias; decision aid; informed consent; vividness ID INFORMED CONSENT; INFORMATION; IMPACT AB Background. Decision aids often provide statistical information and patient testimonials to guide treatment choices. This raises the possibility that the testimonials will overwhelm the statistical information. Methods. Prospective jurors in Philadelphia County were presented with hypothetical statistical information about the percentage of angina patents who benefit from angioplasty and bypass surgery (50% and 75%, respectively). They were also given written testimonials from hypothetical patents who had benefited or not benefited from each of the two treatments. The numbers of patients benefiting and not benefiting were varied to be either proportionate to the statistical information or disproportionate. In study 1, all participants received 1 testimonial from a patient who had benefited from angioplasty and 1 from a patient who had not. Participants receiving the proportionate questionnaire version were also given 3 testimonials from patents who benefited from bypass surgery and 1 from a patient who did not, coinciding with the hypothetical statistical information. In contrast, participants receiving the disproportionate questionnaire version received only I testimonial from a patent who benefited from surgery and I from a patient who did not. In study 2, all participants received 2 examples of patients who benefited from angioplasty and 2 who did not. Participants with the proportionate questionnaire version received the same testimonials regarding surgery as in study 1. Those receiving the disproportionate questionnaire version received 2 testimonials from patients who benefited from bypass and 2 from patients who did not. Finally, a separate set of participants in study 2 received a questionnaire with no testimonials. Results. In study 1, 30% of participants receiving the disproportionate questionnaire version chose bypass surgery versus 44% of those receiving the proportionate questionnaire (P = 0.002 by chi (2)). In study 2, 34% of participants receiving the disproportionate questionnaire version chose bypass surgery versus 37% of those receiving the proportionate questionnaire (P = 0.59 by chi (2)). Of those receiving no patent testimonials, 58% chose bypass surgery. Conclusions. The inclusion of written patient testimonials significantly influenced hypothetical treatment choices. Efforts to make the mix of positive versus negative testimonials proportionate to statistical information may, under some circumstances, affect choices in ways that cannot automatically be assumed to be optimal. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. RP Ubel, PA (reprint author), Univ Michigan, Div Gen Internal Med, 300 N Ingalls,Room 7B20, Ann Arbor, MI 48109 USA. NR 17 TC 79 Z9 79 U1 1 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2001 VL 21 IS 1 BP 60 EP 68 PG 9 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 469EL UT WOS:000170801600008 PM 11206948 ER PT J AU Jiang, SB Boyer, AL Ma, CMC AF Jiang, SB Boyer, AL Ma, CMC TI Modeling the extrafocal radiation and monitor chamber backscatter for photon beam dose calculation SO MEDICAL PHYSICS LA English DT Article DE photon beam; extrafocal radiation; monitor chamber backscatter; dose calculation; in-air output factor ID HEAD-SCATTER FACTORS; X-RAY-BEAMS; OUTPUT FACTORS; MULTILEAF COLLIMATORS; LINEAR ACCELERATORS; FLATTENING-FILTER; THERAPY BEAMS; FIELDS AB A simple analytical approach has been developed to model extrafocal radiation and monitor chamber backscatter for clinical photon beams. Model parameters for both the extrafocal source and monitor chamber backscatter are determined simultaneously using conventional measured data, i.e., in-air output factors for square and rectangular fields defined by the photon jaws. The model has been applied to 6 MV and 15 MV photon beams produced by a Varian Clinac 2300C/D accelerator. Contributions to the in-air output factor from the extrafocal radiation and monitor chamber backscatter, as predicted by the model, are in good agreement with the measurements. The model can be used to calculate the in-air output factors analytically, with an accuracy of 0.2% for symmetric or asymmetric rectangular fields defined by jaws when the calculation point is at the isocenter and 0.5% when the calculation point is at an extended SSD. For MLC-defined fields, with the jaws at the recommended positions, calculated in-air output factors agree with the measured data to within 0.3% at the isocenter and 0.7% at off-axis positions. The model has been incorporated into a Monte Carlo dose algorithm to calculate the absolute dose distributions in patients or phantoms. For three MLC-defined irregular fields (triangle shape, C-shape, and L-shape), the calculations agree with the measurements to about 1% even for points at off-axis positions. The model will be particularly useful for IMRT dose calculations because it accurately predicts beam output and penumbra dose. (C) 2001 American Association of Physicists in Medicine. C1 Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. RP Jiang, SB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA78331, CA43840] NR 36 TC 47 Z9 48 U1 0 U2 13 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2001 VL 28 IS 1 BP 55 EP 66 DI 10.1118/1.1333747 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 398NJ UT WOS:000166762300009 PM 11213923 ER PT J AU Song, MK Rosenthal, MJ Hong, SJ Harris, DM Hwang, I Yip, I Golub, MS Ament, ME Go, VLW AF Song, MK Rosenthal, MJ Hong, SJ Harris, DM Hwang, I Yip, I Golub, MS Ament, ME Go, VLW TI Synergistic antidiabetic activities of zinc, cycle (his-pro), and arachidonic acid SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DEPENDENT DIABETES-MELLITUS; INSULIN-RECEPTOR KINASE; HUMAN SKELETAL-MUSCLE; PANCREATIC-ISLETS; GLUCOSE-TOLERANCE; ZUCKER RATS; HORMONE; THYROTROPIN; PLASMA; DEFICIENCY AB Previous studies have already shown that prostate extract (PE) has antidiabetic activity when given to animals and humans. In this study, we explore whether this antidiabetic activity is related to the high concentrations of zinc, cycle this-pro) (CHP), and the prostaglandin precursor, arachidonic acid (AA), in prostate tissue. When streptozotocin-induced diabetic rats were given drinking water containing 10 mg/L zinc and 100 mg/L PE for 3 weeks, fasting blood glucose levels and glucose clearance rates, but not plasma insulin levels, were significantly lower than at pretreatment. In subsequent experiments, blood glucose levels in rats given PE for 3 weeks were significantly lower than in rats given distilled water or 10 mg/L zinc alone. However, in rats given 100 mg/L CHP with zinc, blood glucose levels were also lower than in rats given PE atone. Time-course studies in diabetic rats given drinking water containing 20 mg/L Zn, 20 mg/L L-histidine, and 10 mg/L CHP showed that blood glucose levels dropped 209 +/- 53 mg/dL in 1 day and stayed low for 2 weeks. When CHP was replaced with 100 mg AA/L, blood glucose levels dropped 230 +/- 64 mg/dL in 5 days, but returned to the original values 11 days later. Growth rate improved and water consumption decreased significantly in CHP- and AA-treated diabetic rats. High intake of L-histidine and testosterone increased blood glucose concentrations in diabetic rats. To determine optimal dosages of CHP and AA, we gave rats drinking water containing 10 mg/L Zn and 0.5 mg/L L-histidine with various concentrations of CHP or AA. The most effective doses for reducing blood glucose levels were 0.32 mg CHP/kg/day and 11 mg AA/kg/day. These data suggest that the active antidiabetic ingredients in the PE are CHP, zinc, and AA or its precursors. Copyright (C) 2001 by W.B. Saunders Company. C1 Univ Calif Los Angeles, Ctr Human Nutr, Dept Med, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Go, VLW (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, Dept Med, Sch Med, Room 12-217 Warren Hall,900 Veteran Ave,Box 17862, Los Angeles, CA 90095 USA. FU NIDDK NIH HHS [1 R43 DK56546-01] NR 56 TC 33 Z9 36 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2001 VL 50 IS 1 BP 53 EP 59 DI 10.1053/meta.2001.19427 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 391HL UT WOS:000166350500010 PM 11172475 ER PT J AU Klein, RL Ascencao, JL Mironova, M Huang, Y Lopes-Virella, MF AF Klein, RL Ascencao, JL Mironova, M Huang, Y Lopes-Virella, MF TI Effect of inflammatory cytokines on the metabolism of low-density lipoproteins by human vascular endothelial cells SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; TUMOR-NECROSIS-FACTOR; CONTAINING IMMUNE-COMPLEXES; CORONARY-ARTERY DISEASE; OXIDIZED LDL; ADHESION MOLECULE-1; DIABETES-MELLITUS; GENE-EXPRESSION; HEPG2 CELLS; RECEPTOR AB Cytokines have been shown to activate multiple, varied metabolic pathways in endothelial cells. Little information is available concerning the effects of inflammatory cytokines on lipoprotein metabolism by vascular endothelial cells. Human umbilical vein endothelial cells (HuECs) and bovine aortic endothelial cells (BAECs) were incubated with the inflammatory cytokines recombinant human interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF), interferon gamma (gamma -IF), and interferon beta (beta -IF) at increasing concentrations (0.1 to 1,000 U/mL), for increasing periods (6 to 72 hours), After the incubation period, the media were removed and replaced with serum-free media containing radiolabeled native or acetylated low-density lipoprotein (Ac-LDL) and the rates of degradation and accumulation of radiolabeled LDL were determined. The degradation and accumulation of I-125-LDL were significantly increased (P < .02) in HuECs preincubated with IL-1 (100 U/mL) compared with control incubations without the cytokine or incubations containing -IF, beta -IF, or TNF. This resulted from a 38% increase in LDL receptor protein in cells incubated with IL-1. The increased rate of LDL catabolism by HuECs incubated with IL-l was accompanied by a significant increase (P < .05) in the rate of cholesteryl ester synthesis in the cells. Cholesteryl ester synthesis rates in HuECs preincubated with -IF, beta -IF, or TNF did not differ significantly from the rates in control incubations. The effect of preincubation with cytokine on the activity of the scavenger receptor was also determined. There were no significant differences in the rate of degradation or accumulation of radiolabeled Ac-LDL in control incubations compared with cultures preincubated with IL-1, gamma -IF, beta -IF, or TNF. There also were no significant differences in the rate of catabolism of native LDL or Ac-LDL in BAECs preincubated with cytokines. Although cytokines have been shown previously to alter the binding of monocytes to endothelial cells, there was no significant increase in the binding of monocytes to cultures incubated with IL-1 plus LDL compared with IL-1 alone, In summary, we now demonstrate that cytokines, specifically IL-1, may alter LDL metabolism by human vascular endothelial cells and alter endothelial cell cholesterol metabolism. These changes in endothelial cell metabolism provide additional evidence supporting the critical role of cytokines in atherogenesis. Copyright (C) 2001 by W.B. Saunders Company. C1 Ralph H Johnson Dept Vet Affairs Med Ctr, Res Serv 151, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Reno, NV USA. Univ Nevada, Sch Med, Reno, NV 89557 USA. RP Klein, RL (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. NR 31 TC 8 Z9 13 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2001 VL 50 IS 1 BP 99 EP 106 DI 10.1053/meta.2001.19446 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 391HL UT WOS:000166350500017 PM 11172482 ER PT J AU Stamenkovic, I AF Stamenkovic, I TI Analysis of reactive oxygen species in cell death SO METHODS IN CELL BIOLOGY, VOL 66 SE METHODS IN CELL BIOLOGY LA English DT Review ID NADH OXIDASE; NITRIC-OXIDE; CYTOCHROME-C; APOPTOSIS; PROTEASE; INHIBITION; ACTIVATION; GROWTH; INDUCTION; PROTEINS C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Stamenkovic, I (reprint author), Harvard Univ, Sch Med, Dept Pathol, Charlestown Navy Yard, Boston, MA 02129 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2001 VL 66 BP 307 EP 319 PG 13 WC Cell Biology SC Cell Biology GA BS42U UT WOS:000169819400013 PM 11396009 ER PT S AU White, K Lisi, S Kurada, P Franc, N Bangs, P AF White, K Lisi, S Kurada, P Franc, N Bangs, P BE Schwartz, LM Ashwell, JD TI Methods for studying apoptosis and phagocytosis of apoptotic cells in Drosophila tissues and cell lines SO METHODS IN CELL BIOLOGY, VOL 66: APOPTOSIS SE Methods in Cell Biology LA English DT Review ID GENETIC-CONTROL; DEATH; PROTEIN; SURVIVAL; RECEPTOR; REAPER; EYE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI Franc, Nathalie/C-2208-2009; White, Kristin/D-7936-2013 NR 21 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 0-12-632447-6; 0-12-544165-7 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2001 VL 66 BP 321 EP + PG 22 WC Cell Biology SC Cell Biology GA BS42U UT WOS:000169819400014 PM 11396010 ER PT J AU Hadlock, TA Sundback, CA Hunter, DA Vacanti, JP Cheney, ML AF Hadlock, TA Sundback, CA Hunter, DA Vacanti, JP Cheney, ML TI A new artificial nerve graft containing rolled Schwann cell monolayers SO MICROSURGERY LA English DT Article; Proceedings Paper CT Spring Meeting of the Triologic Section of the Combined Otolaryngology CY MAY 18, 2000 CL ORLANDO, FLORIDA ID PERIPHERAL-NERVE; REGENERATION; REPAIR AB This study hypothesized that introducing high numbers of Schwann cells in monolayers via a novel rolled graft architecture would promote robust nerve regeneration. The objective was to place adherent Schwann cells in artificial nerve grafts and to assess regeneration through the Schwann cell-laden grafts compared with that through acellular grafts and autografts, Schwann cells were isolated from neonatal Fisher rats. Small intestinal submucosa (SIS) was harvested from adult Fisher rats, cut into 7 mm x 8 cm pieces, and pinned out, Schwann cells were plated onto the strips, allowed to reach confluence, and subsequently rolled into a laminar structure and implanted across a 7-mm gap in the rat sciatic nerve (n = 12). Control animals received SIS conduits without Schwann cells (n = 11) or autograft repair (n = 12), At 10.5 weeks, functional regeneration through the Schwann cell-laden grafts, measured by both sciatic function index and extensor postural thrust testing, exceeded that through the cell-free grafts and approached that achieved through autografts. These results highlight the role of Schwann cells in nerve regeneration. Regenerative results approaching autograft levels in the Schwann cell-laden group suggest that this methodology may ultimately be useful in clinical nerve repair. (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 22 TC 54 Z9 79 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0738-1085 J9 MICROSURG JI Microsurgery PY 2001 VL 21 IS 3 BP 96 EP 101 DI 10.1002/micr.1016 PG 6 WC Surgery SC Surgery GA 439MJ UT WOS:000169120400004 PM 11372069 ER PT J AU Granter, SR Weilbaecher, KN Quigley, C Fletcher, CDM Fisher, DE AF Granter, SR Weilbaecher, KN Quigley, C Fletcher, CDM Fisher, DE TI Clear cell sarcoma shows immunoreactivity for microphthalmia transcription factor: Further evidence for melanocytic differentiation SO MODERN PATHOLOGY LA English DT Article DE clear cell sarcoma; D5 immunoreactivity; microphthalmia transcription factor; melanoma ID MALIGNANT-MELANOMA; SOFT PARTS; CHROMOSOMAL-ABNORMALITIES; APONEUROSES; TENDONS AB Microphthalmia transcription factor, a melanocytic nuclear protein critical for the embryonic development and postnatal viability of melanocytes, is a master regulator in modulating extracellular signals. Recently, microphthalmia transcription factor expression was shown to be both a sensitive and specific marker of epithelioid melanoma. We investigated the sensitivity of D5, an anti-microphthalmia transcription factor antibody, for diagnosis of clear cell sarcoma (also known as malignant melanoma of soft parts). Immunoreactivity in a nuclear pattern for D5 was present in 8 of 12 (75%) tumors. D5 staining was strong fn three tumors, moderate in two, and weak in three. S-100 protein expression was seen in all 12 cases that had clear cell sarcoma examined. HMB-45 staining was seen in 11 of 12 (92%) tumors. Focal Melan-A positivity was seen in 3 of 7 (43%) tumors. Although D5 was shown in a previous study to be a highly sensitive and specific marker for epithelioid melanomas, the results of this study expand the spectrum of tumors showing immunoreactivity for D5. D5 immunoreactivity in clear cell sarcoma provides further evidence for melanocytic differentiation in this unusual tumor. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Granter, SR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 13 TC 42 Z9 44 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 BP 6 EP 9 DI 10.1038/modpathol.3880249 PG 4 WC Pathology SC Pathology GA 396EB UT WOS:000166622400002 PM 11211309 ER PT J AU Kesavan, S Rosenberg, AS Selig, MK Nielsen, GP AF Kesavan, S Rosenberg, AS Selig, MK Nielsen, GP TI The reclassification of MFH as fibrosarcoma: A proposal based on the analysis of the ultrastructural features of 100 cases. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Singapore Gen Hosp, Dept Pathol, Singapore, Singapore. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 59 BP 14A EP 14A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400067 ER PT J AU Nielsen, GP Fletcher, CDM Smith, M Rosenberg, AE AF Nielsen, GP Fletcher, CDM Smith, M Rosenberg, AE TI Soft tissue aneurysmal bone cyst. A clinicopathological study of 5 cases. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. St Thomas Hosp, Dept Orthoped, London SE1 7EH, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 73 BP 16A EP 16A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400081 ER PT J AU O'Connell, JX Nielsen, GP Ishida, T Kahn, L Fugunaga, M Rosenberg, AE AF O'Connell, JX Nielsen, GP Ishida, T Kahn, L Fugunaga, M Rosenberg, AE TI Insular and trabecular round cell sarcoma. A proposal for the recognition of a distinct bone neoplasm. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Surrey Mem Hosp, Surrey, BC, Canada. Tokyo Univ Hosp, Tokyo 113, Japan. Jikei Univ, Sch Med, Tokyo, Japan. Long Isl Jewish Med Ctr, New Hyde Park, NY 11042 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 75 BP 16A EP 16A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400083 ER PT J AU Rosenberg, AE Fletcher, CDM Nielsen, GP AF Rosenberg, AE Fletcher, CDM Nielsen, GP TI Intra-articular sarcomas: A study of 9 cases. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 86 BP 18A EP 18A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400094 ER PT J AU Nasser, SM Polyak, K AF Nasser, SM Polyak, K TI Frequent allelic loss on chromosome 17q24-q25 in Ductal carcinoma in situ (DCIS) of the breast. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 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 NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 172 BP 32A EP 32A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400180 ER PT J AU Signoretti, S Monti, F Isaac, B Waltregny, D Dilks, J Gelman, R Pagano, M Loda, M AF Signoretti, S Monti, F Isaac, B Waltregny, D Dilks, J Gelman, R Pagano, M Loda, M TI The p27 ubiquitin ligase Skp2 is overexpressed in breast cancer. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 197 BP 37A EP 37A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400205 ER PT J AU Brogi, E Tambouret, R Bell, DA AF Brogi, E Tambouret, R Bell, DA TI Classification of benign endometrial cells in cervical smears from postmenopausal women on hormone replacement therapy SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 272 BP 49A EP 49A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400280 ER PT J AU Elliott, DD Krane, JF Pitman, MB Pilch, BZ Faquin, WC AF Elliott, DD Krane, JF Pitman, MB Pilch, BZ Faquin, WC TI Fine needle aspiration biopsy (FNAB) of salivary gland basal cell tumors. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 284 BP 51A EP 51A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400292 ER PT J AU McKee, GT Mosher, R AF McKee, GT Mosher, R TI The significance of atypia in breast cyst fluid SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Faulkner Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 318 BP 57A EP 57A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400326 ER PT J AU Mohammadkhani, M Cooper, TL AF Mohammadkhani, M Cooper, TL TI Marginal zone lymphoma(MZL): A potential cause of false negative fine needle aspiration (FNA) diagnosis. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 324 BP 58A EP 58A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400332 ER PT J AU Mohammadkhani, M McKee, GT AF Mohammadkhani, M McKee, GT TI A potential pitfall in fine-needle aspiration (FNA) of axillary lymph node SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 323 BP 58A EP 58A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400331 ER PT J AU Nasser, SM Pitman, MB Pilch, BZ Glyptis, T Faquin, WC AF Nasser, SM Pitman, MB Pilch, BZ Glyptis, T Faquin, WC TI DNA topoisomerase II alpha expression in thyroid fine needle aspiration biopsies of benign and malignant follicular neoplasms. SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 326 BP 58A EP 58A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400334 ER PT J AU Wieczorek, TJ Faquin, WC Rubin, BP Cibas, ES AF Wieczorek, TJ Faquin, WC Rubin, BP Cibas, ES TI Cytologic diagnosis of gastrointestinal stromal tumor (GIST) with emphasis on the differential diagnosis with leiomyosarcoma (LMS) SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 363 BP 64A EP 64A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400371 ER PT J AU Wieczorek, TJ Krane, JF Domanski, HA Akerman, M Carlen, B Misdraji, J Granter, SR AF Wieczorek, TJ Krane, JF Domanski, HA Akerman, M Carlen, B Misdraji, J Granter, SR TI Cytologic findings in granular cell tumors, with emphasis on the diagnosis of malignant granular cell tumor by FNA SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Lund Hosp, S-22185 Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 362 BP 64A EP 64A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400370 ER PT J AU Busam, KJ Hester, K Sachs, D Ho, S Charles, C Zavislan, J Gonzalez, S Halpern, AC AF Busam, KJ Hester, K Sachs, D Ho, S Charles, C Zavislan, J Gonzalez, S Halpern, AC TI Detection of amelanotic cutaneous melanoma and evaluation of its margins by in vivo confocal scanning laser microscopy (CSLM) SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2001 VL 14 IS 1 MA 371 BP 66A EP 66A PG 1 WC Pathology SC Pathology GA 396EB UT WOS:000166622400379 ER EF