FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Schaefer, PW AF Schaefer, PW TI Applications of DWI in clinical neurology SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 4th Advanced Course on Magnetic Resonance Techniques in Multiple Sclerosis CY MAY 18-20, 2000 CL MILIAN, ITALY DE EP DWI; magnetic resonance; neurologic deficit ID DIFFUSION-WEIGHTED MR; CREUTZFELDT-JAKOB-DISEASE; ACUTE CEREBRAL-ISCHEMIA; HIGH-RESOLUTION MEASUREMENT; TRAUMATIC BRAIN INJURY; TRACER BOLUS PASSAGES; MAGNETIC-RESONANCE; ACUTE STROKE; APPARENT DIFFUSION; SIGNAL INTENSITY AB Echo planar diffusion-weighted imaging (EP DWI) provides information about the physiologic state of the brain that is not available on conventional magnetic resonance (MR) images. Specifically, it provides signal proportional to the molecular diffusion of water molecules. It has proven highly sensitive in the detection of acute infarction and it is reliable in differentiating acute stroke from other diseases that mimic acute stroke clinically and on conventional MR images. With perfusion imaging, diffusion-weighted imaging is useful in predicting final infarct size and patient outcome. Diffusion MR is also becoming increasingly useful in the evaluation of a wide variety of other disease processes including neoplasms, intracranial infections and traumatic brain injury. Because acute stroke is common in the differential diagnosis of the majority of patients who present with acute neurologic deficits, diffusion-weighted imaging has become an essential sequence. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Neuroradiol, Boston, MA 02115 USA. RP Schaefer, PW (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, Fruit St,GRB 285, Boston, MA 02114 USA. NR 92 TC 33 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAY 1 PY 2001 VL 186 SU 1 BP S25 EP S35 DI 10.1016/S0022-510X(01)00488-9 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 450FJ UT WOS:000169730600005 PM 11334987 ER PT J AU Januzzi, JL Chae, CU Sabatine, MS Jang, IK AF Januzzi, JL Chae, CU Sabatine, MS Jang, IK TI Elevation in serum troponin I predicts the benefit of tirofiban SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE acute coronary syndromes; glycoprotein IIb/IIIa inhibitor; troponins ID ACUTE CORONARY SYNDROMES; REFRACTORY UNSTABLE ANGINA; WAVE MYOCARDIAL-INFARCTION; INTRACORONARY THROMBUS; PRISM-PLUS; T LEVELS; RISK; STRATIFICATION; DEATH AB Background: Elevations in serum troponins among patients with acute coronary syndromes have been shown to identify those patients who are at high risk for poor outcome and who accrue larger relative benefits from aggressive antiplatelet and antithrombotic therapies. We studied a group of patients from the PRISM-PLUS trial to explore whether simply using serum troponin I, a serum marker of cardiac injury, could predict benefit of GP IIb/IIIa receptor antagonism with tirofiban. Methods and Results: For this study, the subjects consisted of 55 patients receiving the combination therapy of tirofiban/heparin, and 55 receiving heparin alone. The baseline characteristics were similar between the two treatment groups. Serial blood samples were obtained over the first 24-hour period following randomization to study drug, and were analyzed for troponin I (TnI) levels. Among those patients with elevated serum TnI (>0.5 ng/ml), the 30-day event rate for death or myocardial infarction (MI) was reduced from 20.6% among the heparin only group to 3.6% for those treated with the combination of tirofiban/heparin, an absolute risk reduction of 17% and relative risk reduction of 83% (p=0.06). Among the TnI negative patients, the rates of death/MI at 30 days were 9.5% and 11.1% among the combination and heparin treated groups respectively (p=NS). Conclusion: Irrespective of high-risk clinical factors, including ST segment depression, these data support the hypothesis that serum troponins identify those who benefit from aggressive antiplatelet therapy with tirofiban. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 21 Z9 24 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD MAY PY 2001 VL 11 IS 3 BP 211 EP 215 DI 10.1023/A:1011956703031 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 477QL UT WOS:000171295700004 PM 11577259 ER PT J AU Choo, JK Kereiakes, DJ AF Choo, JK Kereiakes, DJ TI Low molecular weight heparin therapy for percutaneous coronary intervention: A practice in evolution SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE anticoagulation; coronary intervention; low molecular weight heparin ID UNFRACTIONATED HEPARIN; MYOCARDIAL-INFARCTION; ARTERY DISEASE; ANGIOPLASTY; ENOXAPARIN; TRIAL; THROMBOLYSIS; CLOSURE; TIME AB Unfractionated heparin (UFH) remains the principal antithrombotic agent during percutaneous coronary intervention (PCI) but is associated with significant limitations including an unpredictable anticoagulation dose response, the requirement for frequent monitoring, and transient rebound hypercoagulability. Low molecular weight heparin (LMWH) represents an attractive alternative due to its predictable dose response relationship, superior antithrombotic efficacy and potential for improved clinical safety, and has been used increasingly in patients with acute coronary syndromes prior to coronary angiography. The rationale and existing data regarding the use of LMWH in PCI is summarized and reviewed. Preliminary clinical guidelines for the use of LMWH in the transition from medical stabilization of patients with acute coronary syndromes to invasive management in the catheterization laboratory are presented. C1 Carl & Edyth Lindner Ctr Res & Educ, Cincinnati, OH 45219 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Ohio Heart Hlth Ctr, Cincinnati, OH USA. RP Kereiakes, DJ (reprint author), Carl & Edyth Lindner Ctr Res & Educ, 2123 Auburn Ave,Suite 424, Cincinnati, OH 45219 USA. NR 29 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD MAY PY 2001 VL 11 IS 3 BP 235 EP 246 DI 10.1023/A:1011917021686 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 477QL UT WOS:000171295700008 PM 11577263 ER PT J AU Dretler, SP AF Dretler, SP TI The stone cone: A new generation of basketry SO JOURNAL OF UROLOGY LA English DT Article DE ureter; pilot projects; lithotripsy; equipment and supplies; calculi ID URETEROSCOPY; LITHOTRIPSY AB Purpose: We designed a device to minimize ureteral stone migration during intracorporeal lithotripsy, decrease the likelihood of stone and/or basket entrapment, and extract whale stones and fragments. Materials and Methods: Nitinol and stainless steel wires were configured into expandable tapered cones, which were placed cephalad to in vitro and in vitro concretions, and used to trap and extract stones as well as other test material. Safety features were evaluated by measuring the release of ball bearings and the tension needed to unwind the coils of the cone, which were greater than 4 mm. in diameter. We treated 4 patients with ureteral calculi using the Stone Cone dagger to prevent migration and extract fragments. Results: The cone-shaped devices expanded to occlude the test devices and human ureters, and prevented stone migration. They extracted whole concretions and fragments greater than 1.5 mm. The cone-shaped basket released a 5.5 mm, ball bearing at an average 0.127 pounds of tension when pulled through a 6 mm. plastic orifice. Coils greater than 4 mm. in diameter were straightened at a tension of 0.10 to 0.14 pounds. Stone migration during intracorporeal lithotripsy was prevented in the 4 patients with ureteral calculi, in whom large and small fragments were safely extracted. Conclusions: The Stone Cone may be placed via a ureteral catheter and opened cephalad to a ureteral stone to prevent stone migration during intracorporeal lithotripsy. It may extract whole stones and fragments greater than 1.5 mm. It is designed, so that its coils greater than 4 mm. in diameter release concretions too wide for the ureter or ureteral orifice after approximately 0.127 pounds of tension are applied. Because of these features, the Stone Cone represents a new generation of basketry appropriate to the era of ureteroscopy and intracorporeal lithotripsy. It is worthy of further clinical study. C1 Massachusetts Gen Hosp, Kidney Stone Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. RP Dretler, SP (reprint author), Massachusetts Gen Hosp, Kidney Stone Ctr, Boston, MA 02114 USA. NR 13 TC 50 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2001 VL 165 IS 5 BP 1593 EP 1596 DI 10.1016/S0022-5347(05)66355-0 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 426CP UT WOS:000168321500055 PM 11342924 ER PT J AU Cromie, WJ Lee, K Houde, K Holmes, L AF Cromie, WJ Lee, K Houde, K Holmes, L TI Implications of prenatal ultrasound screening in the incidence of major genitourinary malformations SO JOURNAL OF UROLOGY LA English DT Article DE ultrasonography, prenatal; urogenital system; pediatrics ID PREVALENCE; IMPACT AB Purpose: During the last 3 decades infant mortality has decreased nearly 50%. While neonatal intensive care deserves much of the credit, the recent increase in prenatal ultrasound from 33% of pregnancies in 1950 to 78% in 1987 has improved early detection. We evaluate the impact of prenatal ultrasound on major genitourinary malformations. Materials and Methods: Data obtained from the Malformations Surveillance Program at Brigham and Women's Hospital between 1974 and 1994 tracked 163,431 pregnancies and termination rates of fetuses with spina bifida, bladder exstrophy, the prune belly syndrome and posterior urethral valves. Results: Hospital data revealed that pregnancy was electively terminated due to spina bifida in 65% of cases, posterior urethral valves in 46%, the prune belly syndrome in 31% and exstrophy in 25%. Conclusions: Clearly, surveillance programs and improved accuracy of prenatal ultrasound have allowed early diagnosis of major genitourinary malformations. Many factors influence decision making in these affected fetal cases, including the financial and emotional impact of these major anomalies during lifetime. Future societal decisions and reduction in these anomalies may influence our training programs: manpower needs, medical facility requirements and character of our practices. These findings may have significant implications in the field of pediatric urology. C1 Univ Chicago, Dept Surg, Urol Sect, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Sect Neonatol, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Teratol Unit, Boston, MA USA. RP Cromie, WJ (reprint author), Univ Chicago, Dept Surg, Urol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. NR 12 TC 25 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2001 VL 165 IS 5 BP 1677 EP 1680 DI 10.1016/S0022-5347(05)66391-4 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 426CP UT WOS:000168321500094 PM 11342955 ER PT J AU Si, ZH Cayabyab, M Sodroski, J AF Si, ZH Cayabyab, M Sodroski, J TI Envelope glycoprotein determinants of neutralization resistance in a simian-human immunodeficiency virus (SHIV-HXBc2P 3.2) derived by passage in monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; T-LYMPHOTROPIC RETROVIRUS; AMINO-ACID SUBSTITUTIONS; RECOMBINANT SOLUBLE CD4; N-LINKED GLYCOSYLATION; PIG-TAILED MACAQUES; AIDS-LIKE DISEASE; IN-VIVO; TRANSMEMBRANE PROTEIN; PERSISTENT INFECTION AB The simian-human immunodeficieny virus SHIV-HXBc2 contains the envelope glycoproteins of a laboratory-adapted, neutralization-sensitive human immunodeficiency virus type 1 variant, HXBc2. Serial in vivo passage of the nonpathogenic SHIV7-HXBc2 generated SHIV KU-1, which causes rapid CD4(+) T-cell depletion and an AIDS-Iike illness in monkeys, A molecularly cloned pathogenic SHIV, SHIV-HXBc2P 3.2? was derived from the SHIV KU-1 isolate and differs from the parental SHIV-HXBc2 by only 12 envelope glycoprotein amino acid residues. Relative to SHIV-HXBc2, SHIV-HXBc2P 3.2 was resistant to neutralization by all of the antibodies tested with the exception of the 2G12 antibody. The sequence changes responsible for neutralization resistance were located in variable regions of the gp120 exterior envelope glycoprotein and in the gp-ll transmembrane envelope glycoprotein. The 2G12 antibody, which neutralized SHIV-HXBc2 and SHIV-HXBc2P 3.2 equally, bound the HXBc2 and HXBc2P 3,2 envelope glycoproteins on the cell surface comparably. The ability of the other tested antibodies to achieve saturation was less for the HXBc2P 3.2 envelope glycoproteins than for the HXBc2 envelope glycoproteins. even though the affinity of the antibodies for the two envelope glycoproteins was similar, Thus, a highly neutralization sensitive SHIV, by modifying both gp120 and gp41 glycoproteins, apparently achieves a neutralization-resistant state by decreasing the saturability of its envelope glycoproteins by antibodies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI24755, AI28691, AI39420, P30 AI028691, R01 AI039420, R37 AI024755] NR 89 TC 46 Z9 47 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 MAY PY 2001 VL 75 IS 9 BP 4208 EP 4218 DI 10.1128/JVI.75.9.4208-4218.2001 PG 11 WC Virology SC Virology GA 421PN UT WOS:000168072900020 PM 11287570 ER PT J AU Islam, SA Hay, CM Hartman, KE He, SQ Shea, AK Trocha, AK Dynan, MJ Reshamwala, N Buchbinder, SP Basgoz, NO Kalams, SA AF Islam, SA Hay, CM Hartman, KE He, SQ Shea, AK Trocha, AK Dynan, MJ Reshamwala, N Buchbinder, SP Basgoz, NO Kalams, SA TI Persistence of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte clones in a subject with rapid disease progression SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; LONGITUDINAL ANALYSIS; RESPONSES; CELLS; VIREMIA; USAGE; ASSOCIATION; SPECIFICITY; EXHAUSTION; ACTIVATION AB We longitudinally measured T-cell receptor transcript frequencies of human immunodeficiency virus type 1 (HIV-1) specific cytotoxic T lymphocytes (CTL) in an individual with rapidly progressive disease and high levels of viremia. CTL clones elicited during acute HIV-1 infection were present at the time of death, despite absent functional CTL responses, arguing against clonal deletion as a mechanism for the decline of CTL responses observed during HIV-1 infection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr & ID Div, Boston, MA 02114 USA. Columbia Univ, New York Presbyterian Hosp, Coll Phys & Surg, New York, NY 10032 USA. Dept Publ Hlth, AIDS Off, San Francisco, CA 94140 USA. RP Kalams, SA (reprint author), Massachusetts Gen Hosp East, CNY 5212,149 13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [R01 AI039966, R01 AI028568, AI-39966, R37 AI028568, AI--28568] NR 23 TC 27 Z9 27 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 MAY PY 2001 VL 75 IS 10 BP 4907 EP 4911 DI 10.1128/JVI.75.10.4907-4911.2001 PG 5 WC Virology SC Virology GA 425UD UT WOS:000168309300047 PM 11312363 ER PT J AU Cohen, LS AF Cohen, LS TI First line therapies for clinical depression SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD MAY PY 2001 VL 10 IS 4 BP 394 EP 394 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 441JY UT WOS:000169228300034 ER PT J AU Gomez, GMA Taylor, AE AF Gomez, GMA Taylor, AE TI Cross-sectional study comparing weight gain and androgen levels in women with epilepsy taking lamotrigine vs valproate monotherapy SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Meeting Abstract C1 Glazo SmithKline, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD MAY PY 2001 VL 10 IS 4 BP 407 EP 407 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 441JY UT WOS:000169228300081 ER PT J AU Pui, CH Sailan, S Relling, MV Masera, G Evans, WE AF Pui, CH Sailan, S Relling, MV Masera, G Evans, WE TI International childhood Acute Lymphoblastic Leukemia workshop: Sausalito, CA, 30 November-1 December 2000 SO LEUKEMIA LA English DT Review DE clinical trials; risk factors; glucocorticoids; Philadelphia chromosome; minimal residual disease; new agents ID MINIMAL RESIDUAL DISEASE; CHILDRENS CANCER GROUP; CAMPATH-1H MONOCLONAL-ANTIBODY; TYROSINE KINASE INHIBITOR; ACUTE MYELOID-LEUKEMIA; PHASE-II MULTICENTER; CLINICAL-SIGNIFICANCE; CRANIAL RADIOTHERAPY; INDUCED CYTOTOXICITY; IN-VITRO C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Tennessee, Coll Med, Memphis, TN USA. Univ Tennessee, Coll Pharm, Memphis, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Univ Milan, Osped San Gerardo, Dept Pediat, Monza, Italy. RP Pui, CH (reprint author), St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. FU NCI NIH HHS [CA78224, CA36401, CA21765, CA51001, CA60419]; NIGMS NIH HHS [U01GM61374, GM61393] NR 89 TC 31 Z9 36 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2001 VL 15 IS 5 BP 707 EP 715 DI 10.1038/sj.leu.2402111 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 436RU UT WOS:000168950000002 PM 11368430 ER PT J AU Yoshiura, T Wu, O Zaheer, A Reese, TG Sorensen, AG AF Yoshiura, T Wu, O Zaheer, A Reese, TG Sorensen, AG TI Highly diffusion-sensitized MRI of brain: Dissociation of gray and white matter SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE human brain; diffusion; DWI; gray and white matter; fractional anisotropy; nonmonoexponential decay ID WATER DIFFUSION; RESTRICTED DIFFUSION; CEREBRAL-ISCHEMIA; NERVOUS-SYSTEM; STROKE; ATTENUATION; ANISOTROPY; TISSUE AB The brains of six healthy volunteers were scanned with a full tenser diffusion MRI technique to study the effect of a high b value on diffusion-weighted images (DWls). The b values ranged from 500 to 5000 s/mm(2). Isotropic DWls, trace apparent diffusion coefficient (ADC) maps, and fractional anisotropy (FA) maps were created for each b value. As the b value increased, ADC decreased in both the gray and white matter. Furthermore, ADC of the white matter became lower than that of the gray matter, and, as a result, the white matter became brighter than the gray matter in the isotropic DWls. Quantitative analysis showed that these changes were due to nonmonoexponential diffusion signal decay of the brain tissue, which was more prominent in white matter than in gray matter. There was no significant change in relation to the b value in the FA maps. High b value appears to have a dissociating effect on gray and white matter in DWls, (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02119 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Boston, MA 02119 USA. RP Sorensen, AG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, CNY 149-2301, Boston, MA 02119 USA. FU NCRR NIH HHS [5P41-RR14075]; NINDS NIH HHS [R01 NS38477-01] NR 19 TC 68 Z9 75 U1 0 U2 1 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 MAY PY 2001 VL 45 IS 5 BP 734 EP 740 DI 10.1002/mrm.1100 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 428CR UT WOS:000168444000002 PM 11323798 ER PT J AU Kominski, G Andersen, R Bastani, R Gould, R Hackman, C Huang, D Jarvik, L Maxwell, A Moye, J Olsen, E Rohrbaugh, R Rosansky, J Taylor, S Van Stone, W AF Kominski, G Andersen, R Bastani, R Gould, R Hackman, C Huang, D Jarvik, L Maxwell, A Moye, J Olsen, E Rohrbaugh, R Rosansky, J Taylor, S Van Stone, W TI UPBEAT: The impact of a psychogeriatric intervention in VA medical centers SO MEDICAL CARE LA English DT Article DE mental health; veterans; costs; comorbid conditions ID MAJOR DEPRESSIVE DISORDER; IDENTIFICATION TEST AUDIT; SF-36 HEALTH SURVEY; GENERAL-POPULATION; SYMPTOMATIC DEPRESSION; ELDERLY PATIENTS; MENTAL-HEALTH; COST-OFFSET; CARE COSTS; OUTCOMES AB BACKGROUND. The Unified Psychogeriatric Biopsychosocial Evaluation and Treatment (UPBEAT) program provides individualized interdisciplinary mental health treatment and care coordination to elderly veterans whose comorbid depression, anxiety, or alcohol abuse may result in overuse of inpatient services and underuse of outpatient services, OBJECTIVES. TO determine whether proactive screening of hospitalized patients can identify unrecognized comorbid psychiatric conditions and whether comprehensive assessment and psychogeriatric intervention can improve care while reducing inpatient use. DESIGN, Randomized trial, SUBJECTS. Veterans aged 60 and older hospitalized for nonpsychiatric medical or surgical treatment in 9 VA sites (UPBEAT, 814; usual care, 873). MEASURES. The Mental Health Inventory (MHI) anxiety and depression subscales, the Alcohol Use Disorder Identification Test (AUDIT) scores, RAND 36-Item Health Survey Short Form (SF-36), inpatient days and costs, ambulatory care clinic stops and costs, and mortality and readmission rates. RESULTS. Mental health and general health status scores improved equally from baseline to 12-month follow-up in both groups. UPBEAT increased outpatient costs by $1,171 (P <0.001) per patient, but lowered inpatient costs by $3,027 (P = 0.017), for an overall savings of $1,856 (P = 0.156), Inpatient savings were attributable to fewer bed days of care (3.30 days; P = 0.016) rather than fewer admissions. Patients with 1 or more pre-enrollment and postenrollment hospitalizations had the greatest overall savings ($6,015; P = 0.069), CONCLUSIONS, UPBEAT appears to accelerate the transition from inpatient to outpatient care for acute nonpsychiatric admissions. Care coordination and increased access to ambulatory psychiatric services produces similar improvement in mental health and general health status as usual care. C1 Univ Calif Los Angeles, Ctr Hlth Policy Res, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Stat Comp Ctr, Los Angeles, CA USA. Royal Melbourne Hosp, Dept Anesthesia, Melbourne, Vic, Australia. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Los Angeles, CA 90024 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Miami VAMC, GREEC, Miami, FL USA. VA Connecticut HealthCare Syst, West Haven, CT USA. VA Natl Headquarters, Washington, DC USA. RP Kominski, G (reprint author), Univ Calif Los Angeles, Ctr Hlth Policy Res, Sch Publ Hlth, 10911 Weyburn Ave,Ste 300, Los Angeles, CA 90024 USA. RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X NR 56 TC 18 Z9 18 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2001 VL 39 IS 5 BP 500 EP 512 DI 10.1097/00005650-200105000-00010 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 426TN UT WOS:000168364600010 PM 11317098 ER PT J AU Staab, JP Datto, CJ Weinrieb, RM Gariti, P Rynn, M Evans, DL AF Staab, JP Datto, CJ Weinrieb, RM Gariti, P Rynn, M Evans, DL TI Detection and diagnosis of psychiatric disorders in primary medical care settings SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; CATCHMENT-AREA SITES; ALZHEIMERS-DISEASE; MENTAL-DISORDERS; GERIATRIC DEPRESSION; ANXIETY DISORDERS; ALCOHOL-PROBLEMS; UNITED-STATES; OLDER ADULTS; EPIDEMIOLOGY AB During the last decade, an increasing amount of research has focused on developing efficient and reliable methods for detecting and diagnosing psychiatric disorders within the practical constraints of day-to-day primary medical practice. Specifically, clinical investigators have translated the psychiatric nomenclature into streamlined assessment tools that are geared toward the most common psychiatric illnesses in primary care populations. This article reviews the most effective of these tools for depression, anxiety, cognitive impairment, and substance-related problems. In each section, special attention is paid to the challenge of diagnosing these illnesses in older individuals. C1 Univ Penn Hlth Syst, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn Hlth Syst, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Staab, JP (reprint author), Hosp Univ Penn, Dept Psychiat, Founders Pavilion F11-015,3400 Spruce St, Philadelphia, PA 19104 USA. RI Staab, Jeffrey/B-8792-2015 OI Staab, Jeffrey/0000-0002-1516-3131 NR 75 TC 34 Z9 36 U1 8 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2001 VL 85 IS 3 BP 579 EP + DI 10.1016/S0025-7125(05)70330-8 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 431BA UT WOS:000168611000003 PM 11349474 ER PT J AU Goff, DC Heckers, S Freudenreich, O AF Goff, DC Heckers, S Freudenreich, O TI Schizophrenia SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID MAGNETIC-RESONANCE SPECTROSCOPY; MEDIAL TEMPORAL-LOBE; CEREBRAL BLOOD-FLOW; POSITRON-EMISSION TOMOGRAPHY; HIPPOCAMPAL PYRAMIDAL CELL; BASAL GANGLIA; TARDIVE-DYSKINESIA; PREFRONTAL CORTEX; NEGATIVE SYMPTOMS; NEURONAL DENSITY AB Schizophrenia is a chronic psychiatric illness characterized by psychosis, "negative symptoms," apathy and withdrawal, subtle cognitive deficits, a lack of insight, and deterioration of functioning. Although the etiology has not been fully established, schizophrenia clearly has a genetic component. Abnormalities of cellular distribution have been observed in postmortem brain, and abnormal patterns of brain activation have been observed in neuroimaging studies. Antipsychotic medication controls most symptoms, although patients often remain disabled by the illness and at risk for relapse. Because the newer antipsychotics seem to be more effective for cognitive deficits and for apathy their use has facilitated advances in psychosocial rehabilitation of individuals with this illness. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02115 USA. RP Goff, DC (reprint author), 25 Staniford St, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 228 TC 21 Z9 22 U1 7 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2001 VL 85 IS 3 BP 663 EP + DI 10.1016/S0025-7125(05)70335-7 PG 28 WC Medicine, General & Internal SC General & Internal Medicine GA 431BA UT WOS:000168611000008 PM 11349479 ER PT J AU Raskind, MA Peskind, ER AF Raskind, MA Peskind, ER TI Alzheimer's disease and related disorders SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED TRIAL; LEWY BODY DEMENTIA; DOUBLE-BLIND TRIAL; BEHAVIORAL DISTURBANCES; CONTROLLED MULTICENTER; CHOLINERGIC NEURONS; SENILE DEMENTIA; SELECTIVE LOSS; DEPRESSION AB Better understanding of the pathophysiology of Alzheimer's disease (AD) and results of empiric trials in AD of drugs effective for behavioral disturbances in younger nondemented patients have provided useful guidelines for the management of the cognitive deficits and noncognitive behavioral disturbances expressed in this increasingly common disorder. The cholinesterase inhibitors modestly improve cognitive function and stabilize cognitive and functional decline. The selective serotonin reuptake inhibitor antidepressants seem effective and well-tolerated for treatment of depression in AD. The atypical antipsychotics are effective for psychosis and disruptive agitation, and they are better tolerated. than typical antipsychotics, particularly in the Lewy body variant of AD. Increased understanding of the pathogenesis of AD has stimulated promising new approaches toward the ultimate goal of disease prevention. C1 Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. Univ Washington, Alzheimer Dis Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Raskind, MA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 66 TC 16 Z9 16 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2001 VL 85 IS 3 BP 803 EP + DI 10.1016/S0025-7125(05)70341-2 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 431BA UT WOS:000168611000014 PM 11349485 ER PT J AU Ubel, PA Baron, J Asch, DA AF Ubel, PA Baron, J Asch, DA TI Preference for equity as a framing effect SO MEDICAL DECISION MAKING LA English DT Article DE survey; public attitudes; equity; framing effect ID COST-EFFECTIVENESS ANALYSIS; HEALTH-CARE; EFFICIENCY; DECISION; OREGON; QALYS; RISK; LIFE AB Background In previous studies, the authors found that most people, given a fixed budget, would rather offer a less effective screening test to 100% of a Medicaid population than a more effective test to 50% of the population. In a subsequent study, the authors found that the number of people preferring the less effective screening test was dramatically reduced when the percentage of Medicaid enrollees receiving it was less than 100. In this article, 2 new studies are reported that explore whether people's preferences for equity versus efficiency are susceptible to a framing effect. Methods. In 2 studies, the authors presented subjects with multiple scenarios involving screening tests that vary in the proportion of people who could receive the tests within a budget constraint and the number of people whose lives each test would save. Across scenarios, the proportion of Medicaid enrollees who could receive each test was varied, as was the question of whether scenarios involved Medicaid enrollees from the same or a different state. In addition, the authors varied the order in which subjects received the scenarios. Results. In the 1st study, people's preferences for equity over efficiency varied significantly depending on the way situations were framed. Preference for equity was stronger when the more widely distributed choice covered the entire population than when it covered only half the population (P < 0.001). In addition, people's preferences were susceptible to order effects, with preference for equity being significantly stronger when the 1 st scenario received by subjects involved 1 screening test that could be offered to the entire population (P < 0.001). In the 2nd study, preferences for equity over efficiency diminished even when the different framings were descriptions of identical circumstances-preference for equity was significantly reduced when the population to be screened was framed broadly, in terms of the percentage of patients across 2 states who could receive testing rather than narrowly, in terms of the percentages of patients in 1 state who could receive testing (P = 0.04). Conclusion. Policy planners should be careful about accepting public preferences for equity over efficiency at face value, because such preferences can be dramatically influenced by framing effects and order effects. C1 Univ Michigan, Sch Med, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Vet Affairs Med Ctr, Ann Arbor, MI USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Ubel, PA (reprint author), Univ Michigan, Sch Med, Div Gen Internal Med, 300 N Ingalls,Room 7C27, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [R01 CA 78052-01] NR 30 TC 24 Z9 24 U1 1 U2 3 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 MAY-JUN PY 2001 VL 21 IS 3 BP 180 EP 189 DI 10.1177/02729890122062479 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 469EN UT WOS:000170801800003 PM 11386625 ER PT J AU Ubel, PA Loewenstein, G Hershey, J Baron, J Mohr, T Asch, DA Jepson, C AF Ubel, PA Loewenstein, G Hershey, J Baron, J Mohr, T Asch, DA Jepson, C TI Do nonpatients underestimate the quality of life associated with chronic health conditions because of a focusing illusion? SO MEDICAL DECISION MAKING LA English DT Article DE general public survey; utility measurement; quality of life measurement ID DURABILITY BIAS; RESPONSE SHIFT AB Background A number of studies show that the general public often estimates that the quality of life (QOL) associated with various health conditions is worse than patients say it is. These studies raise the possibility that people overestimate the impact that unfamiliar health conditions will have on their quality of life. One possible reason people overestimate this is because they are susceptible to a focusing illusion-when asked to imagine themselves in unfamiliar circumstances, people overestimate the emotional impact of those features of their life that would change. Methods. The authors surveyed members of the general public to test the hypothesis that their QOL ratings of hypothetical health conditions would be higher (indicating a better quality of life) after thinking about how the health condition would affect a broad range of life domains. Across 3 experiments, the authors varied the health conditions people were asked to consider (either paraplegia, below-the-knee amputation, or partial blindness), the life domains they were asked to consider, the response mode with which they evaluated how each health condition would affect each life domain, whether subjects rated the health condition before and after considering life domains or only after, and whether subjects rated their own current quality of life first. Results. Across 3 experiments, using 10 different questionnaire versions, only 1 instance was found in which subjects' ratings were significantly higher after thinking about the effect of the health condition on life domains than before, and the magnitude of this increase was small. Conclusion. It could not be established that a focusing illusion contributes significantly to the discrepancy in QOL ratings of patients and nonpatients. Further research should explore other factors that could contribute to the discrepancy or other ways of testing for the influence of a focusing illusion. C1 Univ Michigan, Sch Med, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Vet Affairs Med Ctr, Ann Arbor, MI USA. Program Improving Hlth Care Decis, Ann Arbor, MI USA. Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Ubel, PA (reprint author), 300 N Ingalls,Room 7C27, Ann Arbor, MI 48109 USA. FU AHRQ HHS [R01 HS12073-01] NR 16 TC 61 Z9 64 U1 3 U2 7 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 MAY-JUN PY 2001 VL 21 IS 3 BP 190 EP 199 DI 10.1177/02729890122062488 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 469EN UT WOS:000170801800004 PM 11386626 ER PT J AU Cooper, RA AF Cooper, RA TI Advances in wheelchair and related technologies SO MEDICAL ENGINEERING & PHYSICS LA English DT Editorial Material C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Excellence Wheelchairs & Related Technol, Human Engn Res Labs, Pittsburgh, PA USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD MAY PY 2001 VL 23 IS 4 BP III EP IV DI 10.1016/S1350-4533(01)00071-6 PG 2 WC Engineering, Biomedical SC Engineering GA 452EZ UT WOS:000169845700001 ER PT J AU Dvorznak, MJ Cooper, RA O'Connor, TJ Boninger, ML Fitzgerald, SG AF Dvorznak, MJ Cooper, RA O'Connor, TJ Boninger, ML Fitzgerald, SG TI Kinematic comparison of Hybrid II test dummy to wheelchair user SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE safety; falls; hybrid test dummies; injuries; modeling ID ACCIDENTS; MOMENTS; FORCES AB Hybrid test dummies provide a safe alternative to human subjects when investigating mechanisms of wheelchair tips and falls. The data that researchers acquire from these test dummies are more useful if the test dummy represents the population beings studied. The goal of this study was to measure the validity of a 50th percentile Hybrid II test dummy (HTD) as an accurate representation of a wheelchair user. A test pilot with T8 paraplegia due to traumatic spinal cord injury served as a basis for validation. Simple modifications were made to the HTD to approximate the trunk stability characteristics of a person with a spinal cord injury. An HTD, a modified HTD, and a human test pilot were seated in an electric-powered wheelchair and several braking tests performed. The standard HTD underestimated the kinematics when compared to the test pilot. The modified HTD had less trunk stability than the standard HTD during all braking methods. The modified HTD and wheelchair test pilot had similar trunk stability characteristics during kill switch and joystick full-reverse braking conditions. The modified HTD is a satisfactory representation of a wheelchair user with a spinal cord injury; however, the modified test dummy underestimates the trunk dynamics during the less extreme joystick release braking. Work should continue on the development of a low-speed, low-impact test dummy that emulates the wheelchair user population. (C) 2001 IPEM. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst,Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. Univ Pittsburgh, VA Pittsburgh Healthcare Syst,Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Dept Phys Med & Rehabil, Pittsburgh, PA 15206 USA. Univ Pittsburgh, VA Pittsburgh Healthcare Syst,Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Dept Bioengn, Pittsburgh, PA 15206 USA. RP Dvorznak, MJ (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst,Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 12 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD MAY PY 2001 VL 23 IS 4 BP 239 EP 247 DI 10.1016/S1350-4533(01)00025-X PG 9 WC Engineering, Biomedical SC Engineering GA 452EZ UT WOS:000169845700002 PM 11427361 ER PT J AU O'Connor, TJ Fitzgerald, SG Cooper, RA Thorman, TA Boninger, ML AF O'Connor, TJ Fitzgerald, SG Cooper, RA Thorman, TA Boninger, ML TI Does computer game play aid in motivation of exercise and increase metabolic activity during wheelchair ergometry? SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE wheelchairs; exercise; video game ID SPINAL-CORD INJURIES; VIDEO-GAME; DISABILITIES; PROPULSION; CHILDREN; SYSTEM; USERS AB GAME(Wheels) is an interface between a portable roller system and a computer that enables a wheelchair user to play commercially available computer video games. The subject controls the game play with the propulsion of their wheelchair's wheels on the rollers. The purpose of this study was to investigate whether using the GAME(Wheels) System during wheelchair propulsion exercise can help increase the individual's physiological response and aid in the motivation to exercise. Fifteen subjects participated in this study. The subjects propelled their wheelchairs on a portable roller that was equipped with the GAME(Wheels) System. There were two exercise trials consisting of 2 min of warm-up, 16 min of exercise and 2 min of cool-down, Physiological data (ventilation rate, oxygen consumption, heart rate) were collected. A significant difference (P < 0.05) was found between exercise with GAME(Wheels) versus without GAME(Wheels) for average ventilation rate and average oxygen consumption. The differences were found during time periods of transition from warm-up to exercise, and before and after the midpoint of exercise. Written questionnaires showed that 87% of the individuals tested reported the system would help them work out on a regular basis. Playing the video game helped these individuals to reach their exercise training zone faster and maintain it for the entire exercise trial. Published by Elsevier Science Ltd on behalf of IPEM. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Div Phys Med & Rehabil, Pittsburgh, PA 15260 USA. RP Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, 7180 Highland Dr, Pittsburgh, PA 15206 USA. RI Winstein, Carolee/A-8375-2008; OI Boninger, Michael/0000-0001-6966-919X NR 21 TC 18 Z9 18 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD MAY PY 2001 VL 23 IS 4 BP 267 EP 273 DI 10.1016/S1350-4533(01)00046-7 PG 7 WC Engineering, Biomedical SC Engineering GA 452EZ UT WOS:000169845700005 PM 11427364 ER PT J AU Koontz, AM Cooper, RA Boninger, ML AF Koontz, AM Cooper, RA Boninger, ML TI An autoregressive modeling approach to analyzing wheelchair propulsion forces SO MEDICAL ENGINEERING & PHYSICS LA English DT Article; Proceedings Paper CT Annual RESNA Conference CY JUN 26-30, 1999 CL LONG BEACH, CALIFORNIA SP RESNA DE autoregressive modeling; wheelchair propulsion biomechanics; asymmetry; spinal cord injury ID SPEEDS AB Biomechanical signals collected during wheelchair propulsion are often analyzed by computing averages and/or peak values over several strokes. Due to the complex nature of the signals, this type of analysis may not be specific to identifying factors that may predispose a wheelchair user to joint pain/injury. Hence, a new technique is introduced thai uses a system identification approach, autoregressive (AR) modeling, to analyze wheelchair propulsion force waveforms. In this application an AR method was used to create a model force waveform based on current and past values of digital pushrim force data. The feasibility of the AR modeling method over point-wise methods to detect asymmetry among force waveforms was tested with a group of 20 wheelchair users. Subjects propelled at a constant 0.9 m/s on a roller system during which 20 s of force data were collected from the SMART(Wheels), force and torque sensing pushrims. Both methods showed that the wheelchair users as a group propelled evenly, however, individual analysis using the AR model error estimates indicated that twenty-five percent demonstrated significant asymmetry in their force waveforms. If only point-wise means and variances of the applied bilateral forces were considered, most subjects would have appeared symmetrical. Thus, the AR modeling approach is more sensitive to detecting anomalies in propulsion technique. Published by Elsevier Science Ltd on behalf of IPEM. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Ctr Biotechnol & Bioengn 300, Dept Bioengn, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr Hlth Syst, Div Phys Med & Rehabil, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. RP Koontz, AM (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, 5044 Forbes Tower, Pittsburgh, PA 15261 USA. OI Boninger, Michael/0000-0001-6966-919X NR 12 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD MAY PY 2001 VL 23 IS 4 BP 285 EP 291 DI 10.1016/S1350-4533(00)00082-5 PG 7 WC Engineering, Biomedical SC Engineering GA 452EZ UT WOS:000169845700007 PM 11427366 ER PT J AU Xu, R Adak, S AF Xu, R Adak, S TI Survival analysis with time-varying relative risks: A tree-based approach SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE change point; classification and regression tree; maximized score test; non-proportional hazards; time-varying regression effect ID NUISANCE PARAMETER; REGRESSION; STATISTICS; SPLINES; MODELS AB A tree-based method for estimating time-varying effects of baseline patient characteristics on survival is introduced. A Cox-type model for censored survival data is used in which the time-varying relative risks are modelled as piecewise constants. The tree method consists of three steps: 1. Growing the tree, in which a fast algorithm using maximized score statistics is utilized to determine the optimal change points; 2. A pruning algorithm is applied to obtain more parsimonious models; 3. Selection of a final tree, which may be either via bootstrap resampling or based on a measure of explained variation. The piecewise constant model is more suitable for clinical interpretation of the regression parameters than the more continuously time-varying models (spline, loess, etc.) that have been proposed previously. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. RP Xu, R (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA39929] NR 23 TC 4 Z9 4 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD MAY PY 2001 VL 40 IS 2 BP 141 EP 147 PG 7 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 441BR UT WOS:000169211600016 PM 11424300 ER PT J AU Datta, MW Macri, E Signoretti, S Renshaw, AA Loda, M AF Datta, MW Macri, E Signoretti, S Renshaw, AA Loda, M TI Transition from in situ to invasive testicular germ cell neoplasia is associated with the loss of p21 and gain of mdm-2 expression SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 23-31, 2000 CL NEW ORLEANS, LOUISIANA SP US & Canadian Acad Pathol DE testis; germ cell tumors; p53; p21; mdm-2; intratubular germ cell neoplasia ID WILD-TYPE P53; TUMORS; GENE; DEGRADATION; PROTEIN; TESTIS AB Introduction: The tumor suppressor gene p53 has been shown to transcriptionally regulate expression of the cell cycle dependent kinase inhibitor p21. p53 is in turn regulated by the ubiquitin ligase mouse double minute-2 (mdm-2). We have set out to examine p21 expression in testicular germ cell tumors and its relationship with p53 and mdm-2 expression. Methods: Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded tissue for p53, p21, and mdm-2 in 31 testicular germ cell tumors, which included 17 pure seminomas and 14 mixed germ cell tumors composed predominantly of embryonal carcinoma. Twenty-seven cases contained adjacent areas of intratubular germ cell neoplasia (ITGCN), Results: 17 out of 17 seminomas and 14 out of 14 embryonal carcinomas expressed p53 in both ITGCN and the invasive tumor. In contrast, none of the 17 seminomas and only 2 of 14 embryonal carcinomas revealed positive staining for p21 protein. p21 expression was noted in 18 of 27 cases (67%) of ITGCN, and in 16 of these cases (89%) the corresponding invasive tumor had lost p21 expression. In nine additional cases p21 expression was absent in both the invasive and intratubular tumor, mdm-2 expression was present in 8 out of 17 (47%) seminomas and 13 out of 14 (93%) embryonal carcinomas but was present in only 2 out of 27 (7%) cases of ITGCN. Statistically significant associations for loss of p21 and gain of mdm-2 expression in invasive tumors were present (P < .0001). Conclusions: The co-expression of p53 and p21 in ITGCN is consistent with preservation of p53-directed induction of p21. The loss of p21 expression in invasive tumors suggests a disruption of the p53 regulatory pathway. The inverse correlation of p21 and mdm-2 expression in both ITGCN and invasive tumors could indicate that loss of the functional p53 regulatory pathway may be correlated with the onset of mdm-2 expression. These results raise the possibility that the loss of p21 expression may be associated with the development of invasive germ cell tumors from ITGCN. Persistent p53 expression in the presence of mdm-2 suggests that in testicular germ cell tumors, while mdm-2 can block the transactivation potential of p53, it can no longer target p53 for degradation. C1 Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. Baptist Hosp Miami, Miami, FL USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Tumor Biol, Boston, MA 02115 USA. RP Datta, MW (reprint author), Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Dept Pathol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 17 TC 40 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2001 VL 14 IS 5 BP 437 EP 442 DI 10.1038/modpathol.3880331 PG 6 WC Pathology SC Pathology GA 433ZZ UT WOS:000168791800011 PM 11353054 ER PT J AU Dong, HY Harris, NL Preffer, FI Pitman, MB AF Dong, HY Harris, NL Preffer, FI Pitman, MB TI Fine-needle aspiration biopsy in the diagnosis and classification of primary and recurrent lymphoma: A retrospective analysis of the utility of cytomorphology and flow cytometry SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 08, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE cytology; diagnosis; fine needle aspiration biopsy; flow cytometry; lymphoma; subclassification ID NON-HODGKINS-LYMPHOMA; MALIGNANT-LYMPHOMA; FOLLICULAR LYMPHOMA; CYTOLOGY DIAGNOSIS; SUBCLASSIFICATION; HYPERPLASIA; NEOPLASMS; PCR AB We retrospectively reviewed our experience with the fine-needle aspiration biopsy (FNAB) diagnosis of primary and recurrent lymphoma to assess the ability of cytomorphology with and without ancillary now cytometry (PCM) analysis to diagnose and subclassify these tumors according to the Revised European-American Lymphoma/World Health Organization classifications. We reviewed 139 consecutive FNABS of 84 primary and 55 recurrent lymphomas. FCM was successful in 105 (75%) cases. The overall results, including cases without FCM, included 93/139 (67%) true positive, 7 (5%) false negative, and 39 indeterminate (27 [19%] suspicious and 12 [9%] atypical) diagnoses of lymphoma In cases with FCM, there were 80/105 (77%) true positive, no false negative, and 25 indeterminate diagnoses (15 [14%] suspicious and 10 [9%] atypical). The overall results of the 84 primary lymphomas were 55 (67%) true positive, 5 (5%) false negative, and 24 indeterminate (14[16%] suspicious and 10 [12%] atypical) diagnoses for lymphoma Of the 68 primary lymphomas analyzed with FCM, 50 [74%] were true positives, and 28 were indeterminate (11 [16%] suspicious and 7 [10%] atypical). There were no false negatives. Diagnostic accuracy varied among lymphoma subtypes. Subclassification of the positive cases were initially conclusive in only 55/93 cases (59%). However, a retrospective review of the morphologic together with FCM data in 15 of the 23 unclassified cases improved the overall subclassification of positive cases to 77%. Subclassification was best in small lymphocytic lymphoma/chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, Burkitt's lymphoma, mantle cell lymphoma, and plasmacytoma (all 100%). Subclassification was poor in marginal-zone lymphoma (33%), and initially as well in diffuse large B-cell lymphoma (62%), but it improved on review (95%), as did subclassification of follicular lymphoma (77 to 100% on review). Hodgkin's disease was recognized as malignant in only 44% of the cases (7/16) and was classified as such based on morphology alone. This review of our early efforts to diagnose and subclassify lymphoma with FNAB and FCM indicates that although a diagnosis and proper subclassification of lymphoma can be made with certainty in the majority of cases, recurrent or primary, it requires close coordination of cytomorphology and immunophenotyping data, which often comes with close cooperation of cytopathologists and hematopathologists. A mere cytological diagnosis of positive for lymphoma is no longer acceptable if FNAB is to become an independent diagnostic tool for lymphoma. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Pitman, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 34 TC 100 Z9 106 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2001 VL 14 IS 5 BP 472 EP 481 DI 10.1038/modpathol.3880336 PG 10 WC Pathology SC Pathology GA 433ZZ UT WOS:000168791800016 PM 11353059 ER PT J AU Waltregny, D Leav, I Signoretti, S Soung, P Lin, D Merk, F Adams, JY Bhattacharya, N Cirenei, N Loda, M AF Waltregny, D Leav, I Signoretti, S Soung, P Lin, D Merk, F Adams, JY Bhattacharya, N Cirenei, N Loda, M TI Androgen-driven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; MAMMARY-CARCINOMA CELLS; GROWTH ARREST; RAT PROSTATE; CYCLE ARREST; TUMOR-CELLS; MEDIATED DEGRADATION; RESTRICTION POINT; PROGRAMMED DEATH; CDK INHIBITOR AB Androgens control both growth and differentiation of the normal prostate gland. However, the mechanisms by which androgens act upon the cell cycle machinery to regulate these two fundamental processes are largely unknown. The cyclin-dependent kinase (cdk) inhibitor p27 Is a negative cell cycle regulator involved in differentiation-associated growth arrest. Here, we investigate the role and regulation of p27 in the testosterone proprionate (TP)-stimulated regeneration of the ventral prostate (VP) of castrated rats. Continuous TP administration to castrated rats triggered epithelial cell proliferation, which peaked at 72 h, and then declined despite further treatment. Castration-induced atrophy of the VP was associated with a significant increase in p27 expression as compared with the VP of intact animals. Twelve hours after the initiation of androgen treatment, total p27 levels as well as its fraction bound to cdk2, its main target, significantly dropped in the VP of castrated rats. Thereafter, concomitantly to the induction of epithelial cell proliferation, the glandular morphology of VP was progressively restored at 48-96 h of TP treatment. During this period of the regenerative process, whereas both proliferating basal and secretory epithelial cells did not express p27, the protein was selectively up-regulated in the nonproliferating secretory epithelial compartment This up-regulation of p27 expression was coincident with an increase in its association with, and presumably inhibition of, cdk2. At each time point of TP treatment, p27 abundance in the VP was inversely correlated with the level of its proteasome-dependent degradation activity measured in vitro in VP lysates, whereas only slight changes in the amount of p27 transcripts were detected. In addition, the antiandrogen flutamide blocked maximal TP-induced p27 degradation completely. Finally, the expression of skp2, the ubiquitin ligase that targets p27 for degradation, was seen to increase with androgen administration, preceding maximal proliferation and concomitantly to augmented p27 degradation activity. Taken together, our data indicate that androgens mediate both proliferation and differentiation signals in normal prostate epithelial cells in vivo, through regulation of p27. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana Bldg 740B,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5RO1CA-81755-03] NR 78 TC 63 Z9 64 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 2001 VL 15 IS 5 BP 765 EP 782 DI 10.1210/me.15.5.765 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 427FB UT WOS:000168393200007 PM 11328857 ER PT J AU Ito, Y Pandey, P Sporn, MB Datta, R Kharbanda, S Kufe, D AF Ito, Y Pandey, P Sporn, MB Datta, R Kharbanda, S Kufe, D TI The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism SO MOLECULAR PHARMACOLOGY LA English DT Article ID MYELOID-LEUKEMIA CELLS; CYTOCHROME-C; 1-BETA-D-ARABINOFURANOSYLCYTOSINE INCORPORATION; 2-CYANO-3,12-DIOXOOLEAN-1,9-DIEN-28-OIC ACID; INCREASED EXPRESSION; ANTICANCER DRUGS; DNA; ACTIVATION; INDUCTION; DEATH AB The oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a multifunctional molecule that induces monocytic differentiation of human myeloid leukemia cells and inhibits proliferation of diverse human tumor cell lines. The present studies on human osteosarcoma cells demonstrate that CDDO induces mitochondrial cytochrome c release, caspase-3 activation, and internucleosomal DNA fragmentation. Overexpression of the caspase-8 inhibitor CrmA blocked CDDO-induced cytochrome c release and apoptosis. By contrast, overexpression of the antiapoptotic Bcl-x(L) protein blocked CDDO-induced cytochrome c release, but only partly inhibited caspase-3 activation and apoptosis. In concert with these findings, we demonstrate that CDDO: 1) activates caspase-8 and thereby caspase-3 by a cytochrome c-independent mechanism and 2) induces cytochrome c release by caspase-8-dependent cleavage of Bid. The results also demonstrate that treatment of osteosarcoma cells with CDDO induces differentiation, as assessed by alkaline phosphatase activity and osteocalcin production, and that this response is abrogated in cells that overexpress CrmA. These findings demonstrate that CDDO induces both osteoblastic differentiation and apoptosis by caspase-8-dependent mechanisms. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Med Sch, Norris Cotton Canc Ctr, Hanover, NH USA. Dartmouth Med Sch, Dept Pharmacol, Hanover, NH USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42802] NR 34 TC 108 Z9 114 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 2001 VL 59 IS 5 BP 1094 EP 1099 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 422HP UT WOS:000168112700019 PM 11306692 ER PT J AU Aifantis, I Gounari, F Scorrano, L Borowski, C von Boehmer, H AF Aifantis, I Gounari, F Scorrano, L Borowski, C von Boehmer, H TI Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-kappa B and NFAT SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; ALLELIC EXCLUSION; LYMPHOCYTE DEVELOPMENT; THYMOCYTE DEVELOPMENT; TRANSCRIPTION FACTORS; INDUCED APOPTOSIS; BETA-CHAIN; GENE-EXPRESSION; STORE DEPLETION; CALCIUM CURRENT AB Pre-T cell antigen receptor (pre-TCR) signaling plays a crucial role in the development of immature T cells,Although certain aspects of proximal pre-TCR signaling have been studied, the intermediate signal transducers and the distal transcription modulators have been poorly characterized. We report here a correlation between pre-TCR signaling and a biphasic rise in the cytosolic Ca2+ concentration. In addition, we show that constitutive pre-TCR signaling is associated with an increased rate of Ca2+ influx through store-operated plasma membrane Ca2+ channels,We show also that the biphasic nature of the observed pre-TCR-induced rise in cytosolic Ca2+ differentially modulates the activities of the transcription factors NF-kappaB and NFAT in developing T cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St, Boston, MA 02115 USA. RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 FU NIAID NIH HHS [R01 AI45846] NR 59 TC 129 Z9 130 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2001 VL 2 IS 5 BP 403 EP 409 PG 7 WC Immunology SC Immunology GA 429ZZ UT WOS:000168549800012 PM 11323693 ER PT J AU Takagi, J Erickson, HP Springer, TA AF Takagi, J Erickson, HP Springer, TA TI C-terminal opening mimics 'inside-out' activation of integrin alpha 5 beta 1 SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID ELECTRON-MICROSCOPY; CRYSTAL-STRUCTURE; COUPLED RECEPTOR; LIGAND-BINDING; COILED-COIL; ALPHA(IIB)BETA(3); CONFORMATION; ANTIBODY; SUBUNIT; REGION AB Integrins are adhesion molecules that convey signals both to and from the cytoplasm across the plasma membrane. In resting cells, integrins in a low affinity state can be activated by 'inside-out signaling' in which signals affecting integrin heterodimer cytoplasmic domains cause a conformational change in the integrin ligand-binding headpiece connected to the membrane by two long, similar to 16 nm stalks. Here we demonstrate a mechanism for conveying a conformational change over the long distance from the plasma membrane to the headpiece. We prepared soluble, alpha5 beta1 integrin heterodimer extracellular fragments in which interactions between alpha- and beta -subunit cytoplasmic domains were replaced with an artificial clasp. Release of this C-terminal clasp by specific protease cleavage resulted in an similar to 14 nm separation of the stalks coupled to increased binding to fibronectin. This activation did not require any associated molecules or clustering and was observed with physiological concentrations of divalent cations. These findings suggest that the overall mechanism for integrin inside-out activation involves the spatial separation of the cytoplasmic and/or transmembrane domains. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. RP Takagi, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 32 TC 181 Z9 185 U1 2 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAY PY 2001 VL 8 IS 5 BP 412 EP 416 DI 10.1038/87569 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 425WU UT WOS:000168315300012 PM 11323715 ER PT J AU Jara, A Chacon, C Valdivieso, A Aris, L Jalil, R Felsenfeld, AJ AF Jara, A Chacon, C Valdivieso, A Aris, L Jalil, R Felsenfeld, AJ TI Effect of calcitriol treatment and withdrawal on hyperparathyroidism in haemodialysis patients with hypocalcaemia SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE calcitriol; calcium; parathyroid function; parathyroid hormone; phosphate ID PARATHYROID-HORMONE SECRETION; PTH-CALCIUM CURVE; SECONDARY HYPERPARATHYROIDISM; HEMODIALYSIS-PATIENTS; INTRAVENOUS CALCITRIOL; SET-POINT; SERUM-CALCIUM; DIALYSIS; THERAPY; ADAPTATION AB Background. Calcitriol is used to treat secondary hyperparathyroidism in dialysis patients. For similarly elevated parathyroid hormone (PTH) levels, the PTH response to calcitriol treatment is believed to he better in hypocalcaemic dialysis patients than in dialysis patients with higher serum calcium values. Furthermore, few studies have evaluated the rapidity of the rebound in serum PTH values after prolonged treatment with calcitriol. Our goal was to evaluate (i) the PTH response to calcitriol treatment in hypocalcaemic haemodialysis patients, (ii) the rapidity of rebound in PTH after calcitriol treatment was stopped, and (iii) whether the effect of calcitriol treatment on PTH levels could be separated from those produced by changes in serum calcium and phosphate values. Methods. Fight haemodialysis patients (29 +/- 3 years) with hypocalcaemia and hyperparathyroidism were treated thrice weekly with 2 mug of intravenous calcitriol and were dialysed with a 3.5 mEq/l calcium dialysate. Parathyroid function (PTH-calcium curve) was determined before and after 30 weeks of calcitriol treatment and 15 weeks after calcitriol treatment was stopped. Results, Pretreatment PTH and ionized calcium values were 90 +/- 127 pg/ml and 3.89 +/- 0.12 mg/dl (normal, 4.52 +/- 0.07 mg/dl). During calcitriol treatment, one patient did not respond? but basal (predialysis) PTH values in the other seven patients decreased from 846 +/- 129 to 72 +/- 12 pg/ml, P < 0.001 and in all seven patients, the decrease exceeded 85%. During the 15 weeks after calcitriol treatment was stopped, a slow rebound in basal PTH values in the seven patients was observed, 72 12 to 375 +/- 44 pg/ml. Covariance analysis was used to evaluate the three tests of parathyroid function (0, 30, and 45 weeks), and showed that calcitriol treatment was associated with reductions in maximal PTH values while reductions in basal PTH were affected by ionized calcium and serum phosphate. The basal/maximal PTH ratio and the set point of calcium were associated with changes in ionized calcium. Conclusions. In haemodialysis patients with hypocalcaemia, (li) moderate to severs hyperparathyroidism responded well to treatment with calcitriol, (ii) reductions in maximal PTH were calcitriol dependent while reductions in basal PTH were affected by the ionized calcium and serum phosphate concentrations, (iii) changes in the basal/maximal PTH ratio and the set point of calcium were calcium dependent, and (iv) the delaved rebound in basal PTH levels after withdrawal of calcitriol treatment may have been due to the long duration of treatment and the marked PTH suppression during treatment. C1 Pontificia Univ Catolica Chile, Hosp Clin, Dept Nephrol, Santiago, Chile. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Jara, A (reprint author), Pontificia Univ Catolica Chile, Hosp Clin, Dept Nephrol, Marcoleta 35, Santiago, Chile. NR 25 TC 2 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAY PY 2001 VL 16 IS 5 BP 1009 EP 1016 DI 10.1093/ndt/16.5.1009 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 430HT UT WOS:000168569000022 PM 11328908 ER PT J AU Rao, VLR Bowen, KK Dempsey, RJ AF Rao, VLR Bowen, KK Dempsey, RJ TI Transient focal cerebral ischemia down-regulates glutamate transporters GLT-1 and EAAC1 expression in rat brain SO NEUROCHEMICAL RESEARCH LA English DT Article DE EAAC1; focal cerebral ischemia; gene expressions; GLT-1; glutamate transporters; stroke ID ARTERY OCCLUSION; NEURONAL DEATH; CELL-DEATH; INJURY; GLAST; HIPPOCAMPUS; METABOLISM; RELEASE; MICE AB Transient focal cerebral ischemia leads to extensive excitotoxic neuronal damage in rat cerebral cortex. Efficient reuptake of the released glutamate is essential for preventing glutamate receptor over-stimulation and neuronal death. Present study evaluated the expression of the glial (GLT-1 and GLAST) and neuronal (EAAC1) subtypes of glutamate transporters after transient middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia in rats. Between 24h to 72h of reperfusion after transient MCAO, GLT-1 and EAAC1 protein levels decreased significantly (by 36% to 56%, p < 0.05) in the ipsilateral cortex compared with the contralateral cortex or sham control. GLT-1 and EAAC1 mRNA expression also decreased in the ipsilateral cortex of ischemic rats at both 24h and 72h of reperfusion, compared with the contralateral cortex or sham control. Glutamate transporter down-regulation may disrupt the normal clearance of the synaptically-released glutamate and may contribute to the ischemic neuronal death. C1 Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA. Univ Wisconsin, Cardiovasc Res Ctr, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Rao, VLR (reprint author), Univ Wisconsin, Dept Neurol Surg, F4-309 CSC,600 Highland Ave, Madison, WI 53792 USA. FU NINDS NIH HHS [NS31220, NS28000] NR 41 TC 71 Z9 76 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 2001 VL 26 IS 5 BP 497 EP 502 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 462VB UT WOS:000170439500007 PM 11513475 ER PT J AU Arnold, JB Liow, JS Schaper, KA Stern, JJ Sled, JG Shattuck, DW Worth, AJ Cohen, MS Leahy, RM Mazziotta, JC Rottenberg, DA AF Arnold, JB Liow, JS Schaper, KA Stern, JJ Sled, JG Shattuck, DW Worth, AJ Cohen, MS Leahy, RM Mazziotta, JC Rottenberg, DA TI Qualitative and quantitative evaluation of six algorithms for correcting intensity nonuniformity effects SO NEUROIMAGE LA English DT Article DE magnetic field inhomogeneity; MRI; tissue segmentation ID MRI; INHOMOGENEITY; FREQUENCY; FIELD; 1.5-T; COILS AB The desire to correct intensity nonuniformity in magnetic resonance images has led to the proliferation of nonuniformity-correction (NUC) algorithms with different theoretical underpinnings. In order to provide end users with a rational basis for selecting a given algorithm for a specific neuroscientific application, we evaluated the performance of six NUC algorithms. We used simulated and real MRI data volumes, including six repeat scans of the same subject, in order to rank the accuracy, precision, and stability of the nonuniformity corrections. We also compared algorithms using data volumes from different subjects and different (1.5T and 3.0T) MRI scanners in order to relate differences in algorithmic performance to intersubject variability and/or differences in scanner performance. In phantom studies, the correlation of the extracted with the applied nonuniformity was highest in the transaxial (left-to-right) direction and lowest in the axial. (top-to-bottom) direction. Two of the six algorithms demonstrated a high degree of stability, as measured by the iterative application of the algorithm to its corrected output. While none of the algorithms performed ideally under all circumstances, locally adaptive methods generally outperformed nonadaptive methods. (C) 2001 Academic Press. C1 Minneapolis VA Med Ctr, Serv Neurol, Minneapolis, MN 55417 USA. Minneapolis VA Med Ctr, PET Imaging Ctr, Minneapolis, MN 55417 USA. Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. Univ So Calif, Inst Signal & Image Proc, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Brain Mapping Ctr, Los Angeles, CA 90024 USA. RP Arnold, JB (reprint author), Minneapolis VA Med Ctr, Serv Neurol, 1 Vet Dr, Minneapolis, MN 55417 USA. RI Sled, John/D-8268-2012; Cohen, Mark/C-6610-2011 OI Sled, John/0000-0002-4461-283X; Cohen, Mark/0000-0001-6731-4053 FU NIMH NIH HHS [MH52176, MH57180]; NINDS NIH HHS [NS33718] NR 20 TC 114 Z9 115 U1 1 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2001 VL 13 IS 5 BP 931 EP 943 DI 10.1006/nimg.2001.0756 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 429CA UT WOS:000168497400015 PM 11304088 ER PT J AU Doherty, C AF Doherty, C TI Neurologic manifestations of thyroid disease SO NEUROLOGIST LA English DT Article DE hyperthyroidism; hypothyroidism; neuropsychiatric; myopathy neuropathy; Hashimoto's encephalopathy ID THYROTOXIC PERIODIC PARALYSIS; SEVERE GRAVES OPHTHALMOPATHY; SKELETAL-MUSCLE; HASHIMOTO ENCEPHALOPATHY; HYPOTHYROIDISM; HYPERTHYROIDISM; DIAGNOSIS; MYOPATHY; BRAIN; MECHANISMS AB BACKGROUND- The neurologic disorders associated with thyroid dysfunction span the entire spectrum of neurology. Symptoms range from disorders of emotion and higher cognitive function to movement disorders, neuromuscular diseases, and a range of rarer yet significant neurologic sequelae. REVIEW SUMMARY- Generally, the subject may be divided into the effects on the metabolism and development of neurologic structures in situations of intoxication or deprivation of thyroid hormones. Hyperthyroidism prominently causes neuropsychiatric abnormalities, neuromuscular disease, and a range of other disorders, such as dysthyroid orbitopathy, movement disorders, and neuropathies. Hypothyroidism has more significant effects on the developing brain, leading to long-lasting effects of congenital hypothyroidism. It also has a wide range of effects in the adult, including psychomotor slowing, neuropsychiatric disease, metabolic effects that can lead to seizures, encephalopathy, and coma, and neuromuscular disorders, such as myopathy and neuropathy. It is also associated with cerebellar ataxia, myasthenia gravis, and sleep apnea. CONCLUSIONS- The wide-ranging effects of thyroid hormone excess and depletion on the neurologic system have been given focus by recent advances in the understanding of the cellular and molecular effects of this important chemical. There is still much to understand and elucidate, particularly in the area of neuropsychiatric morbidity and cognitive change. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 93 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD MAY PY 2001 VL 7 IS 3 BP 147 EP 157 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 432FP UT WOS:000168681800002 ER PT J AU Bae, K Jin, XW Maywood, ES Hastings, MH Reppert, SM Weaver, DR AF Bae, K Jin, XW Maywood, ES Hastings, MH Reppert, SM Weaver, DR TI Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock SO NEURON LA English DT Article ID MAMMALIAN PERIOD GENES; KINASE-I-EPSILON; SUPRACHIASMATIC NUCLEUS; FIRING RHYTHMS; FEEDBACK LOOPS; MOUSE SCN; LIGHT; TRANSCRIPTION; EXPRESSION; REGULATORS AB The role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes. Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness. Clock gene RNA rhythms were blunted in the suprachiasmatic nucleus of mPer2 mutant mice, but not of mPER1-deficient mice. Peak mPER and mCRY1 protein levels were reduced in both lines. Behavioral rhythms of mPer1/mPer3 and mPer2/mPer3 double-mutant mice resembled rhythms of mice with disruption of mPer1 or mPer2 alone, respectively, confirming the placement of mPer3 outside the core circadian clockwork. In contrast, mPer1/mPer2 double-mutant mice were immediately arrhythmic. Thus, mPER1 influences rhythmicity primarily through interaction with other clock proteins, while mPER2 positively regulates rhythmic gene expression, and there is partial compensation between products of these two genes. C1 Massachusetts Gen Hosp, Lab Dev Chronobiol, MassGen Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Cambridge, Dept Anat, Cambridge CB2 3DY, England. MRC, Mol Biol Lab, Div Neurobiol, Cambridge CB2 2QH, England. RP Weaver, DR (reprint author), Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01655 USA. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [HD14427]; NINDS NIH HHS [NS39303] NR 44 TC 487 Z9 513 U1 6 U2 35 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 2001 VL 30 IS 2 BP 525 EP 536 DI 10.1016/S0896-6273(01)00302-6 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 436XW UT WOS:000168962000023 PM 11395012 ER PT J AU Breiter, HC Aharon, I Kahneman, D Dale, A Shizgal, P AF Breiter, HC Aharon, I Kahneman, D Dale, A Shizgal, P TI Functional imaging of neural responses to expectancy and experience of monetary gains and losses SO NEURON LA English DT Article ID MIDBRAIN DOPAMINE NEURONS; VENTRAL TEGMENTAL AREA; ORBITOFRONTAL CORTEX; BASOLATERAL AMYGDALA; NUCLEUS-ACCUMBENS; SELF-STIMULATION; HUMAN BRAIN; AFFECTIVE NEUROSCIENCE; FACIAL EXPRESSIONS; PREFRONTAL CORTEX AB Neural responses accompanying anticipation and experience of monetary gains and losses were monitored by functional magnetic resonance imaging. Trials comprised an initial "prospect" (expectancy) phase, when a set of three monetary amounts was displayed, and a subsequent "outcome" phase, when one of these amounts was awarded. Hemodynamic responses in the sublenticular extended amygdala (SLEA) and orbital gyrus tracked the expected values of the prospects, and responses to the highest value set of outcomes increased monotonically with monetary value in the nucleus accumbens, SLEA, and hypothalamus. Responses to prospects and outcomes were generally, but not always, seen in the same regions. The overlap of the observed activations with those seen previously in response to tactile stimuli, gustatory stimuli, and euphoria-inducing drugs is consistent with a contribution of common circuitry to the processing of diverse rewards. C1 Massachusetts Gen Hosp, Dept Radiol, Motivat & Emot Neurosci Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Concordia Univ, Ctr Studies Behav Neurobiol, Montreal, PQ H3G 1M8, Canada. Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA. RP Breiter, HC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Motivat & Emot Neurosci Ctr, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010; OI Shizgal, Peter/0000-0003-4265-0792 FU NCRR NIH HHS [P41-RR14075, R01-RR13609]; NINDS NIH HHS [R01-NS39581]; PHS HHS [00265, 09467] NR 96 TC 792 Z9 810 U1 8 U2 73 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 2001 VL 30 IS 2 BP 619 EP 639 DI 10.1016/S0896-6273(01)00303-8 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 436XW UT WOS:000168962000030 PM 11395019 ER PT J AU Castellon, SA Ganz, PA AF Castellon, SA Ganz, PA TI Cognitive function after systemic therapy for breast cancer - The Olin article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Greater Los Angeles VA Healthcare Syst, Neuropsychol Assessment Lab, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Canc Prevent & Control Res, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Div Canc Prevent & Control Res, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Castellon, SA (reprint author), Greater Los Angeles VA Healthcare Syst, Neuropsychol Assessment Lab, Los Angeles, CA 90024 USA. NR 5 TC 2 Z9 2 U1 0 U2 1 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2001 VL 15 IS 5 BP 622 EP + PG 2 WC Oncology SC Oncology GA 444AY UT WOS:000169376800013 ER PT J AU Hatton, MP Watkins, LM Rubin, PAD AF Hatton, MP Watkins, LM Rubin, PAD TI Orbital fractures in children SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2000 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID PEDIATRIC MAXILLOFACIAL TRAUMA; FACIAL FRACTURES; FLOOR FRACTURES; YOUNG-CHILDREN; MANAGEMENT; BLOWOUT; AGE; INJURY AB Purpose: To describe the demographics, etiologic factors, clinical presentations, and outcomes of orbital fractures in children. Methods: This was: a retrospective case series of 96 consecutive patients under 18 years of age with orbital fractures presenting to the Massachusetts Eye and Ear Infirmary, including both hospitalized and nonhospitalized patients. Results: Orbital fractures in children were most frequently the result of sports, assault, or motor vehicle accident. The majority of patients did not require hospitalization and were treated as outpatients. The medial wall and floor of the orbit were the most frequent locations of fracture. Approximately half of the patients in this series required surgery, most often for entrapment. There were no cases of persistent diplopia in patients in whom surgery was performed or was not indicated. Associated ocular injuries were observed in half of the patients. Conclusions: In this series of hospitalized and nonhospitalized patients, orbital fractures in children had a location pattern similar to that most frequently observed in adult patients (floor and medial wall). Orbital fractures in children frequently require surgery. The high prevalence of ocular injury in children with orbital fractures emphasizes the need for a comprehensive ophthalmic evaluation. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Oculoplast Surg Serv, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Oculoplast Surg Serv, Boston, MA 02114 USA. NR 35 TC 36 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD MAY PY 2001 VL 17 IS 3 BP 174 EP 179 DI 10.1097/00002341-200105000-00005 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 435EA UT WOS:000168863400005 PM 11388382 ER PT J AU Arnold, J Kilmartin, D Olson, J Neville, S Robinson, K Laird, A Richmond, C Farrow, A McKay, S Saperstein, DA Aaberg, TM Johnson, JB Waldron, R Loupe, D Gillman, J Myles, B Schachat, AP Bressler, NM Bressler, SB Nesbitt, P Porter, T Hawse, P Hartnett, M Eager, A Belt, J Cain, D Emmert, D George, T Herring, M McDonald, J Mones, J Corcostegui, B Gilbert, M Duran, N Sisquella, M Nolla, A Margalef, A Miller, JW Gragoudas, ES Lane, AM Emmanuel, N Holbrook, A Evans, C Lord, US Walsh, DK Callahan, CD DuBois, JL Lewis, H Kaiser, PK Holody, LJ Lesak, E Lichterman, S Siegel, H Fattori, A Ambrose, G Fecko, T Ross, D Burke, S Singerman, L Zegarra, H Novak, M Bartel, M Tilocco-DuBois, K Iic, M Schura, S Mayes, SJ Tanner, V Rowe, P Smith-Brewer, S Kukula, D Greanoff, G Daley, G DuBois, J Lehnhardt, D Fish, GE Jost, BF Anand, R Callanan, D Arceneaux, S Arnwine, J Ellenich, P King, J Aguado, H Rollins, R Jurklies, B Pauleikhoff, D Hintzmann, A Fischer, M Sowa, C Behne, E Pournaras, CJ Donati, G Kapetanios, AD Cavaliere, K Guney-Wagner, S Gerber, N Sickenberg, M Sickenberg, V Gans, A Hosner, B Sbressa, A Kozma, C Curchod, M Cancelli, SA Harding, S Yang, YC Briggs, M Briggs, S Tompkin, V Jackson, R Pearson, S Natha, S Sharp, J Lim, JI Flaxel, C Padilla, M Levin, L Walonker, F Cisneros, L Nichols, T Schmidt-Erfurth, U Barbazetto, I Laqua, H Kupfer, R Bulow, R Glisovic, B Bredfeldt, T Elsner, H Wintzer, V Bahlmann, D Michels, S Blumenkranz, MS Little, HL Jack, R Espiritu, LM Unyi, L Regan, J Lamborn, L Silvestri, C Rosa, RH Rosenfeld, PJ Lewis, ML Rodriguez, B Torres, A Munoz, N Contreras, T Galvez, M Hess, D Cubillas, T Rams, I Slakter, JS Sorenson, JA Bruschi, PA Burke, K Schnipper, E Maranan, L Scolaro, M Riff, M Agresta, E Johansson, I Dedorsson, I Stenkula, S Hvarfner, C Carlsson, T Liljedahl, AM Fallstrom, S Jacobsson, E Soubrane, G Kuhn, D Oubraham, H Benelhani, A Kunsch, A Delhoste, B Ziverec, G Lasnier, M Lobes, LA Olsen, K Bahr, BJ Worstell, NT Wilcox, LA Wellman, LA Vagstad, G Steinberg, D Campbell, A Dreyer, R Williamson, B Johnson, M Crider, H Margherio, RR Williams, GA Zajechowski, M Stanley, C Kulak, M Streasick, P Szdlowski, L Falk, R Shoichet, S Regan, G Manatrey, P Cumming, K Koenig, F Benchaboune, M Mezmate, K Fontanay, S Meredith, T Binning, J Gualdoni, J Boyd, L Ort, E Barts, B Allen, R Dahl, J Holle, T Harvey, PT Kaus, L Leuschner, D Bolychuk, S Hewitt, I Menchini, U Bandello, F Virgili, G Lanzetta, P Ambesi, M Pirracchio, A Tedeschi, M Potter, MJ Sahota, B Hall, L Stur, M Lukas, J Tittl, M Docker, S Vogl, K Bressler, SB Bressler, NM Pieramici, DJ Manos, KS Cooper, R Denbow, RL Lowery, ER Phillips, DA Thibeault, SK Tian, Y Harnett, M Hawse, P Black, N Escartin, P Hartley, D Haworth, P Hecker, T Hiscock, D Jamali, F Maradan, N North, J Norton, B Stapleton-Hayes, T Taylor, R Huber, G Deslandes, JY Fsadni, M Hess, I de Pommerol, H Bobillier, A Reaves, A Banasik, S Koester, J Gray, T Truett, K Baker, J McAlister, L Birch, R Strong, A Azab, M Buskard, N Manjuris, U Hao, Y Mason, M McCurry, U Barbazetto, I Birngruber, R Bressler, SB Bressler, NM Donati, G Fish, GE Gragoudas, ES Harvey, P Kaiser, PK Koester, JM Lewis, H Lim, JI Ma, C Miller, JW Mones, J Murphy, SA Pieramici, DJ Potter, MJ Pournaras, CJ Schachat, AP Schmidt-Erfurth, U Singerman, L Slakter, JS Soubrane, S Strong, HA van den Berg, H Williams, GA Bressler, NM Manjuris, U Strong, HA Beck, RW Bird, AC Coscas, G Deutman, A Jampol, L Klein, R Maguire, M Deslandes, JY Huber, G Miller, JW Sickenberg, M Rosenfeld, P Stur, M Arceneaux, S Margherio, RP Staflin, P AF Arnold, J Kilmartin, D Olson, J Neville, S Robinson, K Laird, A Richmond, C Farrow, A McKay, S Saperstein, DA Aaberg, TM Johnson, JB Waldron, R Loupe, D Gillman, J Myles, B Schachat, AP Bressler, NM Bressler, SB Nesbitt, P Porter, T Hawse, P Hartnett, M Eager, A Belt, J Cain, D Emmert, D George, T Herring, M McDonald, J Mones, J Corcostegui, B Gilbert, M Duran, N Sisquella, M Nolla, A Margalef, A Miller, JW Gragoudas, ES Lane, AM Emmanuel, N Holbrook, A Evans, C Lord, US Walsh, DK Callahan, CD DuBois, JL Lewis, H Kaiser, PK Holody, LJ Lesak, E Lichterman, S Siegel, H Fattori, A Ambrose, G Fecko, T Ross, D Burke, S Singerman, L Zegarra, H Novak, M Bartel, M Tilocco-DuBois, K Iic, M Schura, S Mayes, SJ Tanner, V Rowe, P Smith-Brewer, S Kukula, D Greanoff, G Daley, G DuBois, J Lehnhardt, D Fish, GE Jost, BF Anand, R Callanan, D Arceneaux, S Arnwine, J Ellenich, P King, J Aguado, H Rollins, R Jurklies, B Pauleikhoff, D Hintzmann, A Fischer, M Sowa, C Behne, E Pournaras, CJ Donati, G Kapetanios, AD Cavaliere, K Guney-Wagner, S Gerber, N Sickenberg, M Sickenberg, V Gans, A Hosner, B Sbressa, A Kozma, C Curchod, M Cancelli, SA Harding, S Yang, YC Briggs, M Briggs, S Tompkin, V Jackson, R Pearson, S Natha, S Sharp, J Lim, JI Flaxel, C Padilla, M Levin, L Walonker, F Cisneros, L Nichols, T Schmidt-Erfurth, U Barbazetto, I Laqua, H Kupfer, R Bulow, R Glisovic, B Bredfeldt, T Elsner, H Wintzer, V Bahlmann, D Michels, S Blumenkranz, MS Little, HL Jack, R Espiritu, LM Unyi, L Regan, J Lamborn, L Silvestri, C Rosa, RH Rosenfeld, PJ Lewis, ML Rodriguez, B Torres, A Munoz, N Contreras, T Galvez, M Hess, D Cubillas, T Rams, I Slakter, JS Sorenson, JA Bruschi, PA Burke, K Schnipper, E Maranan, L Scolaro, M Riff, M Agresta, E Johansson, I Dedorsson, I Stenkula, S Hvarfner, C Carlsson, T Liljedahl, AM Fallstrom, S Jacobsson, E Soubrane, G Kuhn, D Oubraham, H Benelhani, A Kunsch, A Delhoste, B Ziverec, G Lasnier, M Lobes, LA Olsen, K Bahr, BJ Worstell, NT Wilcox, LA Wellman, LA Vagstad, G Steinberg, D Campbell, A Dreyer, R Williamson, B Johnson, M Crider, H Margherio, RR Williams, GA Zajechowski, M Stanley, C Kulak, M Streasick, P Szdlowski, L Falk, R Shoichet, S Regan, G Manatrey, P Cumming, K Koenig, F Benchaboune, M Mezmate, K Fontanay, S Meredith, T Binning, J Gualdoni, J Boyd, L Ort, E Barts, B Allen, R Dahl, J Holle, T Harvey, PT Kaus, L Leuschner, D Bolychuk, S Hewitt, I Menchini, U Bandello, F Virgili, G Lanzetta, P Ambesi, M Pirracchio, A Tedeschi, M Potter, MJ Sahota, B Hall, L Stur, M Lukas, J Tittl, M Docker, S Vogl, K Bressler, SB Bressler, NM Pieramici, DJ Manos, KS Cooper, R Denbow, RL Lowery, ER Phillips, DA Thibeault, SK Tian, Y Harnett, M Hawse, P Black, N Escartin, P Hartley, D Haworth, P Hecker, T Hiscock, D Jamali, F Maradan, N North, J Norton, B Stapleton-Hayes, T Taylor, R Huber, G Deslandes, JY Fsadni, M Hess, I de Pommerol, H Bobillier, A Reaves, A Banasik, S Koester, J Gray, T Truett, K Baker, J McAlister, L Birch, R Strong, A Azab, M Buskard, N Manjuris, U Hao, Y Mason, M McCurry, U Barbazetto, I Birngruber, R Bressler, SB Bressler, NM Donati, G Fish, GE Gragoudas, ES Harvey, P Kaiser, PK Koester, JM Lewis, H Lim, JI Ma, C Miller, JW Mones, J Murphy, SA Pieramici, DJ Potter, MJ Pournaras, CJ Schachat, AP Schmidt-Erfurth, U Singerman, L Slakter, JS Soubrane, S Strong, HA van den Berg, H Williams, GA Bressler, NM Manjuris, U Strong, HA Beck, RW Bird, AC Coscas, G Deutman, A Jampol, L Klein, R Maguire, M Deslandes, JY Huber, G Miller, JW Sickenberg, M Rosenfeld, P Stur, M Arceneaux, S Margherio, RP Staflin, P CA Verteporfin Photodynamic Therapy TI Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin - 1-year results of a randomized clinical trial - VIP report no. 1 SO OPHTHALMOLOGY LA English DT Article AB Objective: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, GA) can improve the chance of stabilizing or improving vision (<8 letter loss) safely in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. Design: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. Participants: One hundred twenty patients with subfoveal CNV caused by pathologic myopia with a greatest linear dimension no more than 5400 m and best-corrected visual acuity (Snellen equivalent) of approximately 20/100 or better. Intervention: Patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area; n = 81) or placebo (5% dextrose in water, n = 39) administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm was delivered at an intensity of 600 mW/cm(2) over 83 seconds to give a light dose of 50 J/cm(2) to a round spot size on the retina with a diameter of 1000 mum larger than the greatest linear dimension of the choroidal neovascular lesion. At follow-up examinations every 3 months, retreatment with either verteporfin or placebo (as assigned at baseline) was applied to areas of fluorescein leakage if present. Main Outcome Measures: The primary outcome was the proportion of eyes at the follow-up examination 12 months after study entry with fewer than eight letters (approximately 1.5 lines) of visual acuity lost, adhering to an intent-to-treat analysis. Results: At baseline, move than 90% of each group had evidence of classic CNV (regardless of whether occult CNV was present) and only 12 (15%) and 5 (13%) cases in the verteporfin and placebo groups, respectively, had occult CNV (regardless of whether classic CNV was present). Seventy-nine of the 81 verteporfin-treated patients (98%) compared with 36 of the 39 placebo-treated patients (92%) completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month 12 examination, 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters (P < 0.01), including 26 (32%) versus 6 (15%) improving at least five letters (1 line). Seventy (86%) of the verteporfin-treated patients compared with 26 (67%) of the placebo-treated patients lost fewer than 15 letters (P = 0.01), Few ocular or other systemic adverse events were associated with verteporfin therapy compared with placebo treatment. Conclusions: Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo, we recommend ophthalmologists consider verteporfin therapy for treatment of such patients. Ophthalmology 2001; 108:841-852 (C) 2001 by the American Academy of Ophthalmology. C1 CIBA Vis Corp, Med Affairs, Duluth, GA 30097 USA. Aberdeen Royal Infirm, Aberdeen, Scotland. Emory Eye Ctr, Atlanta, GA USA. Johns Hopkins Univ, Wilmer Ophthalmol Inst, Baltimore, MD 21218 USA. Inst Microcirugia Ocular Barcelona, Barcelona, Spain. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. Retina Associates, Cleveland, OH USA. Texas Retina Associates, Dallas, TX USA. Univ Essen Gesamthsch, Dept Ophthalmol, Essen, Germany. Hop Cantonal Univ Geneva, CH-1211 Geneva, Switzerland. Hop Ophtalm Univ, Lausanne, Switzerland. Royal Liverpool Univ Hosp, St Pauls Eye Unit, Liverpool, Merseyside, England. Univ So Calif, Doheny Eye Inst, Los Angeles, CA USA. Med Univ Lubeck, Klin Augenheilkunde, D-23538 Lubeck, Germany. Zweng Mem Retinal Res Fdn, Menlo Park, CA USA. Bascom Palmer Eye Inst, Miami, FL 33136 USA. Vetreous Retina Macula Consultants New York, New York, NY USA. Orebro Reg Sjukhuset, Ogonkliniken, Orebro, Sweden. Hop Intercommunal Creteil, Dept Ophthalmol, Paris, France. Retina Vitreous Consultants, Pittsburgh, PA USA. Retina NW PC, Portland, OR USA. Associated Retinal Consultants, Royal Oak, MI USA. Hop Bellevue, Serv Ophtalmol, St Etienne, France. Barnes Retina Inst, St Louis, MO USA. Univ Hlth Network, Toronto Western Div, Vis Sci Res Programme, Toronto, ON, Canada. Univ Udine, Dept Ophthalmol, I-33100 Udine, Italy. Univ British Columbia, Vancouver Hosp, Eye Care Ctr, Vancouver, BC V5Z 1M9, Canada. Allgemeines Krankenhaus Wien, Klin Augenheilkunde & Optometrie, Vienna, Austria. Wilmer Ophthalmol Inst, Baltimore, MD USA. CIBA Vis AG, Bulach, Switzerland. QLT Inc, Vancouver, BC, Canada. RP Bressler, NM (reprint author), CIBA Vis Corp, Med Affairs, 11460 Johns Creek Pkwy, Duluth, GA 30097 USA. RI Birngruber, Reginald/Q-2342-2016 NR 12 TC 299 Z9 310 U1 6 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2001 VL 108 IS 5 BP 841 EP 852 PG 12 WC Ophthalmology SC Ophthalmology GA 425WW UT WOS:000168315500020 ER PT J AU Scott, DL AF Scott, DL TI Pulmonary embolism after elective glenohumeral joint debridement SO ORTHOPEDICS LA English DT Article ID DEEP VENOUS THROMBOSIS; SUBCLAVIAN VEIN-THROMBOSIS; UPPER-EXTREMITY; THROMBOLYTIC THERAPY; RISK-FACTORS; AXILLARY; THROMBOEMBOLISM; US C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Scott, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, 149 13th St,MZ 1498000, Charlestown, MA 02129 USA. NR 51 TC 8 Z9 8 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD MAY PY 2001 VL 24 IS 5 BP 495 EP 497 PG 3 WC Orthopedics SC Orthopedics GA 433LX UT WOS:000168761800017 PM 11380001 ER PT J AU Merchant, SN Incesulu, A Glynn, RJ Nadol, JB AF Merchant, SN Incesulu, A Glynn, RJ Nadol, JB TI Histologic studies of the posterior stapediovestibular joint in otosclerosis SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT 133rd Annual Meeting of the American-Otological-Society CY MAY 12-13, 2000 CL ORLANDO, FLORIDA SP Amer Otol Soc DE otosclerosis; posterior stapediovestibular joint; ankylosis AB Objective: To determine the prevalence of ankylosis or otosclerosis at the posterior stapediovestibular joint (SVJ) in temporal bones with otosclerosis, with special reference to stapes surgery. Background: Long-term success of the laser stapedotomy minus prosthesis (STAMP) procedure, anterior crurotomy, and similar partial stapedectomy procedures depends on lack of ankylosis and lack of otosclerosis involving the posterior SVJ. Previous work has shown that the air-bone gap in otosclerosis correlates with narrowing and loss of the SVJ space. However, the prevalence and histologic features of otosclerotic involvement of the posterior SVJ space have not been well characterized. Methods: Histologic assessment of serial sections through the oval window niche in 140 temporal bones with otosclerosis that had been sectioned in the axial plane (age range 20-95 years, mean 68). Bones with stapes mobilization or stapedectomy were excluded. Results and Conclusions: Two of 140 bones had otosclerosis exclusively at the posterior SVJ. Of the remaining 138 bones, all of which had otosclerosis at the anterior SVJ, 82 bones also had otosclerosis at the posterior joint. Of the 56 bones without otosclerosis of the posterior joint, there was bony ankylosis of the posterior joint in 3 bones. Thus, 53 bones (38%) had neither ankylosis nor otosclerosis involving the posterior joint, and they would be potentially suitable for a laser STAMP or a similar procedure. There was no correlation between otosclerosis at the posterior SVJ and age, sex, or duration of conductive hearing loss. Otosclerosis at the posterior joint in one ear was significantly associated with its presence at the posterior joint in the opposite ear (p = 0.01). The audiogram could not be used to reliably predict otosclerotic involvement of the posterior SVJ or the degree of footplate pathologic changes, such as ankylosis. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA USA. Harvard Med Sch, Boston, MA USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R29 DC003657] NR 18 TC 12 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAY PY 2001 VL 22 IS 3 BP 305 EP 310 DI 10.1097/00129492-200105000-00006 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 428DP UT WOS:000168446300006 PM 11347631 ER PT J AU Casarett, D Karlawish, J Sankar, P Hirschman, KB Asch, DA AF Casarett, D Karlawish, J Sankar, P Hirschman, KB Asch, DA TI Obtaining informed consent for clinical pain research: patients' concerns and information needs SO PAIN LA English DT Article DE pain; research ethics; human subjects; informed consent ID QUALITY-OF-LIFE; AMBULATORY AIDS PATIENTS; CANCER PAIN; TRANSDERMAL FENTANYL; ORAL MORPHINE; BREAST-CANCER; BARRIERS; MANAGEMENT; QUESTIONNAIRE; CONVERSION AB Investigators who conduct clinical pain research are required to obtain voluntary informed consent from patients. However, little is known about what information patients expect when they decide whether to enroll in such studies. It is important that investigators understand these information needs so they can effectively and clearly describe the research risks and potential benefits that matter to potential subjects. By understanding these needs for information, investigators may also be better able to anticipate patients' concerns and to recruit subjects more efficiently. This study was designed to define information needs that patients have when they decide whether to participate in clinical pain research. This paper describes these information needs, and identifies clinical and demographic variables associated with specific needs. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Casarett, D (reprint author), Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 40 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 2001 VL 92 IS 1-2 BP 71 EP 79 DI 10.1016/S0304-3959(00)00473-5 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 433TU UT WOS:000168776500009 PM 11323128 ER PT J AU Oaklander, AL AF Oaklander, AL TI The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles SO PAIN LA English DT Article DE pain; pain mechanisms; neuropathic pain; PGP9.5; skin biopsy; herpes zoster ID ACUTE HERPES-ZOSTER; PAINFUL SENSORY NEUROPATHY; DORSAL HORN NEURONS; CUTANEOUS INNERVATION; FIBER DENSITY; SPINAL-CORD; HAIRY SKIN; DEGENERATION; MECHANISMS; INJURY AB The mechanisms of chronic neuropathic pain are not well understood. Postherpetic neuralgia (PHN), which occurs in some patients after shingles (herpes tester), was used to investigate the neural determinants of chronic pain. Skin biopsies were obtained from 38 adults with or without PHN at least 3 months after healing of shingles on the torso. Vertical sections were immunolabeled against PGP9.5, a pan-axonal marker, to measure the density of remaining nerve endings in skin previously affected by shingles. All axons that end in the epidermis are nociceptors, neurons that transmit pain messages. The densities ranged between 2 and 3976 neurites/mm(2) skin surface, but the overlap between subjects and without PHN was small. Of 19 subjects without PHN, 17 had more than 670 neurites/mm(2) skin surface area (mean +/- SEM = 1569 +/- 230), and 18 of 19 subjects with PHN had 640 or fewer neurites/mm(2) (mean +/- SEM = 367 +/- 92). PHN may be a 'phantom-skin' pain associated with loss of nociceptors. This threshold of approximately 650 neurites/mm(2) skin surface was not detected in previous studies that used summary statistics. It implies that the absence of pain after shingles may require the preservation of a minimum density of primary nociceptive neurons. and that the density of epidermal innervation may provide an objective correlate for the presence or absence of PHN pain. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02114 USA. Johns Hopkins Med Inst, Dept Neurol Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuropathol, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, 55 Fruit St,Clin 3, Boston, MA 02114 USA. NR 52 TC 121 Z9 128 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 2001 VL 92 IS 1-2 BP 139 EP 145 DI 10.1016/S0304-3959(00)00481-4 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 433TU UT WOS:000168776500016 PM 11323135 ER PT J AU Powers, PM Gerstle, R Lapey, A AF Powers, PM Gerstle, R Lapey, A TI Adolescents with cystic fibrosis: Family reports of adolescent health-related quality of life and forced expiratory volume in one second SO PEDIATRICS LA English DT Article DE cystic fibrosis; health-related quality of life; pediatrics; pulmonary function; forced expiratory volume in 1 second ID OF-LIFE; ADJUSTMENT; CHILDREN; PARENT AB Purpose. To assess the relationship between adolescent and parent reports of adolescent health-related quality of life (HRQL) and between adolescent pulmonary function (forced expiratory volume in 1 second as percent of predicted) and reporter perceptions of adolescent health. Methods. Twenty-four adolescents with cystic fibrosis (CF), their mothers, and their fathers completed the Child Health Questionnaire during routine CF clinic visits at 2 urban hospitals. Patients were between the ages of 11 and 18 years (mean age: 14.2 years) and were predominantly male (75%). The best measure of forced expiratory volume in 1 second as percent of predicted for the year of the study was also collected for each adolescent. Results. Adolescent pulmonary function was related to the perceived adolescent physical health scales. It was not, however, associated to perceptions of adolescent emotional, social, or behavioral HRQL by any of the 3 family reporters. Associations were found between adolescent pulmonary function and self-reports of general health (0.73), role/social limitations-physical (0.47), and bodily pain (0.42). Adolescent pulmonary function was related to mother reports of adolescent general health (0.73), role/social limitations-physical (0.73), bodily pain (0.55), and physical functioning (0.70). Father perceptions of adolescent health were associated to adolescent pulmonary function on general health (0.54), role/social limitations-physical (0.60), and physical functioning (0.64). Associations between adolescent and parent perceptions of adolescent HRQL were also health scale- specific. Mother and child reports of adolescent HRQL were related on adolescent behavior problems (0.71) and role/social limitations attributable to behavior (0.48), role/social limitations attributable to physical (0.62), bodily pain (0.69), physical functioning (0.69), family activities (0.45), and general health (0.66). Associations were found between father and adolescent reports on perceived adolescent behavior problems (0.66); self-esteem (0.65); and role/social limitations attributable to physical (0.49), general health (0.61), and perceived mental health (0.48). Conclusions. Results demonstrate the need to include multiple informants and comprehensive, multidimensional measures of HRQL, in addition to pulmonary function, when assessing health in adolescents with CF. C1 Tufts Univ, Dept Child Dev, Medford, MA 02155 USA. Baystate Med Ctr, Dept Pediat, Springfield, MA 01199 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Powers, PM (reprint author), Tufts Univ, Dept Child Dev, 105 Coll Ave, Medford, MA 02155 USA. FU NICHD NIH HHS [5732HD07415] NR 15 TC 17 Z9 17 U1 0 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2001 VL 107 IS 5 AR e70 DI 10.1542/peds.107.5.e70 PG 5 WC Pediatrics SC Pediatrics GA 427NA UT WOS:000168411100007 PM 11331720 ER PT J AU Zhang, KH Tarazi, FI Baldessarini, RJ AF Zhang, KH Tarazi, FI Baldessarini, RJ TI Nigrostriatal dopaminergic denervation enhances dopamine D-4 receptor binding in rat caudate-putamen SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE apomorphine; autoradiography; dopamine; D-2; D-4; 6-hydroxydopamine; receptors; rotational behavior ID MESSENGER-RNA LEVELS; DIFFERENTIAL REGULATION; BRAIN; EXPRESSION; SUBTYPES; NEUROLEPTICS; HALOPERIDOL; FOREBRAIN; STRIATUM; D-2-LIKE AB Radioligand binding to dopamine (DA) D-4 receptors was examined in adult rat forebrain 5 weeks after unilateral 6-hydroxydopamine (6-OHDA) lesioning of substantia nigra to remove ascending nigrostriatal dopaminergic projections. D-4 receptor binding was increased by up to 47% in denervated caudate-putamen (CPu) in rats that rotated away from the lesioned side with apomorphine challenge, with lesser changes in rats that failed to rotate with apomorphine. Functional significance of D-4 receptor upregulation induced by the lesions was investigated by examining behavioral effects of the highly selective D-4 agonist CP-226,269 and antagonist CP-293,019. Neither agent induced rotation at doses as high as 30 mg/kg ip. Pretreatment with the D-4 antagonist CP-293,019 did not affect rotation induced by either a D-1-like (SKF-38393) or D-2-like receptor (quinpirole) agonist. These findings provide the first evidence that Dq receptors can be upregulated by nigrostriatal dopaminergic denervation. They also suggest that, unlike D-1 and D-2 receptors, D-4 receptors do not play a pivotal role in rotational behavior in rats with unilateral dopaminergic lesions. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Zhang, KH (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, 115 Mill St, Belmont, MA USA. FU NIMH NIH HHS [MH-34006, MH-47370] NR 31 TC 9 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY-JUN PY 2001 VL 69 IS 1-2 BP 111 EP 116 DI 10.1016/S0091-3057(01)00499-3 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 444XJ UT WOS:000169425100014 PM 11420075 ER PT J AU Stavrev, P Stavreva, N Niemierko, A Goitein, M AF Stavrev, P Stavreva, N Niemierko, A Goitein, M TI Generalization of a model of tissue response to radiation based on the idea of functional subunits and binomial statistics SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID COMPLICATION PROBABILITY FACTOR; PARALLEL ARCHITECTURE; VOLUME; THERAPY; RADIOTHERAPY; OPTIMIZATION; IRRADIATION AB This work investigates the existing biological models describing the response of tumours and normal tissues to radiation, with the purpose of developing a general biological model of the response of tissue to radiation. Two different types of normal tissue behaviour have been postulated with respect to its response to radiation, namely critical element and critical volume behaviour. Based on the idea that an organ is composed of functional subunits, models have been developed describing these behaviours. However, these models describe the response of an individual, a particular patient or experimental animal, while the clinically or experimentally observed quantity is the population response. There is a need to extend the models to address the population response, based on the ideas we have about the individual response. We have attempted here to summarize and unify the existing individual models. Finally, the population models are investigated by fitting to pseudo-experimental sets of data and comparing them with each other in terms of goodness-of-fit and in terms of their power to recover the values of the population parameters. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Niemierko, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA 50628, CA 21239] NR 24 TC 30 Z9 30 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY PY 2001 VL 46 IS 5 BP 1501 EP 1518 DI 10.1088/0031-9155/46/5/312 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 436UA UT WOS:000168953200013 PM 11384067 ER PT J AU Figlewicz, DP Higgins, MS Ng-Evans, SB Havel, PJ AF Figlewicz, DP Higgins, MS Ng-Evans, SB Havel, PJ TI Leptin reverses sucrose-conditioned place preference in food-restricted rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE reward; dopamine; leptin; place preference ID BRAIN; REWARD; CHOLECYSTOKININ; REINFORCEMENT; MECHANISMS; INSULIN; COCAINE AB Previous studies have suggested that food restriction can modify performance in the conditioned place preference (CPP) paradigm. In the present study, we tested the hypotheses that food restriction would enhance the development of a CPP to low-calorie sucrose pellets and that peripheral leptin replacement in food-restricted animals would reverse this effect. Using a range of 45-mg sucrose pellets (0-15 pellets) as a reward, we observed that a significant place preference was conditioned in food-restricted, but not ad libitum-fed rats. This CPP was reversed either by treatment of food-restricted rats with the dopamine receptor antagonist ol-flupenthixol (200 mug/kg ip) during the training protocol or by chronic subcutaneous replacement of leptin (125 mug/kg/day) that attenuated the food restriction-induced decrease of circulating leptin. We conclude that dopaminergic signaling and the fall of plasma leptin concentrations contribute to the CPP of food-restricted rats. This finding suggests that in addition to metabolic adaptations, hypoleptinemia results in behavioral adaptations during states of energy deprivation. (C) 2001 Elsevier Science Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Metab Endocrinol 151,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK40963, DK-50129, DK-35747] NR 23 TC 81 Z9 82 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD MAY PY 2001 VL 73 IS 1-2 BP 229 EP 234 DI 10.1016/S0031-9384(01)00486-3 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 441PU UT WOS:000169239400029 PM 11399316 ER PT J AU Goodman, CM Steadman, AK Meade, RA Bodenheimer, C Thornby, J Netscher, DT AF Goodman, CM Steadman, AK Meade, RA Bodenheimer, C Thornby, J Netscher, DT TI Comparison of carpal canal pressure in paraplegic and nonparaplegic subjects: Clinical implications SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID TUNNEL SYNDROME; NERVE; COMPRESSION AB The purpose of this study was to evaluate the pressure within the carpal tunnel that was generated with certain tasks in paraplegic versus nonparaplegic subjects. Four groups of subjects were evaluated: 10 wrists in six paraplegic subjects with carpal tunnel syndrome, 11 wrists in six paraplegics without the syndrome, 12 wrists in nine nonparaplegics with the syndrome, and 17 wrists in 11 nonparaplegics without the syndrome. Carpel canal pressures were measured in the wrists in three positions (neutral, 45-degree flexion, 45-degree extension) and during two dynamic tasks [wheelchair propulsion and RAISE (relief of anatomic ischial skin embarrassment) maneuver]. External force resistors were placed over the carpal canal and correlated with interval tunnel pressures. At each wrist position, paraplegics with carpal tunnel syndrome consistently had higher carpal canal pressure than did the other groups at the corresponding wrist position; statistical significance was evident wit h regard to the neutral wrist position (p < 0.05). Within each group of subjects, wrist extension and wrist flexion produced a statistically significant increase in carpal canal pressure (p < 0.05), compared with the neutral wrist position. Dynamic tasks (wheelchair propulsion and the RAISE maneuver) significantly elevated the carpal canal pressure in paraplegics with carpal tunnel syndrome, compared with the other groups (p < 0.05). Lastly, there is a linear positive correlation between carpel canal pressure and external force resistance. C1 Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Plast Surg Serv, Houston, TX USA. Dept Vet Affairs Med Ctr, Dept Occupat Therapy Phys Med & Rehabil, Houston, TX USA. Dept Vet Affairs Med Ctr, Dept Stat, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 26 TC 13 Z9 14 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2001 VL 107 IS 6 BP 1464 EP 1471 DI 10.1097/00006534-200105000-00024 PG 8 WC Surgery SC Surgery GA 426JE UT WOS:000168345400024 PM 11335819 ER PT J AU Lee, WPA Rubin, JP Bourget, JL Cober, SR Randolph, MA Nielsen, GP Ierino, FL Sachs, DH AF Lee, WPA Rubin, JP Bourget, JL Cober, SR Randolph, MA Nielsen, GP Ierino, FL Sachs, DH TI Tolerance to limb tissue allografts between swine matched for major histocompatibility complex antigens SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LOW-DOSE CYCLOSPORINE; MINIATURE SWINE; RENAL-ALLOGRAFTS; CLASS-I; INDEFINITE SURVIVAL; TRANSPLANTATION; RATS; FK-506; LOCALIZATION; KIDNEY AB Transplantation of limb tissue allografts would greatly expand the realm of reconstructive surgery. Ho it ever, the toxicity of chronic immunosuppression has adversely tilted the risk-benefit balance for clinical transplant. In this study, a procedure was sought to achieve host tolerance to limb tissue allografts through matching of the major histocompatibility complex (MHC) antigens between donor and host swine using only a 12-day course of cyclosporine. Massachusetts General Hospital (MGH) miniature swine were used as a large animal model with defined MHC, and musculoskeletal grafts from the donor hind limb were transplanted heterotopically to the recipient femoral vessels. Allografts from MHC-mismatched donors treated with cyclosporine (n = 4) were rejected in less than 6 weeks by gross inspection and histologic sections. Allografts from MHC-matched, minor antigen mismatched donors not treated with cyclosporine (n = 4) were rejected between 9 and 12 weeks. Allografts from similarly matched donors treated with 12 days of cyclosporine (n = 7) showed no evidence of rejection until sacrifice between 25 and 47 weeks. Thus allograft tolerance was achieved between MHC-matched swine using a limited course of cyclosporine. Demonstration of limb tissue anograft survival in a large animal model without long-term immunosuppression represents an important step toward clinical transplantation. C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 453, Harvard Med Sch, Plast Surg Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 453, Harvard Med Sch, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 453, Harvard Med Sch, Plast Surg Res Lab, Boston, MA 02114 USA. NR 46 TC 41 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2001 VL 107 IS 6 BP 1482 EP 1490 DI 10.1097/00006534-200105000-00027 PG 9 WC Surgery SC Surgery GA 426JE UT WOS:000168345400027 PM 11335822 ER PT J AU Losken, A Swartz, MA Van den Abbeele, AD Jain, RK Slavin, SA AF Losken, A Swartz, MA Van den Abbeele, AD Jain, RK Slavin, SA TI A potential murine model for flap-related investigations SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID MYOCUTANEOUS FLAP; LATISSIMUS-DORSI; RAT; MUSCLE; VIABILITY C1 Emory Univ, Sch Med, Div Plast Surg, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Div Oncol Nucl Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Plast Surg, Boston, MA 02215 USA. RP Losken, A (reprint author), Emory Univ, Sch Med, Div Plast Surg, 1365B Clifton Rd NE, Atlanta, GA 30322 USA. RI Swartz, Melody/B-7633-2009; Swartz, Melody/F-9563-2011 NR 28 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2001 VL 107 IS 6 BP 1504 EP 1508 DI 10.1097/00006534-200105000-00032 PG 5 WC Surgery SC Surgery GA 426JE UT WOS:000168345400032 PM 11335827 ER PT J AU Yaremchuk, MJ AF Yaremchuk, MJ TI Infraorbital rim augmentation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID IMPLANTS; BLEPHAROPLASTY; SURGERY AB In patients with recessive infraorbital rims, alloplastic augmentation of the infraorbital rims makes the eyes appear less prominent and improves appearance. Ten patients (seven women and three men) with an average age of 30 years (range, 23 to 45 years) underwent augmentation of the infraorbital rim with alloplastic implants over a 9-year period. With an average follow-up of 3 years (range, 6 months to 6 years), reconstructions have remained stable and satisfactory, with no incidence of infection, infraorbital nerve damage, or palpebral fissure distortion. One patient underwent additional surgery to correct contour irregularities, and one patient requested implant removal 1 month after surgery. C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Plast Surg, Boston, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, WACC-453, Boston, MA 02114 USA. NR 20 TC 28 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2001 VL 107 IS 6 BP 1585 EP 1592 DI 10.1097/00006534-200105000-00047 PG 8 WC Surgery SC Surgery GA 426JE UT WOS:000168345400046 PM 11335841 ER PT J AU Cacciola, JS Alterman, AI McKay, JR Rutherford, MJ AF Cacciola, JS Alterman, AI McKay, JR Rutherford, MJ TI Psychiatric comorbidity in patients with substance use disorders: Do not forget Axis II disorders SO PSYCHIATRIC ANNALS LA English DT Article ID ANTISOCIAL PERSONALITY-DISORDER; METHADONE-MAINTENANCE PATIENTS; POSTTRAUMATIC-STRESS-DISORDER; OPIATE-DEPENDENT PATIENTS; PLACEBO-CONTROLLED TRIAL; SEEKING COCAINE ABUSERS; FOLLOW-UP; IMIPRAMINE TREATMENT; DRUG-ABUSE; DIAGNOSIS C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Washington, Inst Alcohol & Drug Abuse, Woodinville, WA USA. RP Cacciola, JS (reprint author), PENN TRC, 3900 Chestnut St, Philadelphia, PA 19104 USA. NR 59 TC 24 Z9 24 U1 2 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD MAY PY 2001 VL 31 IS 5 BP 321 EP 331 PG 11 WC Psychiatry SC Psychiatry GA 431GQ UT WOS:000168623800006 ER PT J AU Reno, R AF Reno, R TI Maintaining quality of in a comprehensive dual diagnosis treatment program SO PSYCHIATRIC SERVICES LA English DT Article ID SUBSTANCE AB This paper describes how a large, multifaceted dual diagnosis treatment program has attempted to preserve its mission through termination of or changes in the nature of resident research projects. Research reports, because of their focus on specific treatment components, often fail to capture the essence of the larger treatment contexts from which they emanate, Although host programs derive benefits fi-om research projects, enhancements are often temporary and difficult to sustain. Programs are thus challenged to respond to resource losses creatively. The author discusses adaptations to losses in the areas of case management, behavioral skills training, an incentive system,, money management, and continuity of care. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dual Diag Treatment Program Day Hosp, Los Angeles, CA 90073 USA. RP Reno, R (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat, 11301 Wilshire Blvd,205C, Los Angeles, CA 90073 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD MAY PY 2001 VL 52 IS 5 BP 673 EP 675 DI 10.1176/appi.ps.52.5.673 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 432GB UT WOS:000168682900018 PM 11331804 ER PT J AU Shores, MM Pascualy, M Lewis, NL Flatness, D Veith, RC AF Shores, MM Pascualy, M Lewis, NL Flatness, D Veith, RC TI Short-term sertraline treatment suppresses sympathetic nervous system activity in healthy human subjects SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE sympathetic nervous system; selective serotonin reuptake inhibitor; sertraline; norepinephrine kinetics; norepinephrine; epinephrine ID BLOOD-PRESSURE; NOREPINEPHRINE; DEPRESSION; INHIBITION; CLEARANCE; RESPONSES; SEROTONIN; RAT AB Increased sympathetic nervous system (SNS) activity has been associated with stress, major depression, aging, and several medical conditions. This study assessed the effect of the selective serotonin reuptake inhibitor (SSRI), sertraline, on sympathetic nervous system (SNS) activity in healthy subjects. Twelve healthy volunteers participated in a double-blind, placebo-controlled, norepinephrine (NE) kinetic study, in which the effects of sertraline on SNS activity were ascertained by determining NE plasma concentrations and NE plasma appearance rates and clearance rates in sertraline or placebo conditions. Subjects received 50 mg of sertraline or placebo for two days and then one week later underwent the same protocol with the other drug. By single compartmental analysis, plasma NE appearance rates were significantly lower in the sertraline compared to the placebo condition (0.26+/-0.10 vs 0.40+/-0.23 mug/m(2)/min; P=0.04). Our study found that the net effect of short-term SSRI treatment is an apparent suppression of SNS activity as indicated by a decreased plasma NE appearance rate in the sertraline condition. If this preliminary finding can be extended to long-term treatment of patients, this could have significant therapeutic relevance for treating depression in elderly patients or those with cardiac disease, in which elevated SNS activity may exacerbate underlying medical conditions. Published by Elsevier Science Ltd. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Shores, MM (reprint author), VA Puget Sound Hlth Care Syst, 182B,S Columbian Way, Seattle, WA 98108 USA. NR 14 TC 50 Z9 53 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD MAY PY 2001 VL 26 IS 4 BP 433 EP 439 DI 10.1016/S0306-4530(01)00002-6 PG 7 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 420QR UT WOS:000168016100007 PM 11259862 ER PT J AU Spillmann, MK Van der Does, AJW Rankin, MA Vuolo, RD Alpert, JE Nierenberg, AA Rosenbaum, JF Hayden, D Schoenfeld, D Fava, M AF Spillmann, MK Van der Does, AJW Rankin, MA Vuolo, RD Alpert, JE Nierenberg, AA Rosenbaum, JF Hayden, D Schoenfeld, D Fava, M TI Tryptophan depletion in SSRi-recovered depressed outpatients SO PSYCHOPHARMACOLOGY LA English DT Article DE tryptophan depletion; depression; antidepressant; remission; mood effect ID RAPID DEPLETION; ANTIDEPRESSANT ACTION; SEROTONIN FUNCTION; RELAPSE; FLUOXETINE; MECHANISM; CHALLENGE; SCALE AB Rationale: Recently, a number of studies have challenged the finding that acute tryptophan depletion (TD) increases depressive symptoms in medicated, formerly depressed patients. The present study examined the effects of acute nutritional TD on remitted depressed patients currently treated with selective serotonin reuptake inhibitors. In an attempt to clarify conflicting earlier findings, the effects of a number of clinical variables on outcome were also investigated. Methods: Ten patients underwent TD in a double-blind, controlled, balanced crossover fashion. The control session followed the procedure of Krahn et al. (1996 Neuropsychopharmacology 15:325-328). Sessions were 5-8 days apart. Results: TD was significantly related to increased scores on clinician-rated depression and anxiety scales, and on self-rated depression, anxiety, and somatic symptoms. The control challenge had no effect, despite the fact that the reductions in plasma tryptophan during the central session were unexpectedly high. Some evidence was found for a threshold in the relationship between reduction of plasma tryptophan and mood response. Conclusions: The mood effect of TD in medicated, formerly depressed patients was confirmed. A threshold may exist for mood effects following TD, implying that recent negative findings may have been caused by insufficient depletion. No other predicting or mediating factors were identified, although the variable "history of response pattern, to medication" deserves further study. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, WAC 812, Boston, MA 02114 USA. Leiden Univ, Dept Psychol, Leiden, Netherlands. Leiden Univ, Dept Psychiat, Leiden, Netherlands. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, WAC 812, 15 Parkman St, Boston, MA 02114 USA. RI Van der Does, Willem/B-1465-2008; OI Van der Does, Willem/0000-0002-9753-2454; Alpert, Jonathan/0000-0002-4332-908X FU NCRR NIH HHS [M01-RR0-1066] NR 21 TC 59 Z9 60 U1 3 U2 6 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2001 VL 155 IS 2 BP 123 EP 127 DI 10.1007/s002130000669 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 433UK UT WOS:000168778000002 PM 11400999 ER PT J AU Weinstock, L Cohen, LS Bailey, JW Blatman, R Rosenbaum, JF AF Weinstock, L Cohen, LS Bailey, JW Blatman, R Rosenbaum, JF TI Obstetrical and neonatal outcome following clonazepam use during pregnancy: A case series SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE clonazepam; pregnancy; benzodiazepines; prenatal exposure; obstetrical outcome; neonatal outcome ID PANIC-DISORDER; DOUBLE-BLIND; LONGITUDINAL COURSE; MATERNAL ANXIETY; ALPRAZOLAM; PLACEBO; AGORAPHOBIA; DIAZEPAM; ATTACKS; EFFICACY AB Background: Given the high prevalence of panic disorder in women, treatment decisions are frequently made regarding the use of anti-panic medications during the childbearing years and during pregnancy. The objective of this case series was to evaluate obstetric and neonatal outcome associated with treatment with clonazepam during pregnancy. Methods: Subjects were 38 women with histories of panic disorder who used clonazepam during pregnancy. Information regarding the amount and duration of clonazepam use during pregnancy was obtained. Obstetrical records describing pregnancy, labor and delivery and infant Apgar scores were obtained for all subjects. Neonatal nursery records were obtained for 27 subjects. Results: Maternal outcome assessed by obstetrical records and acute neonatal outcome assessed by Apgar scores were positive. Based on neonatal records, there were no cases of orofacial anomalies, neonatal apnea, benzodiazepine withdrawal syndromes, or temperature or other autonomic dysregulation. In 2 infants born to the same mother, use of clonazepam and imipramine at the time of delivery was associated with transient neonatal distress. Conclusion: Clonazepam use during pregnancy did not appear to be directly related to any obstetric complications during pregnancy, labor, or delivery. There was no evidence of neonatal toxicity or withdrawal syndromes in babies born to mothers who took clonazepam during pregnancy. Absence of serious maternal or neonatal compromise following clonazepam use during pregnancy in these mothers and infants is somewhat reassuring. One case of hypotonia and 1 case of respiratory distress in babies who were exposed to clonazepam in combination with imipramine at the time of delivery may suggest that coadministration of benzodiazepines with other psychotropic medications may require close neonatal observation. Copyright (C) 2001 S. Karger AG.,Basel C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Perinatal & Reprod Psychiat Clin Res Program, Ctr Womens Mental Hlth,Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Maternal & Fetal Med Obstet & Gynecol, Boston, MA 02114 USA. RP Cohen, LS (reprint author), Massachusetts Gen Hosp, Psychopharmacol Unit, 15 Parkman St,WACC 815, Boston, MA 02114 USA. NR 54 TC 11 Z9 11 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD MAY-JUN PY 2001 VL 70 IS 3 BP 158 EP 162 DI 10.1159/000056242 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 430EP UT WOS:000168561600007 PM 11340418 ER PT J AU O'Neill, MJ Rafferty, EA Lee, SI Arellano, RS Gervais, DA Hahn, PF Yoder, IC Mueller, PR AF O'Neill, MJ Rafferty, EA Lee, SI Arellano, RS Gervais, DA Hahn, PF Yoder, IC Mueller, PR TI Transvaginal interventional procedures: Aspiration, biopsy, and catheter drainage SO RADIOGRAPHICS LA English DT Article DE ovary, cysts; pelvic organs, abscess; pelvic organs, interventional procedures ID FINE-NEEDLE ASPIRATION; SONOGRAPHICALLY GUIDED ASPIRATION; OVARIAN CYSTS; PELVIC ABSCESSES; PERCUTANEOUS DRAINAGE; FLUID COLLECTIONS; TUBOOVARIAN ABSCESSES; MANAGEMENT; PUNCTURE; CYTOLOGY AB Transvaginal ultrasonographically (US) guided procedures are simple and safe and often represent the only means of access to pelvic disease. Aspiration of cystic pelvic masses and core biopsy of solid pelvic masses can be easily performed by using the transvaginal route, an endoluminal US transducer, and a needle guide. Because of concerns about false-negative diagnosis and potential tumor seeding with biopsy of primary ovarian cystic lesions, the indications for transvaginal aspiration and biopsy of ovarian and adnexal lesions are predominantly therapeutic. Similarly, using an endoluminal probe with modification of the guide, one can also perform safe and effective trocar catheter drainage of pelvic abscesses via the transvaginal route. The transvaginal route is ideally suited to pelvic abscess drainage because of the proximity of the vaginal fornices to most pelvic fluid collections. The transvaginal route has the disadvantage of being semisterile; because of the risk of superinfecting previously noninfected pelvic pathologic conditions, the transvaginal approach should be used only for solid lesions or cystic lesions that can be completely aspirated. Familiarity with the transvaginal route of access is crucial for adequate treatment of many gynecologic and nongynecologic pelvic pathologic conditions. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP O'Neill, MJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 33 TC 16 Z9 18 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2001 VL 21 IS 3 BP 657 EP 672 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 471KL UT WOS:000170928500010 PM 11353114 ER PT J AU Gervais, DA Fernandez-del Castillo, C O'Neill, MJ Hahn, PF Mueller, PR AF Gervais, DA Fernandez-del Castillo, C O'Neill, MJ Hahn, PF Mueller, PR TI Complications after pancreatoduodenectomy: Imaging and imaging-guided interventional procedures SO RADIOGRAPHICS LA English DT Article DE abdomen, abscess; pancreas; pancreas; pancreas, interventional procedures; pancreas, neoplasms; pancreas, surgery; pancreas ID 250 ABDOMINAL ABSCESSES; CONSECUTIVE PANCREATICODUODENECTOMIES; PERCUTANEOUS DRAINAGE; ACUTE-PANCREATITIS; FLUID COLLECTIONS; WHIPPLE PROCEDURE; PELVIC ABSCESSES; MORTALITY; MANAGEMENT; MORBIDITY AB Over the past decade, performance of the Whipple procedure, or pancreatoduodenectomy, to treat both malignant and benign disease has increased. This increase is in large part due to the decreasing perioperative mortality rate, which is down from historic highs of 25% to the 1.0%-1.5% now achieved in large centers. Although advances in surgical management have improved the outlook for patients undergoing pancreatoduodenectomy, the improving mortality rate is also in part attributed to improvements over the past 2 decades in cross-sectional imaging and imaging-guided interventional procedures. Although the mortality rates have improved, the morbidity, or rate of complications, has remained relatively constant. Contributions by radiologists in both diagnosis and treatment of complications are crucial in certain patients with postpancreatoduodenectomy abdominal abscesses, bilomas, liver abscess, and biliary obstruction. Familiarity with normal variations in the postoperative appearance of the upper abdomen, awareness of pitfalls in interpretation, and knowledge of the available imaging-guided interventions will facilitate recognition of postpancreatoduodenectomy complications and allow prompt triage of patients to imaging-guided interventions. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 35 TC 32 Z9 33 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2001 VL 21 IS 3 BP 673 EP 690 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 471KL UT WOS:000170928500011 PM 11353115 ER PT J AU Weissleder, R Mahmood, U AF Weissleder, R Mahmood, U TI Molecular imaging SO RADIOLOGY LA English DT Review DE molecular analysis; radiology and radiologists, research; review ID POSITRON-EMISSION-TOMOGRAPHY; RAY COMPUTED-TOMOGRAPHY; OPTICAL COHERENCE TOMOGRAPHY; REPORTER GENE-EXPRESSION; KINASE ENZYME-ACTIVITY; IRON-OXIDE PARTICLES; IN-VIVO; TUMOR ANGIOGENESIS; LIVING ANIMALS; TRANSGENE EXPRESSION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ctr Mol Imaging Res, Bldg 149,Rm 5403, Charlestown, MA 02129 USA. NR 141 TC 958 Z9 1071 U1 24 U2 244 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2001 VL 219 IS 2 BP 316 EP 333 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 425WF UT WOS:000168314100003 PM 11323453 ER PT J AU Kohane, DS Lu, NT Cairns, BE Berde, CB AF Kohane, DS Lu, NT Cairns, BE Berde, CB TI Effects of adrenergic agonists and antagonists on tetrodotoxin-induced nerve block SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article DE adrenergic; local anesthetic; peripheral nerve; sciatic; tetrodotoxin ID LOCAL-ANESTHETIC ACTIVITY; IN-VIVO; BLOOD-FLOW; RAT; CLONIDINE; EPINEPHRINE; BUPIVACAINE; LIDOCAINE; MORPHINE AB Background and Objectives: The relative contributions of alpha (1)-, alpha (2)-, and beta -adrenergic receptors to adrenergic agonists' prolongation of nerve block by tetrodotoxin (TTX) are unknown. We investigated which receptor agonists prolong TTX block, and whether delayed injection of antagonists can interrupt prolonged blocks after coinjection of TTX and agonists. Methods: Rats received percutaneous sciatic nerve block with 120 mu mol/L TTX with and without adrenergic agonists and antagonists. Block duration was assessed by a modified hot-plate test. Functional deficits in the uninjected leg were used to assess systemic distribution of TTX. Data were expressed as medians with 25th and 75th percentiles. Results: Coinjection of 5.5 mu mol/L phenylephrine (al-specific). 10 mu mol/L clonidine (alpha (2)-specific), and 1.1 mu mol/L epinephrine (mixed alpha- and beta -agonist) prolonged TTX nerve block, but 5.5 mu mol/L isoproterenol (mixed P-agonist) did not. Yohimbine inhibited TTX block prolongation by clonidine (median inhibitory concentrations, IC50 = 130 nmol/L); phentolamine similarly inhibited epinephrine (IC50 = 45 nmol/L). Adrenergic antagonists did not inhibit the prolongation of TTX block by agonists when injected 3 or 6 hours after the initial block. Subcutaneous injection of adrenergic agonists at a remote site did not prolong TTX block, except for a modest prolongation by clonidine. Conclusions: TTX block can be prolonged by alpha (1)- and alpha (2)-, but not beta -adrenergic agonists via locally mediated events of relatively brief duration. Delayed injection of adrenergic antagonists does not interrupt the prolonged blocks produced by coinjection of TTX and adrenergic agonists unless administered soon after block is established. C1 Childrens Hosp, Dept Anesthesia, Pain Treatment Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Berde, CB (reprint author), Childrens Hosp, Dept Anesthesia, Pain Treatment Serv, 333 Longwood Ave,5th Floor, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM 684-01] NR 30 TC 12 Z9 13 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAY-JUN PY 2001 VL 26 IS 3 BP 239 EP 245 DI 10.1053/rapm.2001.23215 PG 7 WC Anesthesiology SC Anesthesiology GA 434YK UT WOS:000168843300007 PM 11359223 ER PT J AU Puglielli, L Kovacs, DM AF Puglielli, L Kovacs, DM TI Alzheimer disease: 100 years later SO REVISTA MEDICA DE CHILE LA English DT Article DE Alzheimer disease; amyloid beta-protein; genetics, biochemical; molecular biology ID AMYLOID PRECURSOR PROTEIN; RECEPTOR-RELATED PROTEIN; HUMAN APOLIPOPROTEIN-E; BETA-SECRETASE; CYTOPLASMIC DOMAIN; MICROGLIAL CELLS; MOUSE MODEL; PEPTIDE; PRESENILINS; DEPOSITION AB Almost 100 years since the first clinical report of a case of Alzheimer disease (AD), three early-onset and two late-onset AD genes have been identified. While rare mutations in the early-onset genes (amyloid precursor protein, and presenilins 1 and 2) lead to increased generation of specific forms of the amyloid beta protein (A,beta), common polymorphisms in the late-onset genes (apolipoprotein E and alpha (2)-macroglobulin) are thought to alter the clearance and degradation of A,beta in brain. Although definite proof for a direct link between altered A beta generation/clearance and neurodegeneration has not yet been attained, mechanism-based approaches for the therapeutic treatment of AD based on lowering levels of the potentially pathogenic A beta are currently underway. The recent discovery of the enzymes (secretases) responsible for generating A beta have paved the way for the development of such drugs and increase the prospects for successful therapeutic intervention to arrest AD neuropathogenesis (Rev Med Chile 2001; 129: 569-75). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, Charlestown, MA USA. RP Kovacs, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, Bldg 149,13th St, Charlestown, MA USA. NR 43 TC 2 Z9 2 U1 0 U2 1 PU SOC MEDICA SANTIAGO PI SANTIAGO 9 PA BERNARDA MORIN 488 PROVIDENCIA, CASILLA 168 CORREO 55, SANTIAGO 9, CHILE SN 0034-9887 J9 REV MED CHILE JI Rev. Medica Chile PD MAY PY 2001 VL 129 IS 5 BP 569 EP 575 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 449DU UT WOS:000169669700015 PM 11464541 ER PT J AU Zhang, ZX Bridges, SL AF Zhang, ZX Bridges, SL TI Pathogenesis of rheumatoid arthritis - Role of B lymphocytes SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID CARTILAGE PROTEOGLYCAN AGGRECAN; GERMINAL-CENTERS; SOMATIC MUTATION; SYNOVIAL TISSUE; II COLLAGEN; MOLECULAR ANALYSIS; T-CELL; ARTICULAR-CARTILAGE; V(D)J RECOMBINATION; KERATAN SULFATE C1 Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Div Dev & Clin Immunol, Birmingham, AL 35294 USA. Univ Alabama, Arthrit Clin Intervent Program, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Bridges, SL (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, 415 Lyons Harrison Res Bldg, Birmingham, AL 35294 USA. NR 136 TC 35 Z9 49 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD MAY PY 2001 VL 27 IS 2 BP 335 EP 353 DI 10.1016/S0889-857X(05)70205-2 PG 19 WC Rheumatology SC Rheumatology GA 436WB UT WOS:000168957900005 PM 11396096 ER PT J AU Liu, H Jensen, L Hansen, S Petersen, SV Takahashi, K Ezekowitz, AB Hansen, FD Jensenius, JC Thiel, S AF Liu, H Jensen, L Hansen, S Petersen, SV Takahashi, K Ezekowitz, AB Hansen, FD Jensenius, JC Thiel, S TI Characterization and quantification of mouse mannan-binding lectins (MBL-A and MBL-C) and study of acute phase responses SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATES COMPLEMENT; SERINE-PROTEASE; SERUM; ASSOCIATION; GENE; PURIFICATION; MUTATIONS; PROTEINS; PATHWAY; DEFECT AB Rat monoclonal antibodies (MoAbs) against mouse mannan-binding lectin (MBL)-A and MBL-C were generated and assays for MBL-A and MBL-C were constructed. This allowed for the quantitative analysis of both proteins for the first time. Previously only MBL-A has been quantified using less standardized methods. In a mouse serum pool the concentrations were now determined at 7.5 mug MBL-A and 45 mug MBL-C per ml. On gel permeation chromatography of mouse serum, MBL-A eluted corresponding to a M-r of 850 kDa whereas the majority of MBL-C eluted corresponding to a M-r of 950 kDa. On sucrose density gradient centrifugation the sedimentation velocities of MBL-A and MBL-C were estimated at 7.3 S and 10.8 S, respectively, The MBL-A and MBL-C levels in 10 laboratory mice strains were compared and found to vary between 4 mug/ml to 12 mug/ml, and 16 mug/ml to 118 mug/ml, respectively. After the induction of acute phase responses by intraperitoneal injection of either casein or lipopolysaccharide (LPS), MBL-A was found to increase approximately two-fold, with a maximum after 32 h, while MBL-C did not increase significantly. In comparison, serum amyloid A component (SAA) peaked at 15 h with an approximate 100-fold increase. C1 Aarhus Univ, Dept Med Microbiol & Immunol, DK-8000 Aarhus, Denmark. Univ So Denmark, Inst Med Biol, Odense, Denmark. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thiel, S (reprint author), Aarhus Univ, Dept Med Microbiol & Immunol, Bartholin Bldg, DK-8000 Aarhus, Denmark. OI Hansen, Soren/0000-0002-8186-4630 NR 25 TC 67 Z9 71 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2001 VL 53 IS 5 BP 489 EP 497 DI 10.1046/j.1365-3083.2001.00908.x PG 9 WC Immunology SC Immunology GA 426YR UT WOS:000168378100009 PM 11309157 ER PT J AU Z'graggen, K Centeno, BA Fernandez-del Castillo, C Jimenez, RE Werner, J Warshaw, AL AF Z'graggen, K Centeno, BA Fernandez-del Castillo, C Jimenez, RE Werner, J Warshaw, AL TI Biological implications of tumor cells in blood and bone marrow of pancreatic cancer patients SO SURGERY LA English DT Article ID POLYMERASE CHAIN-REACTION; REVERSE-TRANSCRIPTASE; COLORECTAL-CANCER; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; PERITONEAL CYTOLOGY; PERIPHERAL-BLOOD; MESSENGER-RNA; IMMUNOCYTOCHEMICAL DETECTION; HEPATOCELLULAR-CARCINOMA AB Background. Patients with pancreatic cancer often have tumor recurrence despite curative resection. Cancer cells detected in blood or bone marrow at the time of diagnosis may relate to tumor stage and to prognosis. Recent research emphasis has centered on tumor cells in bone marrow aspirates, but whether these represent early micrometastases or blood-borne cells in transit is unknown. Patients and Methods. We developed a specific immunocytochemical assay that evaluated more than 5.3 x 10(6) extracted mononuclear cells pm sample of blood and bone marrow and that could identify a single tumor cell in that population. The assay was applied to samples of blood and bone marrow from 105 patients with pancreatic cancer and 66 controls. The prevalence of isolated tumor cells was compared with Union Internationale Contre Ie Cancer (UICC) stage. ii multivariate Cox regression analysis for survival was performed. Results. Pancreatic cancer cells were detected in 26% of blood samples and in 24% of bone marrow specimens. Specificity for cancer was 96%. The prevalence of isolated tumor cells in patients with proven resectable cancer was 9% in blood and 13% in bone marrow. The prevalence increased with UICC tumor stage in blood ( P =.04) but not In bone marrow (P =.52) and correlated in blood with resectability (P =.02), progression of disease (P=.08), and peritoneal dissemination (P=.003). While survival correlated significantly with tumor stage (P <.001) and isolated tumor cells in blood correlated with tumor stage, the finding of cancer cells in blood or bone marrow, or both, was not independently associated with survival in patients with pancreatic cancer. Conclusions, Isolated tumor cells in blood but not bone marrow reflect the stage of growth and spread of pancreatic cancer, particularly in the peritoneal cavity. The findings are consistent with cells in bone marrow aspirates being in transit, not implanted. These disseminated cancer cells may be the consequence, rather than the cause, of progression. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,White 506, Boston, MA 02114 USA. NR 49 TC 54 Z9 55 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2001 VL 129 IS 5 BP 537 EP 546 DI 10.1067/msy.2001.113819 PG 10 WC Surgery SC Surgery GA 428GX UT WOS:000168454300004 PM 11331445 ER PT J AU Marlar, RA AF Marlar, RA TI Commentary - The protein C system - How complex is it? SO THROMBOSIS AND HAEMOSTASIS LA English DT Editorial Material ID C4B-BINDING PROTEIN; INHIBITION C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80220 USA. RP Marlar, RA (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. NR 9 TC 2 Z9 3 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAY PY 2001 VL 85 IS 5 BP 756 EP 757 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 433YJ UT WOS:000168788000001 PM 11372662 ER PT J AU Allan, JS Rose, GA Choo, JK Arn, JS Vesga, L Mawulawde, K Slisz, JK Allison, K Madsen, JC AF Allan, JS Rose, GA Choo, JK Arn, JS Vesga, L Mawulawde, K Slisz, JK Allison, K Madsen, JC TI Morphometric analysis of miniature swine hearts as potential human xenografts SO XENOTRANSPLANTATION LA English DT Article DE echocardiography; heart; morphometry; swine; xenotransplantation ID MAJOR HISTOCOMPATIBILITY COMPLEX; TRANSPLANTATION AB Miniature swine are considered to be potential donors for clinical cardiac transplantation. However, it is unclear how an appropriately sized porcine donor will be selected for a particular human recipient. To address this issue, we performed a morphometric study of the swine heart using transthoracic echocardiography (n=26) to determine the diameters of the aortic annulus and root, pulmonary artery annulus, and mitral valve annulus. We also obtained direct ex vivo measurements of swine heart weight and linear dimensions (n=71). Relationships between a swine's height, weight, length, chest circumference and these internal and external cardiac dimensions are described. The strongest correlations were found between a pig's body length and its aortic annulus and root diameters (r-values=0.97). These relationships are accurately described by univariate linear regression models. By cross-relating our morphometric measurements of aortic annulus diameter in the miniature swine with normative human data, we were able to develop a nomogram, relating swine length and human height, which predicts which miniature swine would donate the best size-matched heart for a particular human recipient. C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. NR 7 TC 13 Z9 16 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2001 VL 8 IS 2 BP 90 EP 93 DI 10.1034/j.1399-3089.2001.00176.x PG 4 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 435NP UT WOS:000168887800003 PM 11328578 ER PT J AU Kim, JW Chang, TS Lee, JE Huh, SH Yeon, SW Yang, WS Joe, CO Mook-Jung, I Tanzi, RE Kim, TW Choi, EJ AF Kim, JW Chang, TS Lee, JE Huh, SH Yeon, SW Yang, WS Joe, CO Mook-Jung, I Tanzi, RE Kim, TW Choi, EJ TI Negative regulation of the SAPK/JNK signaling pathway by presenilin 1 SO JOURNAL OF CELL BIOLOGY LA English DT Article DE apoptosis; c-Jun NH2-terminal kinase; presenilin 1; gamma-secretase; stress-activated protein kinase ID FAMILIAL ALZHEIMERS-DISEASE; AMYLOID PRECURSOR PROTEIN; MAP KINASES; MISSENSE MUTATIONS; INDUCED APOPTOSIS; MAMMALIAN-CELLS; GENE; NOTCH; JNK; STRESS AB Presenilin 1 (PS1) plays a pivotal role in Notch signaling and the intracellular metabolism of the amyloid beta -protein, To understand intracellular signaling events downstream of PSI, we investigated in this study the action of PS1 on mitogen-activated protein kinase pathways. Overexpressed PS1 suppressed the stress-induced stimulation of stress-activated protein kinase (SAPK)/c-Jun NH2-terminal kinase (JNK) in human embryonic kidney 293 cells. Interestingly, two functionally inactive PSI mutants, PS1(D257A) and PS1(D385A), failed to inhibit UV-stimulated SAPK/ JNK. Furthermore, H2O2- or UV-stimulated SAPK activity was higher in mouse embryonic fibroblast (MEF) cells from PS1-null mice than in MEF cells from PS+/+ mice. MEFPS1(-/-) cells were more sensitive to the H2O2-induced apoptosis than MEFPS1(+/+) cells. Ectopic expression of PS1 in MEFPS1(-/-) cells suppressed H2O2-stimulated SAPK/JNK activity and apoptotic cell death. Together, our data suggest that PS1 inhibits the stress-activated signaling by suppressing the SAPK/ JNK pathway. C1 Korea Univ, Grad Sch Biotechnol, Natl Creat Res Initiat Ctr Cell Death, Seoul 136701, South Korea. Ajou Univ, Sch Med, Brain Dis Res Ctr, Suwon, Kyongki Do, South Korea. Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Choi, EJ (reprint author), Korea Univ, Grad Sch Biotechnol, Natl Creat Res Initiat Ctr Cell Death, Seoul 136701, South Korea. RI KIM, JIN WOO/C-1655-2011; Joe, Cheol O/C-1917-2011; Mook, Inhee/J-2754-2012 OI KIM, JIN WOO/0000-0003-0767-1918; NR 48 TC 21 Z9 21 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 30 PY 2001 VL 153 IS 3 BP 457 EP 463 DI 10.1083/jcb.153.3.457 PG 7 WC Cell Biology SC Cell Biology GA 428VB UT WOS:000168481400003 PM 11331298 ER PT J AU McGibbon, CA Palmer, T Goldvasser, D Krebs, DE AF McGibbon, CA Palmer, T Goldvasser, D Krebs, DE TI Kalman filter detection of blinks in video-oculography: applications for VVOR measurement during locomotion SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE video-based eye kinematics; blink removal; visual vestibulo-ocular reflex; VVOR gain and phase; bilateral vestibular hypofunction; locomotion ID VESTIBULOOCULAR REFLEX; TRAJECTORY ANALYSIS; EYE-MOVEMENT; REHABILITATION; SACCADES AB A Kalman filter algorithm was implemented for automatic detection of blink artifacts in video-oculography (VOG) data, and a cubic spline used to patch the eliminated data. The algorithm was tested by randomly introducing artificial blinks into eye movement data and computing the errors introduced by the patches. We also computed visual vestibule-ocular reflex (VVOR) gain and phase in healthy and vestibulopathic subjects during a locomotor task, before and after blink removal, to demonstrate the interpretive importance of eliminating blink artifacts. The error introduced by the patched data was small (0.50 +/- 0.32 degrees) and within the resolution of head angle measurements. Comparison of gain and phase shift before and after removing blinks revealed that even when calculated values are within expected limits, coherence of the VVOR signal was significantly (p = 0.003) lower prior to blink removal (0.51 +/- 0.37) compared to that after blink removal (0.92 +/- 0.08). Comparison of VVOR calculations between healthy and vestibulopathic subjects (after removal of blinks) revealed that vestibulopathic subjects had significantly decreased gains (p = 0.018) and increased phase shifts (p = 0.009). these results agree with data reported in literature. We conclude that the Kalman filter detection and cubic spline patching algorithms are useful tools for VOG and should enable reliable VVOR measurements during unconstrained, ecologically meaningful locomotor activities. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. MGH Inst Hlth Profess, Boston, MA USA. Harvard Univ, Sch Med, Dept Orthopaed, Boston, MA USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Biomot Lab, RSH 010,40 Parkman St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG11255] NR 26 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 30 PY 2001 VL 106 IS 2 BP 171 EP 178 DI 10.1016/S0165-0270(01)00346-6 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 438FJ UT WOS:000169042700008 PM 11325437 ER PT J AU Macian, F Lopez-Rodriguez, C Rao, A AF Macian, F Lopez-Rodriguez, C Rao, A TI Partners in transcription: NFAT and AP-1 SO ONCOGENE LA English DT Review DE nuclear factor of activated T cells; Fos; Jun; transcriptional regulation ID ACTIVATED T-CELLS; FAS LIGAND EXPRESSION; ALPHA GENE PROMOTER; KINASE C-THETA; NUCLEAR FACTOR; CYCLOSPORINE-A; IN-VIVO; PHOSPHATASE CALCINEURIN; SIGNAL-TRANSDUCTION; PROTEIN-KINASES AB Combinatorial regulation is a powerful mechanism that enables tight control of gene expression, via integration of multiple signaling pathways that induce different transcription factors required for enhanceosome assembly. The four calcium-regulated transcription factors of the NFAT family act synergistically with AP-1 (Fos/Jun) proteins on composite DNA elements which contain adjacent NFAT and AP-1 binding sites, where they form highly stable ternary complexes to regulate the expression of diverse inducible genes. Concomitant induction of NFAT and AP-1 requires concerted activation of two different signaling pathways: calcium/calcineurin, which promotes NFAT dephosphorylation, nuclear translocation and activation; and protein kinase C (PKC)/Ras, which promotes the synthesis, phosphorylation and activation of members of the Fos and Jun families of transcription factors. A fifth member of the NFAT family, NFAT5, controls the cellular response to osmotic stress, by a mechanism that requires dimer formation and is independent of calcineurin or of interaction with AP-1. Pharmacological interference with the NFAT:AP-1 interaction may be useful in selective manipulation of the immune response. Balanced activation of NFAT and AP-1 is known to be required for productive immune responses, but the role of NFAT:AP-1 interactions in other cell types and biological processes remains to be understood. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Lopez-Rodriguez, C/G-4482-2014 OI Lopez-Rodriguez, C/0000-0002-2311-2406 FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI40127] NR 112 TC 444 Z9 460 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 30 PY 2001 VL 20 IS 19 BP 2476 EP 2489 DI 10.1038/sj.onc.1204386 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 430HP UT WOS:000168568700013 PM 11402342 ER PT J AU Ichinose, F Zapol, WM Sapirstein, A Ullrich, R Tager, AM Coggins, K Jones, R Bloch, KD AF Ichinose, F Zapol, WM Sapirstein, A Ullrich, R Tager, AM Coggins, K Jones, R Bloch, KD TI Attenuation of hypoxic pulmonary vasoconstriction by endotoxemia requires 5-lipoxygenase in mice SO CIRCULATION RESEARCH LA English DT Article DE cysteinyl leukotrienes; pulmonary injury; left mainstem bronchus occlusion ID ACUTE INFLAMMATORY RESPONSES; LEUKOTRIENE B-4 RECEPTOR; LUNG INJURY; TARGETED DISRUPTION; SHEEP; RATS; DYSFUNCTION; CHEMOTAXIS; PRODUCTS; PATHWAY AB Sepsis and endotoxemia impair hypoxic pulmonary vasoconstriction (HPV), thereby reducing systemic oxygenation. To assess the role of leukotrienes (LTs) in the attenuation of HPV during endotoxemia, the increase in left lung pulmonary vascular resistance (LPVR) before and during left mainstem bronchus occlusion (LMBO) was measured in mice with and without a deletion of the gene encoding 5-lipoxygenase (5-LO). LMBO increased the LPVR equally in saline-challenged wild-type and 5-LO-deficient mice (96 +/- 20% and 94 +/- 19%, respectively). Twenty-two hours after challenge with Escherichia coli endotoxin, the ability of LMBO to increase LPVR was markedly impaired in wild-type mice (27+/-7%; P<0.05) but not in 5-LO-deficient mice (72+/-9%) or in wild-type mice pretreated with MK886, an inhibitor of 5-LO activity (76+/-10%). Compared with wild-type mice, endotoxin-induced disruption of lung structures and inflammatory cell influx in the lung were markedly attenuated in 5-LO-deficient mice. Administration of MK571. a selective cysteinyl LT1 receptor antagonist, 1 hour before endotoxin challenge preserved HPV and attenuated pulmonary injury in wild-type mice but did not prevent the endotoxin-induced increase in pulmonary myeloperoxidase activity. Taken together, these findings demonstrate that a 5-LO product, most likely a cysteinyl LT, contributes to the attenuation of HPV and to pulmonary injury after challenge with endotoxin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. Univ N Carolina, Div Pulm & Crit Care Med, Chapel Hill, NC USA. RP Ichinose, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-42397, HL-55377]; NIDDK NIH HHS [P01-DK38108] NR 35 TC 24 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 27 PY 2001 VL 88 IS 8 BP 832 EP 838 DI 10.1161/hh0801.089177 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 428WW UT WOS:000168485500014 PM 11325876 ER PT J AU Manickan, E Satoi, JJ Wang, TC Liang, TJ AF Manickan, E Satoi, JJ Wang, TC Liang, TJ TI Conditional liver-specific expression of simian virus 40 T antigen leads to regulatable development of hepatic neoplasm in transgenic mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-EXPRESSION; MAMMALIAN-CELLS; HEPATOCELLULAR-CARCINOMA; IN-VIVO; SYSTEM; MOUSE; HEPATOCARCINOGENESIS; CARCINOGENESIS; DOXYCYCLINE; PROTEINS AB Adaptive epigenetic changes and toxicity often accompany constitutive expression of a transgene or knockout of an endogenous gene in mice. These considerations potentially limit the usefulness of transgenic technology in studying the in vivo functions of a gene. Using conditional gene expression technology, it is possible to override such restrictions to achieve temporal and tissue-specific manipulation of gene expression in vivo. Based on the tetracycline regulatory system, we established a binary transgenic model in which the conditional expression of two transgenes, SV40 T antigen (TAg) and lacZ, can be tightly regulated in the liver by administration of tetracycline. The mouse albumin or mouse major urinary protein promoter was used to achieve liver-specific expression of the tetracycline-responsive transcriptional activator (tTA) in one set of transgenic mice. These mice were crossed with transgenic mice carrying either TAg or lacZ under the control of the tTA-regulated promoter. Analyses of mice transgenic for both tTA and TAg (or lacZ) revealed that the liver-specific expression of the transgenes could be suppressed to undetectable levels and regulated in a reversible fashion by tetracycline administration and withdrawal. Mice with tTA and TAg transgenes developed hepatocellular adenomas and hyperplasia that could be prevented by continuous tetracycline administration. Our report demonstrates the value of this binary transgenic model in studying the physiological functions of any potential genes of interest in a liver-specific manner. C1 NIDDK, Liver Dis Sect, DDB, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, DDB, NIH, Bldg 10,Rm 9B16,10 Ctr Dr MSC 1800, Bethesda, MD 20892 USA. NR 33 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2001 VL 276 IS 17 BP 13989 EP 13994 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426PB UT WOS:000168356600067 PM 11278564 ER PT J AU Lo, KWH Naisbitt, S Fan, JS Sheng, M Zhang, MJ AF Lo, KWH Naisbitt, S Fan, JS Sheng, M Zhang, MJ TI The 8-kDa dynein light chain binds to its targets via a conserved (K/R)XTQT motif SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; INTERMEDIATE-CHAIN; HEAVY-CHAIN; PROTEIN INHIBITOR; MYOSIN-V; DIMERIZATION; PURIFICATION; INTERACTS; TRANSPORT; FLAGELLA AB Cytoplasmic dynein is a large, multisubunit molecular motor that translocates cargoes toward the minus ends of microtubules. Proper functioning of the dynein motor requires precise assembly of its various subunits. Using purified recombinant proteins, we show that the highly conserved 8-kDa light chain (DLC8) binds to the intermediate chain of the dynein complex. The DLC8-binding region was mapped to a highly conserved 10-residue fragment (amino acid sequence SYSKETQTPL) C-terminal to the second alternative splicing site of dynein intermediate chain. Yeast two-hybrid screening using DLC8 as bait identified numerous additional DLC8-binding proteins. Biochemical and mutational analysis of selected DLC8 binding proteins revealed that DLC8 binds to a consensus sequence containing a (K/R)XTQT motif. The (K/R)XTQT motif interacts with the common target-accepting grooves of DLC8 dimer. The role of each conserved amino acid residue in this pentapeptide motif in supporting complex formation with DLC8 was systematically studied using site-directed mutagenesis. C1 Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong, Peoples R China. 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 Zhang, MJ (reprint author), Hong Kong Univ Sci & Technol, Dept Biochem, Clear Water Bay, Kowloon, Hong Kong, Peoples R China. NR 28 TC 139 Z9 142 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2001 VL 276 IS 17 BP 14059 EP 14066 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426PB UT WOS:000168356600076 PM 11148209 ER PT J AU Wei, MC Zong, WX Cheng, EHY Lindsten, T Panoutsakopoulou, V Ross, AJ Roth, KA MacCregor, GR Thompson, CB Korsmeyer, SJ AF Wei, MC Zong, WX Cheng, EHY Lindsten, T Panoutsakopoulou, V Ross, AJ Roth, KA MacCregor, GR Thompson, CB Korsmeyer, SJ TI Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death SO SCIENCE LA English DT Article ID BCL-2 FAMILY MEMBERS; CYTOCHROME-C RELEASE; ENDOPLASMIC-RETICULUM; CELL-DEATH; APOPTOTIC PATHWAYS; PROTEIN; ACTIVATION; MEMBRANE; CASPASE-9; SURVIVAL AB Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a "BH3-domain-only" BCL-2 family member, triggers the homooligomerization of "multidomain" conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax and Bak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a "multidomain" proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli. C1 Univ Penn, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Dept Pathol,Howard Huges Med Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, Div Biol & Biomed Sci, St Louis, MO 63110 USA. Emory Univ, Sch Med, Ctr Mol Med, Atlanta, GA 30322 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. RP Thompson, CB (reprint author), Univ Penn, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA. OI Panoutsakopoulou, Vily/0000-0002-1569-1508; Roth, Kevin/0000-0002-0643-995X FU NCCIH NIH HHS [5T32AT09361]; NCI NIH HHS [R01CA50239, R37CA4802]; NICHD NIH HHS [R01 HD036437-02, R01 HD036437-03, R01 HD036437-04, R01 HD036437-05] NR 33 TC 2587 Z9 2658 U1 13 U2 131 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 27 PY 2001 VL 292 IS 5517 BP 727 EP 730 DI 10.1126/science.1059108 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 428TX UT WOS:000168478300051 PM 11326099 ER PT J AU Zorn, E Orsini, E Wu, CJ Stein, B Chillemi, A Canning, C Alyea, EP Soiffer, RJ Ritz, J AF Zorn, E Orsini, E Wu, CJ Stein, B Chillemi, A Canning, C Alyea, EP Soiffer, RJ Ritz, J TI A CD4+T cell clone selected from a CML patient after donor lymphocyte infusion recognizes BCR-ABL breakpoint peptides but not tumor cells SO TRANSPLANTATION LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; CYTOTOXIC T-LYMPHOCYTES; CLASS-I MOLECULES; DENDRITIC CELLS; JOINING REGION; CHRONIC PHASE; PROTEIN AB Background. In patients with chronic myelocytic leukemia (CML), the breakpoint cluster region and fusion between the BCR and the c-ABL genes (BCR-ABL) oncogen product is a potential tumor-specific antigen. Previous studies have shown that T cells specific for the junctional region peptides of the BCR-ABL oncoprotein can be detected in healthy individuals as well as in patients with CML in chronic phase. We assessed whether BCR-ABL- specific T cells could be found in a patient achieving a complete cytogenetic remission after CD4+ donor lymphocyte infusion. Methods. Using dendritic cells pulsed with BCR-ABL breakpoint peptides as antigen-presenting cells, we stimulated patient peripheral blood lymphocytes to isolate peptide-specific T cell clones present at the time of the cytogenetic response. T cell clones were isolated and the cellular specificity of these cells was examined. Results. A CD3+ CD4+ T cell clone (1F7) that recognizes overlapping p210 junctional peptides presented by HLA-DR molecules was identified and expanded in vitro. Clone 1F7 failed to recognize autologous tumor cells as well as dendritic cells derived from patient CML cells. Clone 1F7 did not inhibit the growth and differentiation of CML precursor cells in a standard colony formation assay. Finally, using a clone-specific probe, 1F7 cells could not be detected in patient peripheral blood at the time of the donor lymphocyte infusion response. Conclusions. These results suggest that clone 1F7 was selected in vitro using highly potent peptide pulsed dendritic cells but was not representative of the anti-leukemia immune response in vivo. Based on these findings, CD4+ T cells with BCR-ABL specificity do not appear to be mediators of the anti-leukemia response in vivo after donor lymphocyte infusion. C1 Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Ctr Hematol Oncol, Boston, MA 02115 USA. RP Ritz, J (reprint author), Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530] NR 32 TC 16 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2001 VL 71 IS 8 BP 1131 EP 1137 DI 10.1097/00007890-200104270-00021 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 436WA UT WOS:000168957800021 PM 11374415 ER PT J AU Lopez-Avalos, MD Tatarkiewicz, K Sharma, A Bonner-Weir, S Weir, GC AF Lopez-Avalos, MD Tatarkiewicz, K Sharma, A Bonner-Weir, S Weir, GC TI Enhanced maturation of porcine neonatal pancreatic cell clusters with growth factors fails to improve transplantation outcome SO TRANSPLANTATION LA English DT Article ID FETAL-RAT ISLETS; BETA-CELLS; NUDE-MICE; SODIUM-BUTYRATE; FACTOR-I; PLACENTAL-LACTOGEN; INSULIN-SECRETION; DIABETES-MELLITUS; FACTOR RECEPTORS; SCATTER FACTOR AB Background. Porcine neonatal pancreatic cell clusters (NPCC) are a potential source of islet tissue for clinical transplantation. They can normalize glycemia after transplantation, although after a relatively long (several weeks) period of time, possibly due to the immaturity of the tissue. Methods. One week after isolation NPCCs were immobilized in alginate hydrogel to be cultured for 2 more weeks in the presence of different growth factors, which were applied individually or in various combinations. Their effect was assessed by measuring DNA and insulin content, and expression of islet genes by reverse transcriptase-polymerase chain reaction. Enhanced maturation of NPCCs was also evaluated after transplantation in streptozotocin-diabetic mice. Results, A combination of fetal calf serum, insulin-like growth factor-I, nicotinamide and sodium butyrate in NPCCs media from day 7 to day 21 resulted in increased insulin/DNA content and higher expression of insulin, somatostatin, GLUT2 and Nkx6.1 genes. NPCCs cultured under the same conditions from day 3 to day 12 were transplanted into diabetic mice. Control mice were transplanted with NPCCs cultured in parallel in the presence of nicotinamide, but with no serum, insulin-like growth factor-I or butyrate. Normoglycemia was achieved at the same rate in both groups. Plasma porcine C-peptide (week 6) and graft insulin content (week 20) were also similar in both groups. Conclusions. Increased insulin content of NPCCs was achieved in vitro by addition of fetal calf serum, insulin-like growth factor-I, nicotinamide, and sodium butyrate, but this increase did not translate into a faster achievement of normoglycemia after transplantation, which suggests that there is a time frame required for complete maturation that is difficult to alter. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-53087, DK-36836] NR 55 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2001 VL 71 IS 8 BP 1154 EP 1162 DI 10.1097/00007890-200104270-00024 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 436WA UT WOS:000168957800024 PM 11374418 ER PT J AU Fishman, MC AF Fishman, MC TI The genomic cosmos SO NATURE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fishman, MC (reprint author), Harvard Univ, Sch Med, Fruit St, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 26 PY 2001 VL 410 IS 6832 BP 1033 EP 1033 DI 10.1038/35074219 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425HQ UT WOS:000168285500026 PM 11323648 ER PT J AU Johnson, L Mercer, K Greenbaum, D Bronson, RT Crowley, D Tuveson, DA Jacks, T AF Johnson, L Mercer, K Greenbaum, D Bronson, RT Crowley, D Tuveson, DA Jacks, T TI Somatic activation of the K-ras oncogene causes early onset lung cancer in mice SO NATURE LA English DT Article ID TUMOR-DEVELOPMENT; GENE-MUTATIONS; ADENOCARCINOMA; PROGRESSION; MOUSE; TRANSFORMATION; HYPERPLASIA; PREVALENCE; FREQUENT; FOCI AB About 30% of human tumours carry ras gene mutations(1,2). Of the three genes in this family (composed of K-ras, N-ras and H-ras), K-ras is the most frequently mutated member in human tumours, including adenocarcinomas of the pancreas (similar to 70-90% incidence), colon (similar to 50%) and lung (similar to 25-50%)(1-6). To constuct mouse tumour models involving K-ras, we used a new gene targeting procedure to create mouse strains carrying oncogenic alleles of K-ras that can be activated only on a spontaneous recombination event in the whole animal. Here we show that mice carrying these mutations were highly predisposed to a range of tumour types, predominantly early onset lung cancer. This model was further characterized by examining the effects of germline mutations in the tumour suppressor gene p53, which is known to be mutated along with K-ras in human tumours. This approach has several advantages over traditional transgenic strategies, including that it more closely recapitulates spontaneous oncogene activation as seen in human cancers. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. RP Jacks, T (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 31 TC 643 Z9 668 U1 0 U2 18 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 26 PY 2001 VL 410 IS 6832 BP 1111 EP 1116 DI 10.1038/35074129 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425HQ UT WOS:000168285500052 PM 11323676 ER PT J AU Kaushal, R Bates, DW Landrigan, C McKenna, DJ Clapp, MD Federico, F Goldmann, DA AF Kaushal, R Bates, DW Landrigan, C McKenna, DJ Clapp, MD Federico, F Goldmann, DA TI Medication errors and adverse drug events in pediatric inpatients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PHYSICIAN ORDER ENTRY; INTENSIVE-CARE UNIT; OF-MEDICINE REPORT; HOSPITALIZED-PATIENTS; PREVENTION; IMPROVEMENT; PHARMACISTS; MANAGEMENT AB Context latrogenic injuries, including medication errors, are an important problem in all hospitalized populations. However, few epidemiological data are available regarding medication errors in the pediatric inpatient setting. Objectives To assess the rates of medication errors, adverse drug events (ADEs), and potential ADEs; to compare pediatric rates with previously reported adult rates; to analyze the major types of errors; and to evaluate the potential impact of prevention strategies. Design, Setting, and Patients Prospective cohort study of 1120 patients admitted to 2 academic institutions during 6 weeks in April and May of 1999. Main Outcome Measures Medication errors, potential ADEs, and ADEs were identified by clinical staff reports and review of medication order sheets, medication administration records, and patient charts. Results We reviewed 10778 medication orders and found 616 medication errors (5.7%), 115 potential ADEs (1.1%), and 26 ADEs (0.24%). Of the 26 ADEs, 5 (19%) were preventable. While the preventable ADE rate was similar to that of a previous adult hospital study, the potential ADE rate was 3 times higher. The rate of potential ADEs was significantly higher in neonates in the neonatal intensive care unit. Most potential ADEs occurred at the stage of drug ordering (79%) and involved incorrect dosing (34%), anti-infective drugs (28%), and intravenous medications (54%), Physician reviewers judged that computerized physician order entry could potentially have prevented 93% and ward-based clinical pharmacists 94% of potential ADEs. Conclusions Medication errors are common in pediatric inpatient settings, and further efforts are needed to reduce them. C1 Childrens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Qual Improvement & Risk Management, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Risk Management Fdn, Cambridge, MA USA. RP Goldmann, DA (reprint author), Childrens Hosp, Dept Med, Enders 609,300 Longwood Ave, Boston, MA 02115 USA. FU AHRQ HHS [T32 HS00063] NR 31 TC 762 Z9 789 U1 5 U2 34 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 25 PY 2001 VL 285 IS 16 BP 2114 EP 2120 DI 10.1001/jama.285.16.2114 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 422QW UT WOS:000168131600032 PM 11311101 ER PT J AU Parker, RA Jenike, MA AF Parker, RA Jenike, MA TI A 45-year-old woman with obsessive-compulsive disorder SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SCHIZOTYPAL PERSONALITY-DISORDER; MAGNETIC-RESONANCE; SEROTONERGIC RESPONSIVITY; SYMPTOM PROVOCATION; DOUBLE-BLIND; ABNORMALITIES; CLOZAPINE; RISPERIDONE; MECHANISMS; TOMOGRAPHY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. McLean Hosp, OCD Inst, Belmont, MA 02178 USA. RP Parker, RA (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave,LY318, Boston, MA 02215 USA. NR 55 TC 6 Z9 6 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 25 PY 2001 VL 285 IS 16 BP 2121 EP 2128 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 422QW UT WOS:000168131600033 ER PT J AU Peskind, ER Wilkinson, CW Petrie, EC Schellenberg, GD Raskind, MA AF Peskind, ER Wilkinson, CW Petrie, EC Schellenberg, GD Raskind, MA TI Increased CSF cortisol in AD is a function of APOE genotype SO NEUROLOGY LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; HUMAN APOLIPOPROTEIN-E; Y1 ADRENAL-CELLS; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; COGNITIVE DECLINE; EPSILON-4 ALLELE; APOE(-/-) MICE; STRESS; BRAIN AB Background: Increased hypothalamic-pituitary-adrenal (HPA) axis activity manifested by elevated cortisol levels is observed in AD and may contribute to AD by lowering the threshold for neuronal degeneration. Presence of the APOE-epsilon4 allele increases risk for AD. Increased cortisol concentrations in apoE-deficient mice suggest that APOE genotype may influence cortisol concentrations in AD. Methods: The authors measured cortisol levels in CSF and determined APOE genotypes for 64 subjects with AD and 34 nondemented older control subjects, Results: CSF cortisol was significantly higher in AD than in control subjects. CSF cortisol concentrations differed with respect to APOE genotype in both subjects with,4D (epsilon/epsilon4 > epsilon3/4 epsilon > epsilon3/epsilon3) and normal older control subjects (epsilon3/epsilon4 > epsilon3/epsilon3 > epsilon3/epsilon3). Comparison of CSF cortisol concentrations within the epsilon3/epsilon4 and epsilon3/epsilon3 genotypes revealed no differences between AD and control subject groups. Conclusions: Higher CSF cortisol concentrations were associated with increased frequency of the APOE-epsilon4 allele and decreased frequency of the,APOE-epsilon2 allele in AD subjects relative to control subjects. This effect of APOE genotype on HPA axis activity may be related to the increased risk for 4D in persons carrying the APOE-epsilon4 allele and decreased risk for AD in persons carrying the APOE-epsilon2 allele. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr 116, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Peskind, ER (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr 116, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AGO8419, AGO5136] NR 48 TC 92 Z9 93 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 24 PY 2001 VL 56 IS 8 BP 1094 EP 1098 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 424ZN UT WOS:000168264000021 PM 11320185 ER PT J AU Kayo, T Allison, DB Weindruch, R Prolla, TA AF Kayo, T Allison, DB Weindruch, R Prolla, TA TI Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-EXPRESSION PROFILE; CYTOCHROME-C-OXIDASE; DIETARY RESTRICTION; ENERGY RESTRICTION; THYROID-HORMONE; COLLAGEN-III; CDNA; CHITOTRIOSIDASE; METABOLISM; CLONING AB In laboratory rodents, caloric restriction (CR) retards several age-dependent physiological and biochemical changes in skeletal muscle, including increased steady-state levels of oxidative damage to lipids, DNA, and proteins. We have previously used high-density oligonucleotide arrays to show that CR can prevent or delay most of the major age-related transcriptional alterations in the gastrocnemius muscle of C57BL/6 mice. Here we report the effects of aging and adult-onset CR on the gene expression profile of 7.070 genes in the vastus lateralis muscle from rhesus monkeys. Gene expression analysis of aged rhesus monkeys (mean age of 26 years) was compared with that of young animals (mean age of 8 years). Aging resulted in a selective up-regulation of transcripts involved in inflammation and oxidative stress, and a down-regulation of genes involved in mitochondrial electron transport and oxidative phosphorylation, Middle-aged monkeys (mean age of 20 years) subjected to CR since early adulthood (mean age of 11 years) were studied to determine the gene expression profile induced by CR, CR resulted in an up-regulation of cytoskeletal protein-encoding genes, and also a decrease in the expression of genes involved in mitochondrial bioenergetics, Surprisingly, we did not observe any evidence for an inhibitory effect of adult-onset CR on age-related changes in gene expression. These results indicate that the induction of an oxidative stress-induced transcriptional response may be a common feature of aging in skeletal muscle of rodents and primates, but the extent to which CR modifies these responses may be species-specific. C1 William S Middleton Mem Vet Hosp, Dept Med, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. Columbia Univ, St Lukes Roosevelt Hosp, Coll Phys & Surg, Dept Psychiat, New York, NY 10025 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Genet & Med Genet, Madison, WI 53706 USA. RP Weindruch, R (reprint author), William S Middleton Mem Vet Hosp, Dept Med, Geriatr Res Educ & Clin Ctr, GRECC 4D,2500 Overlook Terrace, Madison, WI 53705 USA. OI Allison, David/0000-0003-3566-9399 FU NCI NIH HHS [R01 CA 78732]; NIA NIH HHS [P01 AG011915, AG 11915] NR 26 TC 257 Z9 261 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5093 EP 5098 DI 10.1073/pnas.081061898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500054 PM 11309484 ER PT J AU Flores-Villanueva, PO Yunis, EJ Delgado, JC Vittinghoff, E Buchbinder, S Leung, JY Uglialoro, AM Clavijo, OP Rosenberg, ES Kalams, SA Braun, JD Boswell, SL Walker, BD Goldfeld, AE AF Flores-Villanueva, PO Yunis, EJ Delgado, JC Vittinghoff, E Buchbinder, S Leung, JY Uglialoro, AM Clavijo, OP Rosenberg, ES Kalams, SA Braun, JD Boswell, SL Walker, BD Goldfeld, AE TI Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; VIRUS TYPE-1 INFECTION; LONG-TERM NONPROGRESSORS; LOW VIRAL LOAD; CLASS-I; HLA-B; GENETIC RESTRICTION; HOMOSEXUAL-MEN; PROGRESSION; CELLS AB Certain HLA-B antigens have been associated with lack of progression to AIDS. HLA-B alleles can be divided into two mutually exclusive groups based on the expression of the molecular epitopes HLA-Bw4 and HLA-Bw6. Notably, in addition to its role in presenting viral peptides for immune recognition, the HLA-Bw4, but not HLA-Bw6, motif functions as a ligand for a natural killer cell inhibitory receptor (KIR). Here, we show that profound suppression of HIV-1 viremia is significantly associated with homozygosity for HLA-B alleles that share the HLA-Bw4 epitope. Furthermore, homozygosity for HLA-Bw4 alleles was also significantly associated with the ability to remain AIDS free and to maintain a normal CD4 T cell count in a second cohort of HIV-l-infected individuals with well defined dates of seroconversion. This association was independent of the presence of a mutation in CC chemokine receptor 5 (CCR5) associated with resistance to HIV-1 infection, and it was independent of the presence of HLA alleles that could potentially confound the results. We conclude that homozygosity for HLA-Bw4-bearing B alleles is associated with a significant advantage and that the HLA-Bw4 motif is important in AIDS pathogenesis. C1 Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94105 USA. San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. Liberty Med, New York, NY 10014 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Fenway Community Hlth Ctr, Boston, MA 02108 USA. RP Goldfeld, AE (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL059838, HL-59838, HL-29582, P01 HL029582]; NIAID NIH HHS [R01 AI028568, AI-28568, R37 AI028568] NR 40 TC 160 Z9 175 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5140 EP 5145 DI 10.1073/pnas.071548198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500062 PM 11309482 ER PT J AU Gonzalez, E Dhanda, R Bamshad, M Mummidi, S Geevarghese, R Catano, G Anderson, SA Walter, EA Stephan, KT Hammer, MF Mangano, A Sen, L Clark, RA Ahuja, SS Dolan, MJ Ahuja, SK AF Gonzalez, E Dhanda, R Bamshad, M Mummidi, S Geevarghese, R Catano, G Anderson, SA Walter, EA Stephan, KT Hammer, MF Mangano, A Sen, L Clark, RA Ahuja, SS Dolan, MJ Ahuja, SK TI Global survey of genetic variation in CCR5, RANTES, and MIP-1 alpha: Impact on the epidemiology of the HIV-1 pandemic SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR-5 GENE; DISEASE PROGRESSION; INFECTION; AIDS; POLYMORPHISM; TRANSMISSION; RESISTANCE; PATHOGENESIS; DETERMINANTS AB Expression of CC chemokine receptor 5 (CCR5), the major coreceptor for HIV-1 cell entry, and its ligands (e.g., RANTES and MIP-1 alpha) is widely regarded as central to the pathogenesis of HIV-1 infection. By surveying nearly 3,000 HIV+ and HIV- individuals from worldwide populations for polymorphisms in the genes encoding RANTES, MIP-1 alpha: and CCR5, we show that the evolutionary histories of human populations have had a significant impact on the distribution of variation in these genes, and that this may be responsible, in part, for the heterogeneous nature of the epidemiology of the HIV-1 pandemic, The varied distribution of RANTES haplotypes (AC, GC, and AC) associated with population-specific HIV-I transmission- and disease-modifying effects is a striking example. Homozygosity for the AC haplotype was associated with an increased risk of acquiring HIV-1 as well as accelerated disease progression in European Americans, but not in African Americans. Yet. the prevalence of the ancestral AC haplotype is high in individuals of African origin, but substantially lower in non-Africans. In a Japanese cohort, AG-containing RANTES haplotype pairs were associated with a delay in disease progression; however, we now show that their contribution to HIV-1 pathogenesis and epidemiology in other parts of the world is negligible because the AG haplotype is infrequent in non-far East Asians. Thus, the varied distribution of RANTES, MIP-1 alpha, and CCR5 haplotype pairs and their population-specific phenotypic effects on HIV-1 susceptibility and disease progression results in a complex pattern of biological determinants of HIV-1 epidemiology. These findings have important implications for the design, assessment, and implementation of effective HIV-I intervention and prevention strategies. C1 S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Purdue Pharmaceut, Norwalk, CT 06901 USA. Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, San Antonio, TX 78236 USA. Wilford Hall USAF Med Ctr, Infect Dis Serv, San Antonio, TX 78236 USA. Univ Arizona, Tucson, AZ 85721 USA. Hosp Pediat JP Garrahan, Buenos Aires, DF, Argentina. RP Dolan, MJ (reprint author), S Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 FU NIAID NIH HHS [AI43279, AI46326, R01 AI043279, R01 AI046326, R21 AI046326, R37 AI046326] NR 32 TC 185 Z9 192 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5199 EP 5204 DI 10.1073/pnas.091056898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500072 PM 11320252 ER PT J AU Carter, PH Gardella, TJ AF Carter, PH Gardella, TJ TI Zinc(II)-mediated enhancement of the agonist activity of histidine-substituted parathyroid hormone(1-14) analogues SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE parathyroid hormone; peptide hormone; G protein-coupled receptor; protein engineering; zinc-binding peptide; model alpha-helix ID EXTRACELLULAR LOOP; GLUCAGON RECEPTOR; SHORT PEPTIDES; ALPHA-HELICES; PROTEIN; LIGAND; BINDING; PTH; ACTIVATION; RESIDUES AB Previous studies on parathyroid hormone (PTH)(1-14) revealed that residues (1-9) played a dominant role in stimulating PTH-1 receptor-mediated increases in cAMP formation. In the present study, we examined the effects of installing a metal-binding motif in the (10-14) region of rat PTH(1-14) on the peptide's agonist activity. We found that substitution of histidine for the native asparagine at position 10 of PTH(1-14) provided a peptide that was approx. 8-fold more potent as all agonist in the presence of divalent zinc salts than it was in the absence of the metal. This enhancement in potency was dependent on the native histidine at position 14, the concentration of Zn(II) utilized, and did not occur with other divalent metal ions. The zinc-activated [His(10)]-PTH(1-14) peptide was blocked by a classical PTH-1 receptor antagonist. PTHrP(7-36), and did not activate the PTH-2 receptor. The zinc-mediated enhancing effect did not require the large N-terminal extracellular domain of the PTH-1 receptor. Although we were able to demonstrate that [His(10)]-PTH(1-14) binds Zn(II) using H-1-NMR, our spectroscopic studies (circular dichroism and nuclear magnetic resonance) were not consistent with the notion that zinc enhanced the activity of [His(10)]-PTH(1-14) simply by inducing a helical structure in the 10-14 region. Rather, the data suggest that the enhancement in cAMP potency arises from the formation of a ternary complex between [His(10)]-PTH(1-14), a zinc atom, and the extracellular loop/transmembrane domain region of the PTH-1 receptor. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 55 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK11794] NR 41 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 23 PY 2001 VL 1538 IS 2-3 BP 290 EP 304 DI 10.1016/S0167-4889(01)00080-5 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 429LT UT WOS:000168519100019 PM 11336800 ER PT J AU Kachnic, LA Shaw, JE Manning, MA Lauve, AD Neifeld, JP AF Kachnic, LA Shaw, JE Manning, MA Lauve, AD Neifeld, JP TI Gemcitabine following radiotherapy with concurrent 5-fluorouracil for nonmetastatic adenocarcinoma of the pancreas SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO 99) CY OCT 30-NOV 04, 1999 CL SAN ANTONIO, TEXAS SP Amer Soc Therapeut Radiol & Oncol DE pancreas cancer; adjuvant chemoradiotherapy; gemcitabine ID PHASE-II TRIAL; RADIATION-THERAPY; CURATIVE RESECTION; ADJUVANT THERAPY; CANCER; CARCINOMA; SURVIVAL; EXPERIENCE; FAILURE; FLUOROURACIL AB Gemcitabine has been shown to be an active agent in the treatment of pancreatic cancer. This study was conducted to prospectively examine the tolerance and early efficacy of adjuvant gemcitabine following radiotherapy with concurrent 5-fluorouracil (5-FU) for nonmetastatic pancreatic adenocarcinoma, Twenty-three patients, median age 64 years, were treated with combined modality therapy. Nine patients underwent tumor resection before chemoradiation; 14 patients with locally unresectable tumors received definitive chemoradiation. Radiotherapy utilized four fields to the tumor and lymphatics to 45 Gy, plus a lateral boost to 50.4 Gy, Concurrent 5-FU 500 mg/m(2)/day was administered on days 1-3 and 29-31, followed by 4 months of gemcitabine 1,000 mg/m(2)/week for 3 weeks (fourth week break). Adjuvant gemcitabine was well tolerated. Eighty-three percent of the patients completed three to four cycles, The primary dose-limiting toxicity was leukopenia, which was observed in 10 patients (43%), Nonhematologic toxicities were reported in five patients (22%), There were no cases of gemcitabine-induced radiation recall and there have been no deaths attributed to treatment toxicity, Median follow-up for the 23 patients was 12 months (range, 5-50); the actuarial median survival was 13 months. This report confirms that adjuvant gemcitabine following radiotherapy with concurrent 5-FU for nonmetastatic pancreatic adenocarcinoma can be safely administered. (C) 2001 Wiley-Liss, Inc. C1 Virginia Commonwealth Univ, Med Coll Virginia, Gastrointestinal Tumor Ctr, Richmond, VA 23298 USA. RP Kachnic, LA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 34 TC 34 Z9 35 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 20 PY 2001 VL 96 IS 2 BP 132 EP 139 DI 10.1002/ijc.1008 PG 8 WC Oncology SC Oncology GA 419DM UT WOS:000167934100010 PM 11291097 ER PT J AU Sazonova, IY Houng, AK Chowdhry, SA Robinson, BR Hedstrom, L Reed, GL AF Sazonova, IY Houng, AK Chowdhry, SA Robinson, BR Hedstrom, L Reed, GL TI The mechanism of a bacterial plasminogen activator intermediate between streptokinase and staphylokinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STREPTOCOCCUS-UBERIS; CRYSTAL-STRUCTURE; RECOMBINANT STAPHYLOKINASE; BINDING REGION; DOMAIN; COMPLEX; KINETICS; SITE; PURIFICATION; INHIBITOR AB The therapeutic properties of plasminogen activators are dictated by their mechanism of action. Unlike staphylokinase, a single domain protein, streptokinase, a 3-domain (alpha, beta, and gamma) molecule, nonproteolytically activates human (h)-plasminogen and protects plasmin from inactivation by alpha (2)-antiplasmin. Because a streptokinase-like mechanism was hypothesized to require the streptokinase gamma -domain, we examined the mechanism of action of a novel two-domain (alpha,beta) Streptococcus uberis plasminogen activator (SUPA), Under conditions that quench trace plasmin, SUPA nonproteolytically generated an active site in bovine (b)-plasminogen, SUPA also competitively inhibited the inactivation of plasmin by alpha (2)-antiplasmin, Still, the lag phase in active site generation and plasminogen activation by SUPA was at least 8-fold longer than that of streptokinase. Recombinant streptokinase gamma -domain bound to the b-plasminogen SUPA complex and significantly reduced these lag phases. The SUPA-b.plasmin complex activated b-plasminogen with kinetic parameters comparable to those of streptokinase for h-plasminogen. The SUPA-b.plasmin complex also activated h-plasminogen but with a lower k(cat) (25-fold) and k(cat)/K-m (7.9-fold) than SK. We conclude that a gamma -domain is not required for a streptokinase-like activation of b-plasminogen, However, the streptokinase gamma -domain enhances the rates of active site formation in b-plasminogen and this enhancing effect may be required for efficient activation of plasminogen from other species. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brandeis Univ, Grad Dept Biochem, Waltham, MA 02453 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, HSPH 2-127,677 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-57314] NR 34 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2001 VL 276 IS 16 BP 12609 EP 12613 DI 10.1074/jbc.M009265200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VN UT WOS:000168198600020 PM 11278483 ER PT J AU Daniel, PB Kieffer, TJ Leech, CA Habener, JF AF Daniel, PB Kieffer, TJ Leech, CA Habener, JF TI Novel alternatively spliced exon in the extracellular ligand-binding domain of the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1R) selectively increases ligand affinity and alters signal transduction coupling during spermatogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; PHOSPHOLIPASE-C ACTIVATION; MOLECULAR CHARACTERIZATION; FUNCTIONAL EXPRESSION; TISSUE DISTRIBUTION; CELL-MEMBRANES; MESSENGER-RNA; I RECEPTOR; G-PROTEINS; CLONING AB The expression of the paracrine signaling hormone pituitary adenylate cyclase-activating polypeptide (PACAP) is regulated in a cyclical fashion during the Ig-day spermatogenic cycle of the adult rat testis. The precise functions of PACAP in the development of germ cells are uncertain, but cycle- and stage-specific expression may augment cAMP-regulated gene expression in germ cells and associated Sertoli cells. Here we report the existence of a heretofore unrecognized exon in the extracellular domain of the PACAP type 1 receptor (PAC1R) that is alternatively spliced during the spermatogenic cycle in the rat testis, This splice variant encodes a full-length receptor with the insertion of an additional 72 base pairs encoding 24 amino acids (exon 3a) between coding exons 3 and 4. The PAC1R(3a) mRNA is preferentially detected in seminiferous tubules and is expressed at the highest levels in round spermatids and Sertoli cells. Analyses of ligand binding and signaling functions in stably transfected HEK293 cells expressing the two receptor isoforms reveals a 6-fold increase in the affinity of the PAC1R(3a) to bind PACAP-38, and alterations in its coupling to both cAMP and inositol phosphate signaling pathways relative to the wild type PAC1R. These findings suggest that the extracellular region between coding exons 3 and g of PAC1R may play an important role in the regulation of the relative ligand affinities and the relative coupling to G, (cAMP) and G, (inositol phosphates) signal transduction pathways during spermatogenesis. 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, Boston, MA 02114 USA. NR 39 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2001 VL 276 IS 16 BP 12938 EP 12944 DI 10.1074/jbc.M009941200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VN UT WOS:000168198600069 PM 11278585 ER PT J AU Cahill, CM Tzivion, G Nasrin, N Ogg, S Dore, J Ruvkun, G Alexander-Bridges, M AF Cahill, CM Tzivion, G Nasrin, N Ogg, S Dore, J Ruvkun, G Alexander-Bridges, M TI Phosphatidylinositol 3-kinase signaling inhibits DAF-16 DNA binding and function via 14-3-3-dependent and 14-3-3-independent pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; PROTEIN-KINASE-B; AGE-1 PI3 KINASE; CAENORHABDITIS-ELEGANS; FACTOR FKHR; GENE-EXPRESSION; FAMILY MEMBER; PHOSPHOENOLPYRUVATE CARBOXYKINASE; INSULIN; PHOSPHORYLATION AB In Caenorhabditis elegans, an insulin-like signaling pathway to phosphatidylinositol S-kinase (PI 3-kinase) and AKT negatively regulates the activity of DAF-16, a Forkhead transcription factor. We show that in mammalian cells, C, elegans DAF-16 is a direct target of AKT and that AKT phosphorylation generates 14-3-3 binding sites and regulates the nuclear/cytoplasmic distribution of DAF-16 as previously shown for its mammalian homologs FKHR and FKHRL1. In vitro, interaction of AKT-phosphorylated DAF-16 with 14-3-3 prevents DAF-16 binding to its target site in the insulin-like growth factor binding protein-1 gene, the insulin response element. In HepG2 cells, insulin signaling to PI 3-kinase/AKT inhibits the ability of a GAL4 DNA binding domain/DAF-16 fusion protein to activate transcription via the insulinlike growth factor binding protein-1-insulin response element, but not the GAL4 DNA binding site, which suggests that insulin inhibits the interaction of DAF-16 with its cognate DNA site. Elimination of the DAF-16/1433 association by mutation of the AKT/14-3-3 sites in DAF-16, prevents 14-3-3 inhibition of DAF-16 DNA binding and insulin inhibition of DAF-16 function. Similarly, inhibition of the DAF-16/14-3-3 association by exposure of cells to the PI 3-kinase inhibitor LY294002, enhances DAF-16 DNA binding and transcription activity. Surprisingly constitutively nuclear DAF-16 mutants that lack AKT/14-3-3 binding sites also show enhanced DNA binding and transcription activity in response to LY294002, pointing to a 14-3-3-independent mode of regulation. Thus, our results demonstrate at least two mechanisms, one 14-3-3-dependent and the other 14-3-3-independent, whereby PI S-kinase signaling regulates DAF-16 DNA binding and transcription function. C1 Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Alexander-Bridges, M (reprint author), Massachusetts Gen Hosp, Dept Med, Diabet Unit, 306 Wellman,50 Blossom St, Boston, MA 02114 USA. RI Tzivion, Guri/D-8954-2011 FU NCI NIH HHS [CA73818-1]; NIA NIH HHS [AG05790, AG14161]; NIDDK NIH HHS [DK57200A01, T32 DK07028-24]; NIGMS NIH HHS [GM58012] NR 38 TC 149 Z9 152 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2001 VL 276 IS 16 BP 13402 EP 13410 DI 10.1074/jbc.M010042200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VN UT WOS:000168198600128 PM 11124266 ER PT J AU Ivan, M Kondo, K Yang, HF Kim, W Valiando, J Ohh, M Salic, A Asara, JM Lane, WS Kaelin, WG AF Ivan, M Kondo, K Yang, HF Kim, W Valiando, J Ohh, M Salic, A Asara, JM Lane, WS Kaelin, WG TI HIF alpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O-2 sensing SO SCIENCE LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; PROLYL 4-HYDROXYLASE; HYPOXIA; COMPLEX; UBIQUITINATION; UBIQUITYLATION; ACCUMULATION; INHIBITION; ACTIVATION; SUBUNIT AB HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe2+, this protein modification may play a key role in mammalian oxygen sensing. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Microchem & Proteom Anal Facil, Cambridge, MA 02138 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu RI Ivan, Mircea/A-8109-2012 NR 26 TC 2722 Z9 2796 U1 7 U2 108 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 20 PY 2001 VL 292 IS 5516 BP 464 EP 468 DI 10.1126/science.1059817 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 423QB UT WOS:000168187300035 PM 11292862 ER PT J AU Watanabe, T Wu, T Catalano, PJ Ueki, T Satriano, R Benson, AB Hamilton, SR AF Watanabe, T Wu, T Catalano, PJ Ueki, T Satriano, R Benson, AB Hamilton, SR TI Molecular predictors of survival after adjuvant chemotherapy for colon cancer. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID II COLORECTAL-CANCER; 18Q ALLELIC LOSS; MICROSATELLITE INSTABILITY; MISMATCH REPAIR; CHROMOSOME 18Q; DCC PROTEIN; CELL-LINES; STAGE-II; CLINICOPATHOLOGICAL VARIABLES; ESOPHAGOGASTRIC JUNCTION AB Background: Adjuvant chemotherapy improves survival among patients with stage III colon cancer, but no reliable molecular predictors of outcome have been identified. Methods: We evaluated loss of chromosomal material (also called loss of heterozygosity or allelic loss) from chromosomes 18q, 17p, and 8p; cellular levels of p53 and p21(WAF1/CIP1) proteins; and microsatellite instability as molecular markers. We analyzed tumor tissue from 460 patients with stage III and high-risk stage II colon cancer who had been treated with various combinations of adjuvant fluorouracil, leucovorin, and levamisole to determine the ability of these markers to predict survival. Results: Loss of heterozygosity at 18q was present in 155 of 319 cancers (49 percent). High levels of microsatellite instability were found in 62 of 298 tumors (21 percent), and 38 of these 62 tumors (61 percent) had a mutation of the gene for the type II receptor for transforming growth factor beta1 (TGF-beta1). Among patients with microsatellite-stable stage III cancer, five-year overall survival after fluorouracil-based chemotherapy was 74 percent in those whose cancer retained 18q alleles and 50 percent in those with loss of 18q alleles (relative risk of death with loss at 18q, 2.75; 95 percent confidence interval, 1.34 to 5.65; P = 0.006). The five-year survival rate among patients whose cancer had high levels of microsatellite instability was 74 percent in the presence of a mutated gene for the type II receptor for TGF-beta1 and 46 percent if the tumor did not have this mutation (relative risk of death, 2.90; 95 percent confidence interval, 1.14 to 7.35; P = 0.03). Conclusions: Retention of 18q alleles in microsatellite-stable cancers and mutation of the gene for the type II receptor for TGF-beta1 in cancers with high levels of microsatellite instability point to a favorable outcome after adjuvant chemotherapy with fluorouracil-based regimens for stage III colon cancer. (N Engl J Med 2001;344:1196-206.) Copyright (C) 2001 Massachusetts Medical Society. C1 Univ Texas, MD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Div Gastrointestinal Liver Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Penn, Ctr Canc, Dept Hematol Oncol, Philadelphia, PA 19104 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. Eastern Cooperat Oncol Grp, Brookline, MA USA. RP Hamilton, SR (reprint author), Univ Texas, MD Anderson Canc Ctr, Div Pathol & Lab Med, 1515 Holcombe Blvd,Box 85,G1-3754, Houston, TX 77030 USA. FU NCI NIH HHS [CA21115, CA60100, CA62924, P50 CA062924, U10 CA021115, U10 CA023318] NR 78 TC 566 Z9 587 U1 0 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 19 PY 2001 VL 344 IS 16 BP 1196 EP 1206 DI 10.1056/NEJM200104193441603 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 422PM UT WOS:000168127600003 PM 11309634 ER PT J AU Perrin, JM AF Perrin, JM TI Should we operate on children with fluid in the middle ear? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 MassGen Hosp Children, Boston, MA 02114 USA. RP Perrin, JM (reprint author), MassGen Hosp Children, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 19 PY 2001 VL 344 IS 16 BP 1241 EP 1242 DI 10.1056/NEJM200104193441609 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 422PM UT WOS:000168127600009 PM 11309640 ER PT J AU Suliman, A Lam, A Datta, R Srivastava, RK AF Suliman, A Lam, A Datta, R Srivastava, RK TI Intracellular mechanisms of TRAIL: apoptosis through mitochondrial-dependent and -independent pathways SO ONCOGENE LA English DT Article DE TRAIL; death receptor; FADD; caspase; mitochondria; Bcl-2; Bcl-X-L ID CYTOCHROME-C RELEASE; CYTOTOXIC LIGAND TRAIL; PROGRAMMED CELL-DEATH; NF-KAPPA-B; MEDIATED APOPTOSIS; CANCER-CELLS; FAS LIGAND; IONIZING-RADIATION; BACULOVIRUS P35; CD95 APO-1/FAS AB Tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines that promotes apoptosis, TRAIL induces apoptosis via death receptors (DR4 and DR5) in a wide variety of tumor cells but not in normal cells. The objectives of this study are to investigate the intracellular mechanisms by which TRAIL induces apoptosis, The death receptor Fas, upon ligand binding, trimerizes and recruits the adaptor protein FADD through the cytoplasmic death domain of Fas, FADD then binds and activates procaspase-8. It is unclear whether FADD is required for TRAIL-induced apoptosis, Here we show that the signaling complex of DR4/DR5 is assembled in response to TRAIL binding. FADD and caspase-8, but not caspase-10, are recruited to the receptor, and cells deficient in either FADD or caspase-8 blocked TRAIL-induced apoptosis, In addition, TRAIL initiates the activation of caspases, the loss of mitochondrial transmembrane potential (Delta psi (m)), the cleavage of BID, and the redistribution of mitochondrial cytochrome c, Treatment of Jurkat cells with cyclosporin A delayed TRAIL-induced Delta psi (m), caspase-3 activation and apoptosis, Similarly, Overexpression of Bcl-2 or Bcl-X-L delayed, but did not inhibit, TRAIL-induced Delta psi (m) and apoptosis, In contrast, XIAP, cowpox virus CrmA and baculovirus p35 inhibited TRAIL-induced apoptosis, These data suggest that death receptors (DR4 and DR5) and Fas receptors induced apoptosis through identical signaling pathway, and TRAIL-induced apoptosis via both mitochondrial-dependent and -independent pathways. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Srivastava, RK (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 20 N Pine St, Baltimore, MD 21201 USA. NR 87 TC 239 Z9 249 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 19 PY 2001 VL 20 IS 17 BP 2122 EP 2133 DI 10.1038/sj.onc.1204282 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 422KH UT WOS:000168116700007 PM 11360196 ER PT J AU Mukamal, KJ Maclure, M Muller, JE Sherwood, JB Mittleman, MA AF Mukamal, KJ Maclure, M Muller, JE Sherwood, JB Mittleman, MA TI Prior alcohol consumption and mortality following acute myocardial infarction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-General-Internal Medicine CY MAY 05-06, 2000 CL BOSTON, MASSACHUSETTS SP Soc Gen Internal Med ID CORONARY HEART-DISEASE; MIDDLE-AGED MEN; CARDIOVASCULAR MORTALITY; HYPERTENSIVE PATIENTS; FIBRINOLYTIC FACTORS; PHYSICAL EXERTION; CONTROLLED TRIAL; BLOOD-PRESSURE; RISK; ETHANOL AB Context Studies have found that individuals who consume 1 alcoholic drink every 1 to 2 days have a lower risk of a first acute myocardial infarction (AMI) than abstainers or heavy drinkers, but the effect of prior drinking on mortality after AMI is uncertain. Objective To determine the effect of prior alcohol consumption on long-term mortality among early survivors of AMI. Design and Setting Prospective inception cohort study conducted at 45 US communi ly and tertiary care hospitals between August 1989 and September 1994, with a median follow-up of 3.8 years. Patients A total of 1913 adults hospitalized with AMI between 1989 and 1994. Main Outcome Measure All-cause mortality, compared by self-reported average weekly consumption of beer, wine, and liquor during the year prior to AMI. Results Of the 1913 patients, 896 (47%) abstained from alcohol, 696 (36%) consumed less than 7 alcoholic drinks/wk, and 321 (17%) consumed 7 or more alcoholic drinks/wk. Compared with abstainers, patients who consumed less than 7 drinks/wk had a lower all-cause mortality rate (3.4 vs 6.3 deaths per 100 person-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71) as did those who consumed 7 or more drinks/wk (2.4 vs 6.3 deaths per 100 person-years; HR, 0.38; 95% CI, 0.25-0.55; P<.001 for trend). After adjusting for propensity to drink and other potential confounders, increasing alcohol consumption remained predictive of lower mortality for less than 7 drinks/wk, with an adjusted HR of 0.79 (95% CI, 0.60-1.03), and for 7 or more drinks/wk, with an adjusted HR of 0.68 (95% CI, 0.45 1.05; P=.01 for trend). The association was similar for total and cardiovascular mortality, among both men and women, and among different types of alcoholic beverages. Conclusion Self-reported moderate alcohol consumption in the year prior to AMI is associated with reduced mortality following infarction. C1 Harvard Univ, Sch Publ Hlth, Beth Israel Deaconess Med Ctr, Dept Epidemiol,Div Gen Med & Primary Care, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Beth Israel Deaconess Med Ctr, Dept Epidemiol,Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Beth Israel Deaconess Med Ctr, Dept Hlth & Social Behav,Div Gen Med & Primary Ca, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Beth Israel Deaconess Med Ctr, Dept Hlth & Social Behav,Div Cardiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mukamal, KJ (reprint author), Harvard Univ, Sch Publ Hlth, Beth Israel Deaconess Med Ctr, Dept Epidemiol,Div Gen Med & Primary Care, Boston, MA 02215 USA. FU NHLBI NIH HHS [R01HL41016]; NIAAA NIH HHS [K23AA00299] NR 40 TC 104 Z9 104 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 18 PY 2001 VL 285 IS 15 BP 1965 EP 1970 DI 10.1001/jama.285.15.1965 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 420FY UT WOS:000167995900024 PM 11308432 ER PT J AU Herbert, V AF Herbert, V TI Summary for patients on genes for hemochromatosis (vol 133, 128, 2000) SO ANNALS OF INTERNAL MEDICINE LA English DT Correction C1 Mt Sinai New York Univ Hlth Syst, Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Herbert, V (reprint author), Mt Sinai New York Univ Hlth Syst, Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 17 PY 2001 VL 134 IS 8 BP 715 EP 715 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 423LJ UT WOS:000168177500014 PM 11304115 ER PT J AU Schwer, HD Lecine, P Tiwari, S Italiano, JE Hartwig, JH Shivdasani, RA AF Schwer, HD Lecine, P Tiwari, S Italiano, JE Hartwig, JH Shivdasani, RA TI A lineage-restricted and divergent beta-tubulin isoform is essential for the biogenesis, structure and function of blood platelets SO CURRENT BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR NF-E2; CHICKEN ERYTHROCYTES; HUMAN MEGAKARYOCYTES; MONOCLONAL-ANTIBODY; MESSENGER-RNA; MICROTUBULES; ISOTYPES; MICE; CYTOSKELETON; EXPRESSION AB Background: Mammalian megakaryocytes release blood platelets through a remarkable process of cytoplasmic fragmentation and de novo assembly of a marginal microtubule band. Cell-specific components of this process include the divergent beta -tubulin isoform beta1 that is expressed exclusively, and is the predominant isoform, in platelets and megakaryocytes. The functional significance of this restricted expression, and indeed of the surprisingly large repertoire of metazoan tubulin genes, is unclear. Fungal tubulin isoforms appear to be functionally redundant, and all mammalian beta -tubulins can assemble in a variety of microtubules, whereas selected fly and worm beta -tubulins are essential in spermatogenesis and neurogenesis, To address the essential role of beta1-tubulin in its natural context, we generated mice with targeted gene disruption. Results: beta1-tubulin(-/-) mice have thrombocytopenia resulting from a defect in generating proplatelets, the immediate precursors of blood platelets. Circulating platelets lack the characteristic discoid shape and have defective marginal bands with reduced microtubule ceilings. beta1-tubulin(-/-) mice also have a prolonged bleeding time, and their platelets show an attenuated response to thrombin. Two alternative tubulin isoforms, beta2 and beta5, are overexpressed, and the total beta -tubulin content of beta1-tubulin(-/-) megakaryocytes is normal. However, these isoforms assemble much less efficiently into platelet microtubules and are thus unable to compensate completely for the absence of beta1-tubulin, Conclusions: This is the first genetic study to address the essential functions of a mammalian tubulin isoform in vivo. The results establish a specialized role for beta1-tubulin in platelet synthesis, structure, and function. C1 Dana Farber Canc Inst, Dept Adult Oncol & Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol & Canc Biol, Boston, MA 02115 USA. RI Tiwari, Sanjay/Q-1853-2016; Lecine, Patrick/H-9338-2016 OI Tiwari, Sanjay/0000-0002-3804-3300; FU NHLBI NIH HHS [R01-HL56252, R01-HL63143] NR 36 TC 133 Z9 135 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 17 PY 2001 VL 11 IS 8 BP 579 EP 586 DI 10.1016/S0960-9822(01)00153-1 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 433ET UT WOS:000168746800021 PM 11369202 ER PT J AU Lechner, O Lauber, J Franzke, A Sarukhan, A von Boehmer, H Buer, J AF Lechner, O Lauber, J Franzke, A Sarukhan, A von Boehmer, H Buer, J TI Fingerprints of anergic T cells SO CURRENT BIOLOGY LA English DT Article ID NEGATIVE REGULATION; EFFECTOR FUNCTION; RECEPTOR; PROLIFERATION; INHIBITION; CYCLE; TRANSCRIPTION; INTERLEUKIN-2; LYMPHOCYTES; EXPRESSION AB Peripheral T cell tolerance may result from activation-induced cell death [1], anergy [1], and/or immune response modulation by regulatory T cells [2], In mice that express a transgenic receptor specific for peptide 111-119 of influenza hemagglutinin presented by Ed class II MHC molecules as well as hemagglutinin under central of the immunoglobulin-le promoter, we have found that anergic T cells [3] can also have immunoregulatory function and secrete IL-10 [4], In order to obtain information on molecular mechanisms involved in anergy and immunoregulation, we have compared expression levels of 1176 genes in anergic, naive, and recently activated CD4(+) T cells of the same specificity by gene array analysis. The results provide a plausible explanation for the anergic phenotype in terms of proliferation, provide new information on the surface phenotype of in vivo-generated anergic CD4(+) T cells, and yield clues with regard to new candidate genes that may be responsible for the restricted cytokine production of in vivo-anergized CD4+ T cells. The molecular fingerprints of such T cells should enable the tracking of this small population in the normal organism and the study of their role in immunoregulation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Necker, INSERM, U373, F-75730 Paris, France. German Res Ctr Biotechnol, Mucosal Immun Grp, D-38124 Braunschweig, Germany. Hannover Med Sch, Dept Hematol & Oncol, D-3000 Hannover, Germany. Hannover Med Sch, Inst Med Microbiol, D-3000 Hannover, Germany. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 76 Z9 79 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 17 PY 2001 VL 11 IS 8 BP 587 EP 595 DI 10.1016/S0960-9822(01)00160-9 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 433ET UT WOS:000168746800022 PM 11369203 ER PT J AU Ellisen, LW Carlesso, N Cheng, T Scadden, DT Haber, DA AF Ellisen, LW Carlesso, N Cheng, T Scadden, DT Haber, DA TI The Wilms tumor suppressor WT1 directs stage-specific quiescence and differentiation of human hematopoietic progenitor cells SO EMBO JOURNAL LA English DT Article DE hematopoiesis; leukemia; tumor suppressor; WT1 ID NO PROGNOSTIC RELEVANCE; GENE WT1; STEM-CELLS; TRANSCRIPTIONAL ACTIVATION; SUBNUCLEAR LOCALIZATION; MYELOID DIFFERENTIATION; LIMITING-DILUTION; SCID/SCID MICE; HL-60 CELLS; IN-VITRO AB WT1, a transcription factor implicated in both normal kidney differentiation and tumorigenesis, is also expressed in differentiating hematopoietic progenitors. Most human acute leukemias contain high levels of the wild-type transcript, while a minority have point mutations, raising the possibility that this tumor suppressor might have a paradoxical oncogenic effect in some hematopoietic cells. Using high titer retroviral infection, we demonstrate that I WT1 triggers rapid growth arrest and lineage-specific differentiation in primary hematopoietic progenitors and differentiation-competent leukemia cell lines, while it induces cellular quiescence in a primitive subset of primary precursors. Growth arrest by WT1 is associated with induction of p21(CIP1), but expression of this cyclin-dependent kinase inhibitor alone is insufficient for either cellular differentiation or primitive cell preservation. The effects of WT1 are enhanced by coexpression of its naturally occurring isoforms, and are correlated with the physiological expression pattern of WT1 in vivo. Our observations suggest a role for WT1 in the differentiation of human hematopoietic cells, and provide a functional model that supports its capacity as a tumor suppressor in human acute leukemia. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [R37 CA058596, CA58596, R01 CA058596, CA82831]; NHLBI NIH HHS [R01 HL044851, HL44851]; NIDDK NIH HHS [K08 DK002761, R01 DK050234, DK02761, DK50234] NR 63 TC 109 Z9 114 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 17 PY 2001 VL 20 IS 8 BP 1897 EP 1909 DI 10.1093/emboj/20.8.1897 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 425WC UT WOS:000168313800008 PM 11296223 ER PT J AU Friedman, JS Rebel, VI Derby, R Bell, K Huang, TT Kuypers, FA Epstein, CJ Burakoff, SJ AF Friedman, JS Rebel, VI Derby, R Bell, K Huang, TT Kuypers, FA Epstein, CJ Burakoff, SJ TI Absence of mitochondrial superoxide dismutase results in a murine hemolytic anemia responsive to therapy with a catalytic antioxidant SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE transplantation (fetal liver); oxidative stress; antioxidant; stem cells; SOD2 ID IDIOPATHIC SIDEROBLASTIC ANEMIA; OXIDATIVE STRESS; LIFE-SPAN; MUTANT MICE; INDUCED DAMAGE; INJURY; EUK-8; DNA; RESISTANCE; ANTIBODIES AB Manganese superoxide dismutase 2 (SOD2) is a critical component of the mitochondrial pathway for detoxification of O-2(-), and targeted disruption of this locus leads to embryonic or neonatal lethality in mice. To follow the effects of SOD2 deficiency in cells over a longer time course, we created hematopoietic chimeras in which all blood cells are derived from fetal liver stem cells of Sod2 knockout, heterozygous, or wild-type littermates. Stem cells of each genotype efficiently rescued hematopoiesis and allowed long-term survival of lethally irradiated host animals. Peripheral blood analysis of leukocyte populations revealed no differences in reconstitution kinetics of T cells, B cells, or myeloid cells when comparing Sod2(+/+), Sod2(-/-), and Sod2(+/-) fetal liver recipients. However, animals receiving Sod2(-/-) cells were persistently anemic, with findings suggestive of a hemolytic process. Loss of SOD2 in erythroid progenitor cells results in enhanced protein oxidative damage, altered membrane deformation, and reduced survival of red cells. Treatment of anemic animals with Euk-8, a catalytic antioxidant with both SOD and catalase activities, significantly corrected this oxidative stress-induced condition. Such therapy may prove useful in treatment of human disorders such as sideroblastic anemia, which SOD2 deficiency most closely resembles. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. RP Friedman, JS (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Rm M654, Boston, MA 02115 USA. FU NCI NIH HHS [P01CA39542, P01 CA039542]; NHLBI NIH HHS [HL03748]; NIA NIH HHS [AG14694, AG16998]; NIDDK NIH HHS [P01 DK032094, DK32094] NR 38 TC 51 Z9 51 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 16 PY 2001 VL 193 IS 8 BP 925 EP 934 DI 10.1084/jem.193.8.925 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 423WC UT WOS:000168199900005 PM 11304553 ER PT J AU Hancock, WW Gao, W Csizmadia, V Faia, KL Shemmeri, N Luster, AD AF Hancock, WW Gao, W Csizmadia, V Faia, KL Shemmeri, N Luster, AD TI Donor-derived IP-10 initiates development of acute allograft rejection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE chemokine; transplantation; rejection; IP-10; endothelium ID CHEMOKINE RECEPTORS; T-CELLS; INDUCIBLE PROTEIN-10; CARDIAC ALLOGRAFTS; IFN-GAMMA; EXPRESSION; CXCR3; RAT AB An allograft is often considered an immunologically inert playing field on which host leukocytes assemble and wreak havoc. However, we demonstrate that graft-specific physiologic responses to early injury initiate and promulgate destruction of vascularized grafts. Serial analysis of allografts showed that intragraft expression of the three chemokine ligands for the CXC chemokine receptor CXCR3 was induced in the order of interferon (IFN)-gamma -inducible protein of 10 kD (IP-10, or CXCL10), IFN-inducible T cell alpha -chemoattractant (I-TAC; CXCL11). and then monokine induced by IFN-gamma (Mig, CXCL9). Initial IP-10 production was localized to endothelial cells, and only IP-10 was induced by isografting. Anti-IP-10 monoclonal antibodies prolonged allograft survival, but surprisingly, IP-10-deficient (IP-10(-/-)) mice acutely rejected allografts. However, though allografts from IP-10(+/+) mice were rejected by day 7, hearts from IP-10(-/-) mice survived long term. Compared with IP-10(+/+) donors, use of IP-10(-/-) donors reduced intragraft expression of cytokines, chemokines and their receptors, and associated leukocyte infiltration and graft injury. Hence, tissue-specific generation of a single chemokine in response to initial ischemia/reperfusion can initiate progressive graft infiltration and amplification of multiple effector pathways, and targeting of this proximal chemokine can prevent acute rejection. These data emphasize the pivotal role of donor-derived IP-10 in initiating alloresponses, with implications for tissue engineering to decrease immunogenicity, and demonstrate that chemokine redundancy may not be operative in vivo. C1 Millennium Pharmaceut Inc, Transplantat Unit, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hancock, WW (reprint author), Millennium Pharmaceut Inc, Transplantat Unit, 75 Sidney St, Cambridge, MA 02139 USA. NR 25 TC 295 Z9 305 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 16 PY 2001 VL 193 IS 8 BP 975 EP 980 DI 10.1084/jem.193.8.975 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 423WC UT WOS:000168199900010 PM 11304558 ER PT J AU O'Callaghan, PA Poloniecki, J Sosa-Suarez, G Ruskin, JN McGovern, BA Garan, H AF O'Callaghan, PA Poloniecki, J Sosa-Suarez, G Ruskin, JN McGovern, BA Garan, H TI Long-term clinical outcome of patients with prior myocardial infarction after palliative radiofrequency catheter ablation for frequent ventricular tachycardia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; ENTRAINMENT; SITES AB Patients with coronary artery disease and hemodynamically tolerated, highly frequent, sustained monomorphic ventricular tachycardia (VT) may undergo radiofrequency catheter ablation (RFCA) for elimination of greater than or equal to1 morphologically distinct Vis. The purpose of this study was to evaluate the lone-term clinical benefit following RFCA as a palliative treatment of highly frequent or incessant ischemic VT. Fifty-five patients underwent RFCA of 62 VTs. The target VT was successfully ablated in 82% of patients. Complication and perioperative mortality rates were 7.2% and 1.8%, respectively. At 5 years, total mortality was 51% and probability of freedom from all ventricular tachyarrhythmias was 28%. All patients had highly frequent or incessant drug-refractory VT before RFCA. Clinical benefit was defined as either freedom from all ventricular tachyarrhythmias, or a reduction in frequency of recurrence from >1 episode per month before RFCA to greater than or equal to1 episode per year of any ventricular tachyarrhythmia, including all appropriate implantable cardioverter defibrillator (ICD) therapies. By this definition, 54% of the patients continued to benefit from RFCA at 5 years. Of 19 variables analyzed with a Cox univariate model, only the presence of a left ventricular aneurysm and a previously implanted ICD were predictive of any ventricular arrhythmia recurrence. However, at 5 years over half of the surviving patients still continued to benefit from RFCA of their clinical VT. Because the overall rate of any ventricular tachyarrhythmia occurrence during follow-up is high, additional protection, such as an ICD, is required. (C) 2001 by Excerpta Medico, Inc. C1 Univ Texas, Sch Med, Div Cardiol, Houston, TX 77030 USA. St George Hosp, Sch Med, Dept Cardiol Sci, London SW17 0RE, England. St Peters Hosp, Albany, NY USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Univ Texas, Sch Med, Houston, TX USA. RP Garan, H (reprint author), Univ Texas, Sch Med, Div Cardiol, 6431 Fannin,MSB 1-246, Houston, TX 77030 USA. NR 12 TC 27 Z9 27 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2001 VL 87 IS 8 BP 975 EP 979 DI 10.1016/S0002-9149(01)01432-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 421AJ UT WOS:000168039700009 PM 11305989 ER PT J AU Hooper, BA Domankevitz, Y Anderson, RR Lin, C AF Hooper, BA Domankevitz, Y Anderson, RR Lin, C TI Optical temperature probe SO APPLIED PHYSICS LETTERS LA English DT Article ID TISSUE ABLATION; LASER ABLATION; WAVES; PULSES; WATER AB In order to quantify the energy deposition at a dielectric-tissue interface, a simple optical Temperature probe to measure the transient temperature rise of the laser-heated layer at this interface is presented. The optical temperature probe (1) is noninvasive, so as not to alter the optical, thermal. and mechanical properties of the sample, (2) has a fast time response (nanoseconds), in order to measure the temperature increase during a short laser pulse, and (3) has high spatial resolution (micrometers), in order to probe only the heated layer. The probe is also capable of detecting ablation at the optic-tissue interface. (C) 2001 American Institute of Physics. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Hooper, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. NR 18 TC 4 Z9 4 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD APR 15 PY 2001 VL 78 IS 16 BP 2381 EP 2383 DI 10.1063/1.1364509 PG 3 WC Physics, Applied SC Physics GA 425EK UT WOS:000168275200039 ER PT J AU Heckers, S AF Heckers, S TI Neuroimaging and postmortem studies of the hippocampus in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. McLean Hosp, Belmont, MA 02178 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 12 BP 4S EP 4S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000012 ER PT J AU Michelson, D Wernicke, J Heiligenstein, J Allen, AJ Faries, D Spencer, T Kratochvil, C AF Michelson, D Wernicke, J Heiligenstein, J Allen, AJ Faries, D Spencer, T Kratochvil, C TI Efficacy of LY139603 (tomoxetine), a non-dopaminergic intervention for ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Lilly Res Labs, Indianapolis, IN USA. Indiana Univ, Sch Med, Bloomington, IN 47405 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Nebraska, Sch Med, Lincoln, NE 68583 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 55 BP 15S EP 16S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000055 ER PT J AU Spencer, TJ Biederman, J AF Spencer, TJ Biederman, J TI Pharmacologic evidence for non-dopaminergic mechanisms in ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 52 BP 15S EP 15S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000052 ER PT J AU Deicken, RF Eliaz, Y Chosiad, L Feiwell, RJ Schuff, N AF Deicken, RF Eliaz, Y Chosiad, L Feiwell, RJ Schuff, N TI Proton MRSI of prefrontal-thalamic-cerebellar circuits in bipolar I disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 San Francisco Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, Magnet Resonance Unit, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 94 BP 27S EP 27S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000094 ER PT J AU Allen, AJ Spencer, TJ Heiligenstein, JH Faries, DE Kelsey, DK Laws, HF Wernicke, J Kendrick, KL Michelson, D AF Allen, AJ Spencer, TJ Heiligenstein, JH Faries, DE Kelsey, DK Laws, HF Wernicke, J Kendrick, KL Michelson, D TI Safety and efficacy of tomoxetine for ADHD in two double-blind, placebo-controlled trials SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 114 BP 32S EP 33S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000112 ER PT J AU Li, X Nahas, Z Oliver, NC Anderson, B Chae, JH Molloy, M George, MS AF Li, X Nahas, Z Oliver, NC Anderson, B Chae, JH Molloy, M George, MS TI Initial results using left prefrontal rTMS as a maintenance treatment for bipolar depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Funct Neuroimaging Div, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Brain Stimulat Lab, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 127 BP 36S EP 36S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000125 ER PT J AU Pincus, SH Cawthra, EM McRae, KA Braff, DL Adler, LE AF Pincus, SH Cawthra, EM McRae, KA Braff, DL Adler, LE TI Impaired auditory sensory gating in soldiers preparing for extended deployment to Bosnia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver VAMC, Denver, CO USA. USA, Med Corps, Washington, DC USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. USN Reserve, Washington, DC USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 138 BP 39S EP 39S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000136 ER PT J AU Erhart, SM Wirshing, DA Rossotto, E Pien, J Champion, KM Marder, SR Wirshing, WC AF Erhart, SM Wirshing, DA Rossotto, E Pien, J Champion, KM Marder, SR Wirshing, WC TI The emergence of EEG abnormalities for clozapine and haloperidol: Lack of association with treatment response and plasma levels (Results of a prospective double blind study) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 186 BP 53S EP 53S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000183 ER PT J AU Messamore, E Hoffmann, WF Janowsky, A AF Messamore, E Hoffmann, WF Janowsky, A TI Diminished skin flush response to niacin in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 192 BP 54S EP 54S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000189 ER PT J AU Yao, JK Sistilli, CG vanKammen, DP AF Yao, JK Sistilli, CG vanKammen, DP TI Membrane polyunsaturated fatty acids and cytokines in schizophrenic patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 193 BP 54S EP 55S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000190 ER PT J AU Goodman, M Mitropoulou, V New, A Koenigsberg, H Reynolds, D Breier, A Elman, I Siever, L AF Goodman, M Mitropoulou, V New, A Koenigsberg, H Reynolds, D Breier, A Elman, I Siever, L TI Frontal cortex dysfunction and subcortical dopaminergic activity in schizophrenia spectrum SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Bronx VA Med Ctr, Bronx, NY USA. Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 195 BP 55S EP 55S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000192 ER PT J AU Levitt, JJ McCarley, RW Ciszewski, A Salisbury, DF Kikinis, R Jolesz, FA Shenton, ME AF Levitt, JJ McCarley, RW Ciszewski, A Salisbury, DF Kikinis, R Jolesz, FA Shenton, ME TI An MRI study of caudate nucleus and lateral ventricle volume in first episode schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VA Boston Healthcare, Brockton Div, Dept Psychiat, Clin Neurosci Div,Lab Neurosci, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Radiol, MRI Div,Surg Planning Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 203 BP 57S EP 57S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000200 ER PT J AU Dickey, C McCarley, RW Volgmaier, M Niznikiewicz, M Frumin, M Seidman, L Shenton, ME AF Dickey, C McCarley, RW Volgmaier, M Niznikiewicz, M Frumin, M Seidman, L Shenton, ME TI Neurobiology of schizotypal personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 244 BP 69S EP 69S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000239 ER PT J AU Goodman, M New, A Mitropoulou, V Koenigsberg, H Weiss, D Siever, L AF Goodman, M New, A Mitropoulou, V Koenigsberg, H Weiss, D Siever, L TI Pathological dissociation in borderline personality disorder: The role of childhood trauma and serotonergic genes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Bronx VA Med Ctr, Bronx, NY USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 248 BP 70S EP 70S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000243 ER PT J AU Dougherty, DD Baer, L Cosgrove, GR Cassem, EH Price, BH Nierenberg, AA Jenike, MA Rauch, SL AF Dougherty, DD Baer, L Cosgrove, GR Cassem, EH Price, BH Nierenberg, AA Jenike, MA Rauch, SL TI Update on cingulotomy for intractable obsessive-compulsive disorder: Prospective follow-up of 44 patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 287 BP 82S EP 82S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000282 ER PT J AU Rauch, SL Dougherty, DD Cosgrove, GR Cassem, EH Alpert, NM Price, BH Nierenberg, AA Mayberg, HS Baer, L Jenike, MA Fischman, AJ AF Rauch, SL Dougherty, DD Cosgrove, GR Cassem, EH Alpert, NM Price, BH Nierenberg, AA Mayberg, HS Baer, L Jenike, MA Fischman, AJ TI Cerebral metabolic predictors of response to anterior cingulotomy for obsessive-compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. McLean Hosp, Dept Neurol, Belmont, MA 02178 USA. Univ Toronto, Rotman Res Inst, Dept Psychiat, Toronto, ON, Canada. Univ Toronto, Rotman Res Inst, Dept Neurol, Toronto, ON, Canada. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 288 BP 83S EP 83S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000283 ER PT J AU Koenigsberg, HW Buchsbaum, MS Harvey, P Cheung, A Tang, C New, AS Goodman, M Siever, LJ AF Koenigsberg, HW Buchsbaum, MS Harvey, P Cheung, A Tang, C New, AS Goodman, M Siever, LJ TI Regional brain activation in schizotypal personality disorder patients during a visuospatial working memory task as measured by fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 327 BP 94S EP 95S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000322 ER PT J AU Rogers, LJ Gordon, KA Eliaz, Y Cardenas-Nicholson, V Decken, RF AF Rogers, LJ Gordon, KA Eliaz, Y Cardenas-Nicholson, V Decken, RF TI Cortical grey matter abnormalities in bipolar I disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 San Francisco Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 335 BP 96S EP 97S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000330 ER PT J AU Dickey, CC Shenton, ME Voglmaier, MM Niznikiewicz, MA Seidman, LJ Frumin, M Fraone, S Ahn, S Madan, A McCarley, RW AF Dickey, CC Shenton, ME Voglmaier, MM Niznikiewicz, MA Seidman, LJ Frumin, M Fraone, S Ahn, S Madan, A McCarley, RW TI Prefrontal cortex in schizotypal personality disorder males and females SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Med Sch, Boston VA Healthcare Syst, Neuroimaging Lab, Boston, MA USA. Harvard Med Sch, Massachusetts Mental Hlth Ctr, Boston, MA USA. Boston Coll, Chestnut Hill, MA 02167 USA. Wellesley Coll, Wellesley, MA 02181 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 336 BP 97S EP 97S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000331 ER PT J AU Fava, M McGrath, PJ Sheu, WP Froeschke, M AF Fava, M McGrath, PJ Sheu, WP Froeschke, M TI Switching to reboxetine in fluoxetine-resistant patients: Efficacy and safety SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. New York State Psychiat Inst, New York, NY 10032 USA. Pharmacia Corp, Toronto, ON, Canada. Pharmacia Corp, Kalamazoo, MI USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 363 BP 104S EP 104S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000357 ER PT J AU Arciniegas, DB Topkoff, JL Filley, CM Adler, LE AF Arciniegas, DB Topkoff, JL Filley, CM Adler, LE TI Normalization of P50 physiology by donepezil hydrochloride in traumatic brain injury patient SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Denver Vet Affairs Med Ctr, Res Serv, Denver, CO USA. Denver Res Inst, Denver, CO USA. Denver Vet Affairs Med Ctr, Psychiat Serv, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Neuropsychiat Serv, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Behav Neurol Sect, Denver, CO 80262 USA. RI Arciniegas, David/A-3792-2009 NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 368 BP 106S EP 106S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000362 ER PT J AU Chae, JH Oliver, NC Nahas, Z Li, X Benjamin, B Sallee, FR George, MS AF Chae, JH Oliver, NC Nahas, Z Li, X Benjamin, B Sallee, FR George, MS TI Does transcranial magnetic stimulation (TMS) over motor or prefrontal cortex modify TICS in patients with Tourette's syndrome? A pilot study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Funct Neuroimaging Div, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 394 BP 113S EP 113S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000387 ER PT J AU DeVeaugh-Geiss, J Biederman, J Conners, CK Dietrich, A Laurenza, A Webster, C Barrows, C Asgharnejad, M AF DeVeaugh-Geiss, J Biederman, J Conners, CK Dietrich, A Laurenza, A Webster, C Barrows, C Asgharnejad, M TI GW320659 in the treatment of adult attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Glaxo Wellcome Inc, Res & Dev, Res Triangle Pk, NC 27709 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC USA. Neuropsychiat Associates, Woodstock, VT USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 408 BP 117S EP 117S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000401 ER PT J AU Henry, ME Moore, CM Demopolas, C Cote, J Renshaw, PF AF Henry, ME Moore, CM Demopolas, C Cote, J Renshaw, PF TI A comparison of brain lithium levels attained with immediate and sustained release lithium SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Combined Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 413 BP 119S EP 119S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000406 ER PT J AU Koenigsberg, HW Goodman, M Reynolds, D Mitropoulou, V Trestman, R Kirrane, R New, AS Anwunah, I Siever, LJ AF Koenigsberg, HW Goodman, M Reynolds, D Mitropoulou, V Trestman, R Kirrane, R New, AS Anwunah, I Siever, LJ TI Risperidone in the treatment of schizotypal personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 415 BP 119S EP 120S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000408 ER PT J AU Reddy, RD Keshavan, MS Yao, JK AF Reddy, RD Keshavan, MS Yao, JK TI Reduced plasma antioxidants in first-episode schizophrenic patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 428 BP 123S EP 123S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000421 ER PT J AU Ha, KS Poole, J Deicken, RF Pegues, MP Eliaz, Y Chosiad, L Vinogradov, S AF Ha, KS Poole, J Deicken, RF Pegues, MP Eliaz, Y Chosiad, L Vinogradov, S TI Decreased total intracranial volume in schizophrenia and its implication SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Seoul Natl Univ, Dept Psychiat, Seoul, South Korea. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 435 BP 125S EP 125S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000428 ER PT J AU Wirshing, DA Wirshing, W Gonzalez, L Rossotto, E Watson, J Pierre, JM Kern, RS Hwang, S Ballon, J Pien, J AF Wirshing, DA Wirshing, W Gonzalez, L Rossotto, E Watson, J Pierre, JM Kern, RS Hwang, S Ballon, J Pien, J TI The community re-entry program for schizophrenia: Neurocognitive and psychopathologic correlates of treatment response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 455 BP 131S EP 131S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000448 ER PT J AU Kemether, EM Buchsbaum, MS Hazlett, E Shinwari, A Mitropoulou, V Siever, LJ Byne, WM AF Kemether, EM Buchsbaum, MS Hazlett, E Shinwari, A Mitropoulou, V Siever, LJ Byne, WM TI Assessment of thalamic mediodorsal nucleus and pulvinar using magnetic resonance imaging in schizophrenia spectrum disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 459 BP 132S EP 132S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000452 ER PT J AU Spence, KM Niznikiewicz, MA Nestor, PG McCarley, RW AF Spence, KM Niznikiewicz, MA Nestor, PG McCarley, RW TI Attention and laterality effects on the 40-Hz auditory response in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Cambridge, MA 02138 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 460 BP 132S EP 133S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000453 ER PT J AU Elman, J Karlsgodt, KH Krause, S Breiter, HC Gastfriend, DR AF Elman, J Karlsgodt, KH Krause, S Breiter, HC Gastfriend, DR TI Laboratory-based cocaine administration in human subjects: Ethical dilemmas and clinical outcomes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Addict Res Program, Boston, MA USA. MENC, Boston, MA USA. RI Karlsgodt, Katherine/H-2964-2013 OI Karlsgodt, Katherine/0000-0003-3332-4231 NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 472 BP 136S EP 137S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000465 ER PT J AU Breiter, HC AF Breiter, HC TI The generalized human circuitry of brain reward and its functional dissection SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MENC, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 473 BP 137S EP 137S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000466 ER PT J AU Karlsgodt, KH Gastfriend, DR Roman, JS Elman, I AF Karlsgodt, KH Gastfriend, DR Roman, JS Elman, I TI Gender differences in cocaine craving among non-treatment seeking individuals with cocaine dependence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. MENC, Boston, MA USA. Addict Res Program, Boston, MA USA. RI Karlsgodt, Katherine/H-2964-2013 OI Karlsgodt, Katherine/0000-0003-3332-4231 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 475 BP 137S EP 137S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000468 ER PT J AU Roman, JS Gastfriend, DR Breiter, HC Karlsgodt, KH Elman, I AF Roman, JS Gastfriend, DR Breiter, HC Karlsgodt, KH Elman, I TI Clinical correlates of physiologic cocaine responses SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Addict Res Program, Boston, MA USA. MENC, Boston, MA USA. RI Karlsgodt, Katherine/H-2964-2013 OI Karlsgodt, Katherine/0000-0003-3332-4231 NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 474 BP 137S EP 137S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000467 ER PT J AU Gastfriend, DR Karlsgodt, KH Elman, I AF Gastfriend, DR Karlsgodt, KH Elman, I TI Importance of sample clinical characteristics in cocaine research SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Addict Res Program, Boston, MA USA. MENC, Boston, MA USA. RI Karlsgodt, Katherine/H-2964-2013 OI Karlsgodt, Katherine/0000-0003-3332-4231 NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 476 BP 138S EP 138S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000469 ER PT J AU Fava, M Schmidt, ME Zhang, S Gonzales, J Raute, N Judge, R AF Fava, M Schmidt, ME Zhang, S Gonzales, J Raute, N Judge, R TI Response to re-initiation of fluoxetine treatment by patients relapsing during long term treatment of depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 547 BP 159S EP 160S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000540 ER PT J AU Schmidt, ME Bergstrom, R Fava, M Zhang, S Gonzales, JS Raute, NA Judge, R AF Schmidt, ME Bergstrom, R Fava, M Zhang, S Gonzales, JS Raute, NA Judge, R TI Response to an increased dose of fluoxetine by patients relapsing during long-term treatment of depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Lilly Res Labs, Indianapolis, IN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 558 BP 163S EP 163S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000550 ER PT J AU Leonard, S Gault, J Hopkins, J Logel, J Vianzon, R Drebing, C Short, M Walton, K Berger, R Ross, R Olincy, A Adler, L Freedman, R AF Leonard, S Gault, J Hopkins, J Logel, J Vianzon, R Drebing, C Short, M Walton, K Berger, R Ross, R Olincy, A Adler, L Freedman, R TI DNA variants in the alpha 7 nicotinic receptor gene promoter are associated with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Boulder, CO 80309 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Boulder, CO 80309 USA. Denver Vet Affairs Med Res Ctr, Denver, CO USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 571 BP 166S EP 166S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000562 ER PT J AU Yao, JK Leonard, S Reddy, RD AF Yao, JK Leonard, S Reddy, RD TI Increased level of mercaptans in postmortem brains from schizophrenic patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 591 BP 172S EP 172S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000582 ER PT J AU Wirshing, DA Boyd, J Meng, L Ballon, J Wirshing, WC AF Wirshing, DA Boyd, J Meng, L Ballon, J Wirshing, WC TI Antipsychotic medication: Impact on coronary artery disease risk factors SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 604 BP 175S EP 176S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000595 ER PT J AU Barber, DL Beattie, BK Mason, JM Nguyen, MHH Yoakim, M Neel, BG D'Andrea, AD Frank, DA AF Barber, DL Beattie, BK Mason, JM Nguyen, MHH Yoakim, M Neel, BG D'Andrea, AD Frank, DA TI A common epitope is shared by activated signal transducer and activator of transcription-5 (STAT5) and the phosphorylated erythropoietin receptor: implications for the docking model of STAT activation SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; PHENYLHYDRAZINE-TREATED MICE; TYROSINE PHOSPHORYLATION; GROWTH-HORMONE; DNA-BINDING; HEMATOPOIETIC-CELLS; INTRACELLULAR DOMAIN; MULTIPLE CYTOKINES; JAK-STAT5 PATHWAY; DEPENDENT GROWTH AB Erythropoietin (EPO) specifically activates the Janus kinase JAK2 and the transcription factor signal transducer and activator of transcription-5 (STAT5). All members of the STAT family are tyrosine phosphorylated in response to cytokine stimulation at a conserved carboxy-terminal tyrosine, Y694, in the case of STAT5. To determine structural features important for STAT signaling, we generated an activation-specific STAT5 antibody using a phosphopeptide containing amino acids 687 to 698 of STAT5 as antigen. This antibody specifically recognizes tyrosine-phosphorylated STAT5 but not nonphosphorylated STAT5. In immunoprecipitation reactions from cell lines and primary erythroblasts, 2 distinct polyclonal activation-specific STAT5 antibodies selectively immunoprecipitate the tyrosine phosphorylated EPO receptor (EPO-R) in addition to STAT5 under native and denaturing conditions. We propose that the activation-specific STAT5 antibody recognizes the 2 substrates to which the STAT5 SH2 domain interacts, namely, the tyrosine-phosphorylated EPO-R and STAT5 itself. Several studies have implicated EPO-R Y343, Y401, Y431, and Y479 in the recruitment of STAT5. Using a series of EPO-R tyrosine mutants expressed in Ba/F3 cells, we have shown that the activation-specific STAT5 antibody immunoprecipitates an EPO-R containing only 2 tyrosines at positions 343 and 401, confirming the importance of these tyrosines in STAT5 recruitment. These data uncover a novel aspect of STAT SH2 domain recognition and demonstrate the utility of activation-specific antibodies for examining the specificity of STAT-cytokine receptor interactions. (Blood. 2001;97:2230-2237) (C) 2001 by The American Society of Hematology. C1 Ontario Canc Inst, Div Cellular & Mol Biol, Toronto, ON, Canada. Toronto Gen Hosp, Dept Lab Med & Pathobiol, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. Beth Israel Deaconess Med Ctr, Canc Biol Program, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Barber, DL (reprint author), Ontario Canc Inst, Div Cellular & Mol Biol, 610 Univ Ave, Toronto, ON, Canada. FU NCI NIH HHS [CA 79547]; NIDDK NIH HHS [DK 50693, F32 DK 09465] NR 72 TC 30 Z9 32 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2001 VL 97 IS 8 BP 2230 EP 2237 DI 10.1182/blood.V97.8.2230 PG 8 WC Hematology SC Hematology GA 429KN UT WOS:000168516100006 PM 11290583 ER PT J AU Okuda, K Weisberg, E Gilliland, DG Griffin, JD AF Okuda, K Weisberg, E Gilliland, DG Griffin, JD TI ARG tyrosine kinase activity is inhibited by ST1571 SO BLOOD LA English DT Article ID ABL-RELATED GENE; CHRONIC MYELOMONOCYTIC LEUKEMIA; HEMATOPOIETIC-CELL LINES; CHRONIC MYELOID-LEUKEMIA; BCR-ABL; SIGNALING PATHWAYS; ETV6/ABL FUSION; POSITIVE CELLS; TEL-ABL; PROTEIN AB The tyrosine kinase inhibitor STI571 inhibits BCR/ABL and induces hematologic remission in most patients with chronic myeloid leukemia. In addition to BCR/ABL, STI571 also inhibits v-Abl, TEL/ABL, the native platelet-derived growth factor (PDGF)beta receptor, and c-KIT, but it does not inhibit SRC family kinases, c-FMS, FLT3, the epidermal growth factor receptor, or multiple other tyrosine kinases. ARG is a widely expressed tyrosine kinase that shares substantial sequence identity with c-ABL in the kinase domain and cooperates with ABL to regulate neurulation in the developing mouse embryo. As described here, ARG has recently been implicated in the pathogenesis of leukemia as a fusion partner of TEL. A TEL/ARG fusion was constructed to determine whether ARG can be inhibited by STI571. When expressed in the factor-dependent murine hematopoietic cell line Ba/F3, the TEL/ARG protein was heavily phosphorylated on tyrosine, increased tyrosine phosphorylation of multiple cellular proteins, end induced factor-independent proliferation. The effects of STI571 on Ba/F3 cells transformed with BCR/ABL, TEL/ABL, TEL/PDGF betaR, or TEL/ARG were then compared, STI571 inhibited tyrosine phosphorylation end cell growth of Ba/F3 cells expressing BCR/ABL, TEL/ABL, TEL/PDGF betaR, and TEL/ARG with an IC50 of approximately 0.5 muM in each case, but it had no effect on untransformed Ba/F3 cells growing in IL-3 or on Ba/F3 cells transformed by TEL/ JAK2. Culture of TEL/ARG-transfected Ba/F3 cells with IL-3 completely prevented STI571-induced apoptosis in these cells, similar to what has been observed with BCR/ABL- or TEL/ABL-transformed cells. These results indicate that ARG is a target of the small molecule, tyrosine kinase inhibitor STI571. (Blood. 2001;97: 2440-2448) (C) 2001 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 39 TC 195 Z9 208 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2001 VL 97 IS 8 BP 2440 EP 2448 DI 10.1182/blood.V97.8.2440 PG 9 WC Hematology SC Hematology GA 429KN UT WOS:000168516100032 PM 11290609 ER PT J AU Kulke, MH Thakore, KS Thomas, G Wang, H Loda, M Eng, C Odze, RD AF Kulke, MH Thakore, KS Thomas, G Wang, H Loda, M Eng, C Odze, RD TI Microsatellite instability and hMLH1/hMSH2 expression in Barrett esophagus-associated adenocarcinoma SO CANCER LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-27, 1999 CL SAN FRANCISCO, CALIFORNIA SP US & Canadian Acad Pathol DE esophageal adenocarcinoma; Barrett esophagus; microsatellite instability; hMSH2; hMLH1 ID NONPOLYPOSIS COLORECTAL-CANCER; REPLICATION ERROR PHENOTYPE; MISMATCH REPAIR GENES; GASTRIC-CANCER; ENDOMETRIAL CARCINOMA; CLINICOPATHOLOGICAL VARIABLES; PROMOTER HYPERMETHYLATION; GENOMIC INSTABILITY; ALTERED EXPRESSION; FAMILY HISTORY AB BACKGROUND, Microsatellite instability (MSI) has been documented in malignancies associated with hereditary nonpolyposis colon carcinoma and in sporadic malignancies of the colon, stomach, and endometrium. In these malignancies, MSI is associated with defects in the DNA mismatch repair enzymes hMSH2 and hMLH1. Defects in these enzymes result in a phenotype characterized by instability of multiple microsatellite repeat sequences throughout the genome. This study sought to determine the prevalence of MSI in 80 primary Barrett esophagus-associated adenocarcinomas (BEAd) and to examine the relation of MSI with the clinical and pathologic features of the tumors. METHODS. Eighty BEAd were evaluated for the presence of MSI by using the microsatellite markers BAT25, BAT26, D10S219, D10S541, and D10S551. These tumors also were evaluated for immunohistochemical expression of hMSH2 and hMLH1. RESULTS. High levels of MSI were not found in any of the tumors examined. Furthermore, immunohistochemical expression of hMSH2 and hMLH1 was retained in all cases evaluated. Evidence of low level MSI was found in 16% of tumors. In none of these tumors, however, was MSI present in more than two of five loci. The presence of MSI did not correlate with patient age, tumor stage, degree of differentiation, or with patient survival. CONCLUSIONS. High level MSI and loss of hMLH1/hMSH2 expression is uncommon in BEAd. A subset of BEAd demonstrate low level MSI. The presence of low level MSI was not associated with the clinicopathologic features of the tumors examined. Cancer 2001;91:1451-7, (C) 2001 American Cancer Society. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Ohio State Univ, Human Canc Genet Program, Columbus, OH 43210 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [P30CA16058] NR 39 TC 32 Z9 37 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 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2001 VL 91 IS 8 BP 1451 EP 1457 DI 10.1002/1097-0142(20010415)91:8<1451::AID-CNCR1152>3.0.CO;2-Z PG 7 WC Oncology SC Oncology GA 421UD UT WOS:000168081200007 PM 11301392 ER PT J AU Kim, DH Nelson, HH Wiencke, JK Zheng, SC Christiani, DC Wain, JC Mark, EJ Kelsey, KT AF Kim, DH Nelson, HH Wiencke, JK Zheng, SC Christiani, DC Wain, JC Mark, EJ Kelsey, KT TI p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer SO CANCER RESEARCH LA English DT Article ID DE-NOVO METHYLATION; DNA METHYLATION; ABERRANT METHYLATION; SIGNALING PATHWAY; GENE PROMOTER; CYCLE CONTROL; EARLY EVENT; P18 GENES; EXPRESSION; P53 AB The p16(INK4a) protein inhibits cyclin-dependent kinase 4, a key regulator of progression through the G, phase of the cell cycle. Methylation of CpG islands in the promoter region is an important avenue for inactivation of p16. The mechanism of methylation of the p16 promoter region, however, has not been elucidated. Recent reports investigating p16 methylation in non-small cell lung cancer (NSCLC) suggest that carcinogens in tobacco smoke induce the DNA methylation process. We investigated the association between methylation of the p16 promoter region and exposure to tobacco smoke in 185 primary NSCLCs. We also studied the relationship of p16 methylation with mutation of the K-ras and p53 genes, as well as with methylation at the DAP-kinase and p14(ARF) loci. Finally, we evaluated the prognostic significance of p16 methylation in NSCLC, The prevalence of p16 methylation was greater in squamous cell carcinoma (41%) compared with adenocarcinoma (22%; P = 0.03; Fisher's exact test). Methylation of p16 was significantly associated with pack-years smoked (P = 0.007; Wilcoxon rank sum test), duration of smoking (P = 0.0009; Wilcoxon rank sum test), and negatively with the time since quitting smoking (P = 0.03; Wilcoxon rank sum test). No methylation of the nearby p14(ARF) locus was detected, and methylation of the DAP-kinase locus was not associated with either p16 methylation or with exposure to tobacco smoke. In patients with stage 1 adenocarcinoma, p16 methylation was an independent risk factor predicting significantly shorter postsurgery survival (P = 0.03), controlling for the significant effects of other factors, including K-ras mutation. These findings suggest that methylation of CpG islands in tobacco-associated cancers occurs in a gene- and tissue-specific manner and is induced directly or indirectly by exposure to tobacco smoke in NSCLC. C1 Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, Lab Mol Epidemiol, San Francisco, CA 94143 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, 665 Huntington Ave,Bldg 1,Room 207, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014 FU NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES 08357, ES/CA 06409, ES06717] NR 53 TC 261 Z9 274 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2001 VL 61 IS 8 BP 3419 EP 3424 PG 6 WC Oncology SC Oncology GA 424CR UT WOS:000168215000033 PM 11309302 ER PT J AU Olson, DP Taylor, BJ Ivy, SP AF Olson, DP Taylor, BJ Ivy, SP TI Detection of MRP functional activity: Calcein AM but not BCECF AM as a multidrug resistance-related protein (MRP1) substrate SO CYTOMETRY LA English DT Article DE pediatric leukemia; chemotherapy resistance; MDR; MRP; flow cytometry ID HUMAN TUMOR-CELLS; P-GLYCOPROTEIN; HEMATOLOGIC MALIGNANCIES; LEUKEMIA-CELLS; CANCER-CELLS; GENE MRP1; EXPRESSION; LINES; EFFLUX; CHEMORESISTANCE AB Resistance to anticancer drugs has been attributed to an array of cellular changes. The multidrug resistance-related protein (MRP1) is an efflux pump whose overexpression confers resistance to several classes of drugs, such as the anthracyclines, epipodophyllotoxins, and vinca alkaloids, These drugs are mainstays in cancer therapy. MRP1 overexpression is hypothesized to be a causative agent of clinical treatment failure. Consistently accurate methods for detecting this protein are necessary to further understand its biology and delineate its possible clinical relevance, Flow cytometric analysis of multidrug resistance (MDR) is a valuable method to evaluate both antigen expression and function, Using flow cytometry, we assayed MRP1 functional activity in pediatric leukemic blasts and an array of MDR+ and WT cell lines, We conclude that calcein AM, when used in a retention assay with MRP1-specific modulators, is able to reliably detect MRP functional activity. 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF AM) transport is not indicative of MRP1 overexpression. (C) 2001 Wiley-Liss, Inc. C1 Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. RP Olson, DP (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, 149 13th St,Room 5212, Boston, MA 02129 USA. NR 29 TC 38 Z9 39 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 0196-4763 J9 CYTOMETRY JI Cytometry PD APR 15 PY 2001 VL 46 IS 2 BP 105 EP 113 DI 10.1002/cyto.1072 PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 430BB UT WOS:000168552700007 PM 11309820 ER PT J AU Sun, YJ Wyatt, RT Bigley, A Krontiris, TG AF Sun, YJ Wyatt, RT Bigley, A Krontiris, TG TI Expression and replication timing patterns of wildtype and translocated BCL2 genes SO GENOMICS LA English DT Article ID MATRIX ATTACHMENT REGIONS; MAJOR BREAKPOINT REGION; HEAVY-CHAIN LOCUS; BETA-GLOBIN GENE; NUCLEAR MATRIX; C-MYC; CHROMOSOMAL TRANSLOCATION; FOLLICULAR LYMPHOMA; INTERPHASE NUCLEI; BURKITTS-LYMPHOMA AB Translocation of the BCL2 gene from chromosome 18 to hromosome 14 results in constitutive expression of the gene. We have recently demonstrated that the major breakpoint region (mbr) of BCL2, which is implicated in 70% of t(14;18) translocations present in human follicular lymphoma, is a matrix attachment region. Since these regions are implicated in control of both transcription and replication, we wished to determine whether BCL2 translocation was also accompanied by changes in replication timing of the translocated allele, Using both fluorescence in situ hybridization and allele-specific PCR, we have demonstrated that the translocated allele replicates at the G1/S boundary, while the wildtype allele continues to replicate as usual in mid-S phase. These differences are accompanied by allele-specific changes in BCL2 expression. Since the net structural effect of t(14;18) translocations within the mbr is to disrupt the BCL2 MAR and replace it with the IGH MARs located just downstream of each breakpoint, we conclude that MAR exchange is a significant, selectable outcome of these translocations. We propose that subsequent changes of replication and transcriptional patterns for the translocated BCL2 allele result from this exchange and represent important early steps in lymphomagenesis, (C) 2001 Academic Press. C1 City Hope Natl Med Ctr, Div Mol Med, Beckman Res Inst, Duarte, CA 91010 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Krontiris, TG (reprint author), City Hope Natl Med Ctr, Div Mol Med, Beckman Res Inst, 1450 E Duarte Rd, Duarte, CA 91010 USA. FU NCI NIH HHS [CA51985] NR 46 TC 15 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 2001 VL 73 IS 2 BP 161 EP 170 DI 10.1006/geno.2000.6479 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 428DU UT WOS:000168446700004 PM 11318606 ER PT J AU Acierno, JS Kennedy, JC Falardeau, JL Leyne, M Bromley, MC Colman, MW Sun, M Bove, C Ashworth, LK Chadwick, LH Schiripo, T Ma, S Goldin, E Schiffmann, R Slaugenhaupt, SA AF Acierno, JS Kennedy, JC Falardeau, JL Leyne, M Bromley, MC Colman, MW Sun, M Bove, C Ashworth, LK Chadwick, LH Schiripo, T Ma, S Goldin, E Schiffmann, R Slaugenhaupt, SA TI A physical and transcript map of the MCOLN1 gene region on human chromosome 19p13.3-p13.2 SO GENOMICS LA English DT Article ID MUCOLIPIDOSIS TYPE-IV; MUTATIONS; 19P; IDENTIFICATION; FAMILIES; LOCUS; DISEASE AB Mutations in IMCOLN1 have been found to cause mucolipidosis type IV (MLIV; MIM 252650), a rare autosomal recessive lysosomal storage disorder found primarily in the Ashkenazi Jewish population. As a part of the successful cloning of MCOLN1, we constructed a 1.4-Mb physical map containing 14 BACs and 4 cosmids that encompasses the region surrounding MCOLN1 on human chromosome 19p13.3-p13.2-a region to which linkage or association has been reported for multiple diseases. Here we detail the precise physical mapping of 28 expressed sequence tags that represent unique UniGene clusters, of which 15 are known genes. We present a detailed transcript map of the MCOLN1 gene region that includes the genes KIAA0521, neuropathy target esterase (NTE), a novel zinc finger gene, and two novel transcripts in addition to MCOLN1. We also report the identification of eight new polymorphic markers between D19S406 and D19S912, which allowed us to pinpoint the location of MCOLN1 by haplotype analysis and which will facilitate future fine-mapping in this region, Additionally, we briefly describe the correlation between the observed haplotypes and the mutations found in MCOLN1. The complete 14-marker haplotypes of non-Jewish disease chromosomes, which are crucial for the genetic diagnosis of MLIV in the non-Jewish population, are presented here for the first time. (C) 2001 Academic Press. C1 Harvard Univ, Inst Human Genet, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Lawrence Livermore Natl Lab, Human Genome Ctr, Livermore, CA 94550 USA. RP Slaugenhaupt, SA (reprint author), Harvard Univ, Inst Human Genet, Sch Med, HIM Bldg,Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NINDS NIH HHS [R01-NS39945] NR 23 TC 6 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 2001 VL 73 IS 2 BP 203 EP 210 DI 10.1006/geno.2001.6526 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 428DU UT WOS:000168446700008 PM 11318610 ER PT J AU Kornblith, AB AF Kornblith, AB TI Does palliative care palliate? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID QUALITY-OF-LIFE; STAGE BREAST-CANCER; ADJUVANT THERAPY; QUESTIONNAIRE; PREFERENCES; SCORES; WOMEN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kornblith, AB (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 21 TC 7 Z9 8 U1 9 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2001 VL 19 IS 8 BP 2111 EP 2113 PG 3 WC Oncology SC Oncology GA 423LT UT WOS:000168178300001 PM 11304762 ER PT J AU Schiller, JH Adak, S Cella, D DeVore, RF Johnson, DH AF Schiller, JH Adak, S Cella, D DeVore, RF Johnson, DH TI Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593 - A phase III trial of the Eastern Cooperative Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MAINTENANCE CHEMOTHERAPY; TOPOISOMERASE-II; CYCLOPHOSPHAMIDE; DOXORUBICIN; VINCRISTINE; THERAPY AB Purpose: To determine the efficacy of topotecan in combination with standard chemotherapy in previously untreated patients with extensive-stage small-cell lung cancer (SCLC), the Eastern Cooperative Oncology Group (ECOG) conducted a phase III trial. Patients and Methods: Eligible patients had measurable or assessable disease and an ECOG performance status of 0 to 2; stable brain metastases were allowed. All patients received four cycles of cisplatin and etoposide every 3 weeks (step 1; PE). Patients with stable or responding disease were then randomized to observation or four cycles of topatecan (1.5 mg/m(2)/d for 5 days, every 3 weeks; step 2). A total of 402 eligible patients were registered to step 1, and 223 eligible patients were registered to step 2 (observation, n = 111; topatecan, n = 112). Results: Complete and partial response rates to induction PE were 3% and 32%, respectively. A 7% response rate was observed with topotecan (complete response, 2%; partial response, 5%). The median survival time for all 402 eligible patients was 9.6 months. Progression-free survival (PFS) from date of randomization on step 2 was significantly better with topotecan compared with observation (3.6 months v 2.3 months; P < .001). However, overall survival from date of randomization on step 2 was not significantly different between the observation and topotecan arms (8.9 months v 9.3 months; P = .43), Grade 4 neutropenia and thrombocytapenia occurred in 50% and 3%, respectively, of PE patients in step 1 and 60% and 13% of topotecan patients in step 2, Grade 4/5 infection was observed in 4.6% of PE patients and 1.8% of topotecan patients, Grade 3/4 anemia developed in 22% of patients who received topotecan. No difference in quality of life between topatecan and observation was observed at any assessment time or for any of the subscale scores. Conclusion: Four cycles of PE induction therapy followed by four cycles of topatecan improved PFS but failed to improve overall survival or quality of life in extensive-stage SCLC, Four cycles of standard PE remains an appropriate first-line treatment for extensive-stage SCLC patients with good performance status. <(c)> 2001 by American Society of Clinical Oncology. C1 Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Evanston Northwestern Healthcare, Evanston, IL USA. Northwestern Univ, Evanston, IL USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. RP Schiller, JH (reprint author), Univ Wisconsin Hosp & Clin, 600 Highland Ave,Rm K4-636, Madison, WI 53792 USA. RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA21076, CA21115, CA23318, CA49957, CA66636] NR 31 TC 167 Z9 177 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2001 VL 19 IS 8 BP 2114 EP 2122 PG 9 WC Oncology SC Oncology GA 423LT UT WOS:000168178300002 PM 11304763 ER PT J AU Shen, HM Cheng, T Olszak, I Garcia-Zepeda, E Lu, ZJ Herrmann, S Fallon, R Luster, AD Scadden, DT AF Shen, HM Cheng, T Olszak, I Garcia-Zepeda, E Lu, ZJ Herrmann, S Fallon, R Luster, AD Scadden, DT TI CXCR-4 desensitization is associated with tissue localization of hemopoietic progenitor cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC STEM-CELLS; CHEMOKINE RECEPTOR CXCR4; FACTOR-I; CHEMOATTRACTANT; EXPRESSION; TYPE-1; SDF-1; RESENSITIZATION; ENGRAFTMENT AB The chemokine stroma-derived factor (SDF)-1, and its receptor, CXCR-4, have been shown to be essential for the translocation of hemopoietic stern cells from the fetal liver to the bone marrow (BM). We hypothesized that if CXCR-4 plays a crucial role in the localization of human hemopoiesis, stem cells from distinct tissue sources should demonstrate distinct CXCR-4 expression or signaling profiles. CD34(+) cells from BM were compared with blood: either mobilized peripheral blood or umbilical cord blood. Unexpectedly, significantly higher levels of CXCR-4 surface expression on CD34(+) cells from blood sources, mobilized peripheral blood, or cord blood were observed compared with BM (p = 0.0005 and p = 0.002, respectively). However, despite lower levels of CXCR-4, responsiveness of the cells to SDF-1 as measured by either calcium flux or transmigration was proportionally greatest in cells derived from BM. Further, internalization of CXCR-4 in response to ligand, associated with receptor desensitization, was significantly lower on BM-derived cells. Therefore, preserved chemokine receptor signaling was highly associated with marrow rather than blood localization. To test the functional effects of perturbing CXCR-4 signaling, adult mice were exposed to the niethionine-SDF-1 beta analog that induces prolonged down-regulation/desensitization of CXCR-4 and observed mobilization of Lin(-), Sca-1(+), Thy-1(low), and c-kit(+) hemopoietic progenitor cells to the peripheral blood with a > 30-fold increase compared with PBS control (p = 0.0007 day 1 and p = 0.004 day 2). These data demonstrate that CXCR-4 expression and function can be dissociated in progenitor cells and that desensitization of CXCR-4 induces stem cell entry into the circulation. The Journal of Immunology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr,Canc Ctr, Boston, MA 02129 USA. St Louis Univ, St Louis, MO 63103 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr,Canc Ctr, 149 13th St,Room 5212, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL55718, HL44851]; NIDDK NIH HHS [DK50234] NR 26 TC 114 Z9 116 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2001 VL 166 IS 8 BP 5027 EP 5033 PG 7 WC Immunology SC Immunology GA 471VA UT WOS:000170948300031 PM 11290783 ER PT J AU Appel, H Seth, NP Gauthier, L Wucherpfennig, KW AF Appel, H Seth, NP Gauthier, L Wucherpfennig, KW TI Anergy induction by dimeric TCR ligands SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; MYELIN BASIC-PROTEIN; CLASS-II MOLECULES; CRYSTALLOGRAPHIC EVIDENCE; ERYTHROPOIETIN RECEPTOR; MULTIPLE-SCLEROSIS; STRUCTURAL BASIS; CELIAC-DISEASE; SELF-PEPTIDES; ACTIVATION AB T cells that recognize particular self Ags are thought to be important in the pathogenesis of autoimmune diseases. In multiple sclerosis, susceptibility is associated with HLA-DR2, which can present myelin-derived peptides to CD4(+) T cells. To generate molecules that target such T cells based on the specificity of their TCR, we expressed a soluble dimeric DR2-IgG fusion protein with a bound peptide from myelin basic protein (MBP). Soluble, dimeric DR2/MBP peptide complexes activated MBP-specific T cells in the absence of signals from costimulatory or adhesion molecules. This initial signaling through the TCR rendered the T cells unresponsive (anergic) to subsequent activation by peptide-pulsed APCs. Fluorescent labeling demonstrated that anergic T cells were initially viable, but became susceptible to late apoptosis due to insufficient production of cytokines. Dimerization of the TCR with bivalent MHC class II/peptide complexes therefore allows the induction of anergy inhuman CD4(+) T cells with a defined MHC/peptide specificity. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. FU NIAID NIH HHS [P01 AI045757, AI 45757]; NINDS NIH HHS [NS39096, R01 NS039096] NR 44 TC 36 Z9 38 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2001 VL 166 IS 8 BP 5279 EP 5285 PG 7 WC Immunology SC Immunology GA 471VA UT WOS:000170948300062 PM 11290814 ER PT J AU Garcia-Anoveros, J Samad, TA Zuvela-Jelaska, L Woolf, CJ Corey, DR AF Garcia-Anoveros, J Samad, TA Zuvela-Jelaska, L Woolf, CJ Corey, DR TI Transport and localization of the DEG/ENaC ion channel BNaC1 alpha to peripheral mechanosensory terminals of dorsal root ganglia neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE DEG/ENaC channels; mechanosensory; mechanotransduction; touch; nociception; dorsal root ganglion; unidirectional transport; degenerin ID EPITHELIAL NA+ CHANNEL; ACID-EVOKED CURRENTS; SENSORY NEURONS; CAENORHABDITIS-ELEGANS; CAPSAICIN RECEPTOR; MOLECULAR-CLONING; MYSTACIAL PAD; HAIRY SKIN; RAT SKIN; PGP 9.5 AB Mammalian brain sodium channel (BNaC, also known as BNC/ ASlC) proteins form acid-sensitive and amiloride-blockable sodium channels that are related to putative mechanosensory channels. Certain BNaC isoforms are expressed exclusively in dorsal root ganglia (DRG) and have been proposed to form the ion channels mediating tissue acidosis-induced pain. With antibody labeling, we find that the BNaC1 alpha isoform is expressed by most large DRG neurons (low-threshold mechanosensors not involved in acid-induced nociception) and few small nociceptor neurons (which include high-threshold mechanoreceptors). BNaC1 alpha is transported from DRG cell bodies to sensory terminals in the periphery, but not to the spinal cord, and is located specifically at specialized cutaneous mechanosensory terminals, including Meissner, Merkel, penicillate, reticular, lanceolate, and hair follicle palisades as well as some intraepidermal and free myelinated nerve endings. Accordingly, BNaC1 alpha channels might participate in the transduction of touch and painful mechanical stimuli. 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. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Garcia-Anoveros, J (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. OI Corey, David/0000-0003-4497-6016 FU NINDS NIH HHS [NS38253-01] NR 54 TC 162 Z9 173 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2001 VL 21 IS 8 BP 2678 EP 2686 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 420GU UT WOS:000167997900016 PM 11306621 ER PT J AU Gutkind, D Ventura, J Barr, C Shaner, A Green, M Mintz, J AF Gutkind, D Ventura, J Barr, C Shaner, A Green, M Mintz, J TI Factors affecting reliability and confidence of DSM-III-R psychosis-related diagnosis SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; bipolar disorder; schizotypal personality; schizoaffective disorder; substance-induced psychotic disorders ID BIZARRE DELUSIONS; QUALITY ASSURANCE AB The relationships between interrater diagnostic reliability, confidence in diagnosis, DSM-III-R criteria ambiguity and case report data quality were examined in 20 case vignettes describing psychosis-related symptomatology. Each of seven diagnosticians made DSM-III-R diagnoses and gave confidence ratings for those diagnoses, as well as ratings on quality of data presented and clarity of diagnostic criteria for each vignette. As hypothesized, confidence ratings significantly predicted interrater diagnostic agreement. Clarity of DSM-III-R criteria positively correlated with both interrater reliability and confidence. Case report data quality correlated with diagnostic confidence but, contrary to the authors' hypothesis, did not correlate with interrater agreement. The authors conclude that confidence ratings may be useful indices of diagnostic reliability among experienced clinicians and suggest that the case report method allows fur reliable diagnoses to be made. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Ctr Res Treatment & Rehabil Psychosis, Los Angeles, CA 90073 USA. RP Ventura, J (reprint author), Univ Calif Los Angeles, Dept Psychiat, Ctr Res Treatment & Rehabil Psychosis, 300 Med Plaza,Room 2243, Los Angeles, CA 90095 USA. NR 7 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 15 PY 2001 VL 101 IS 3 BP 269 EP 275 DI 10.1016/S0165-1781(01)00223-2 PG 7 WC Psychiatry SC Psychiatry GA 429CB UT WOS:000168497500008 PM 11311930 ER PT J AU Tapp, A Wood, AE Kilzieh, N Erdmann, JM AF Tapp, A Wood, AE Kilzieh, N Erdmann, JM TI Depressive symptoms, cognition, and functional outcome in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, MIRECC, Amer Lake Div, Tacoma, WA 98493 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 23 EP 23 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700072 ER PT J AU Yao, JK Leonard, SS Reddy, RD AF Yao, JK Leonard, SS Reddy, RD TI Increased nitric oxide radicals in postmortem brains from schizophrenic patients SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 58 EP 58 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700191 ER PT J AU Freedman, R Leonard, SS AF Freedman, R Leonard, SS TI Chromosome 15q linkage for schizophrenia in the NIMH genetics initiative families SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 Univ Colorado, Denver, CO 80262 USA. Denver VAMC, Denver, CO 80262 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 70 EP 70 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700230 ER PT J AU Kee, KS Holaway, RM Kuo, JR Green, MF AF Kee, KS Holaway, RM Kuo, JR Green, MF TI Emotional processing deficits in schizophrenia: Relationship to social adjustment and familial vulnerability SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs, MIRECC, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 111 EP 111 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700369 ER PT J AU Wood, AE Secrest, LL Tapp, A AF Wood, AE Secrest, LL Tapp, A TI Cognition, psychiatric symptoms, and dimensions of community functioning in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 MIRECC, Amer Lake Div A116, VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 124 EP 125 PG 2 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700418 ER PT J AU Secrest, LL Wood, AE Tapp, A Cubberley, L AF Secrest, LL Wood, AE Tapp, A Cubberley, L TI Use of the Allen Cognitive Level Test as an estimate of comunity functioning in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 144 EP 145 PG 2 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700486 ER PT J AU McCarley, RW Dickey, CC Fraone, S Niznikiewicz, MA Hirayasu, Y Voglmaier, MM Shenton, ME AF McCarley, RW Dickey, CC Fraone, S Niznikiewicz, MA Hirayasu, Y Voglmaier, MM Shenton, ME TI Reduced left Heschl's gyrus volume in schizophrenia spectrum disorder using structural MRI SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 160 EP 161 PG 2 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700542 ER PT J AU Pierre, JM Wirshing, DA Marder, SR Saunders, CS Wirshing, WC AF Pierre, JM Wirshing, DA Marder, SR Saunders, CS Wirshing, WC TI Sexual side effects of novel antipsychotic medications SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 289 EP 289 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700982 ER PT J AU Wirshing, DA Boyd, J Meng, L Ballon, J Champion, K Wirshing, WC AF Wirshing, DA Boyd, J Meng, L Ballon, J Champion, K Wirshing, WC TI Antipsychotic medication: Impact on coronary artery disease risk factors SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 291 EP 291 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700988 ER PT J AU Hirshkowitz, M Schwartz, J Corser, B Sahota, P AF Hirshkowitz, M Schwartz, J Corser, B Sahota, P TI Long-term (136 weeks) safety and efficacy of modafinil for the treatment of excessive daytime sleepiness associated with narcolepsy SO SLEEP LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Integris Sleep Disorders Ctr Oklahoma, Oklahoma City, OK USA. Community Res Management Assoc, Cincinnati, OH USA. Univ Missouri, Columbia, MO USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 577 BP A329 EP A330 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900576 ER PT J AU Nienhuis, R Moore, RY Thannickal, TC Siegel, JM AF Nienhuis, R Moore, RY Thannickal, TC Siegel, JM TI Morphology of hypocretin neurons in human narcolepsy SO SLEEP LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 154 BP A95 EP A95 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900156 ER PT J AU Ross, RJ Book, HW Sanford, LD Silver, SM Ford, NM Huff, RM Morrison, AR AF Ross, RJ Book, HW Sanford, LD Silver, SM Ford, NM Huff, RM Morrison, AR TI REM activity increase in PTSD does not depend on a depressive diathesis and alcoholism SO SLEEP LA English DT Meeting Abstract C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 191 BP A118 EP A118 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900193 ER PT J AU Sanford, LD Tang, X Ross, RJ Morrison, AR AF Sanford, LD Tang, X Ross, RJ Morrison, AR TI Influence of anticipatory anxiety on sleep in behaviorally "anxious" and "non-anxious" mice SO SLEEP LA English DT Meeting Abstract C1 Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 84 BP A53 EP A54 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900086 ER PT J AU Tang, X Ross, RJ Morrison, AR Sanford, LD AF Tang, X Ross, RJ Morrison, AR Sanford, LD TI Telemetry for naturalistic sleep recording: Results in inbred and hybrid mice SO SLEEP LA English DT Meeting Abstract C1 Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 712 BP A401 EP A402 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900710 ER PT J AU Xi, X McGinty, D Szymusiak, R AF Xi, X McGinty, D Szymusiak, R TI Acute handling stress induces respiratory depression in rats SO SLEEP LA English DT Meeting Abstract ID POSITIVE AIRWAY PRESSURE; OBSTRUCTIVE SLEEP-APNEA C1 VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 515 BP A296 EP A296 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900514 ER PT J AU Bourget, JL Mathes, DW Nielsen, GP Randolph, MA Tanabe, YN Ferrara, VR Wu, A Sachs, DH Lee, WPA AF Bourget, JL Mathes, DW Nielsen, GP Randolph, MA Tanabe, YN Ferrara, VR Wu, A Sachs, DH Lee, WPA TI Tolerance to musculoskeletal allografts with transient lymphocyte chimerism in miniature swine SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TISSUE LIMB ALLOGRAFTS; RENAL-ALLOGRAFTS; TRANSPLANTATION; SURVIVAL; ANTIGENS; LOCALIZATION; ENDOTHELIUM; CYCLOSPORIN; KIDNEY AB Background Although transplantation of musculoskeletal allografts in humans is technically feasible, the adverse effects of long-term immunosuppression subject the patient to high risks for correcting a non-life-threatening condition. Achieving immunologic tolerance to musculoskeletal allografts, without the need for chronic immunosuppression, could expand the clinical application of limb tissue allografting, Tolerance to musculoskeletal allografts has been accomplished previously in miniature swine in our laboratory. Although stable, mixed chimerism has been suggested as the mechanism underlying long-term tolerance in a rat limb model, the mechanism of this tolerance induction has not been established. This report explores the possible relationship between hematopoietic chimerism and tolerance to musculoskeletal allografts in swine. Methods. Twelve miniature swine underwent vascularized musculoskeletal allograft transplantation from histocompatibility complex (MHC) matched, minor antigen-mismatched donors. Eight animals received a 12-day course of cyclosporine, one of which was excluded due to subtherapeutic levels, Four recipients were not immunosuppressed, Serial biopsies to assess graft viability and flow cytometry to assess chimerism were performed. Donor and third-party skin grafts were placed on recipients with surviving allografts greater than 100 days to validate tolerance. Results, Both groups developed early peripheral chimerism, but this chimerism became undetectable by postoperative day 19 in the cyclosporine group and by day 13 in the control group, Animals receiving cyclosporine developed permanent tolerance to their allografts, whereas those not receiving cyclosporine rejected their allografts in 6-9 weeks. Animals demonstrating tolerance to their bone allografts also demonstrated prolonged donor skin graft survival, Conclusions. Induction of tolerance to musculoskeletal allografts can be achieved in the MHC matched swine. Although hematopoietic chimerism is present in the immediate postoperative period, persistent, long-term chimerism does not seem to be necessary for maintenance of such tolerance. C1 Harvard Univ, Sch Med, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Lee, WPA (reprint author), Harvard Univ, Sch Med, Div Plast Surg, WACC-453,15 Parkman St, Boston, MA 02114 USA. NR 21 TC 31 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2001 VL 71 IS 7 BP 851 EP 856 DI 10.1097/00007890-200104150-00005 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 429DN UT WOS:000168500900005 PM 11349715 ER PT J AU Vasir, B Jonas, JC Steil, GM Hollister-Lock, J Hasenkamp, W Sharma, A Bonner-Weir, S Weir, GC AF Vasir, B Jonas, JC Steil, GM Hollister-Lock, J Hasenkamp, W Sharma, A Bonner-Weir, S Weir, GC TI Gene expression of VEGF and its receptors Flk-1/KDR and Flt-1 in cultured and transplanted rat islets SO TRANSPLANTATION LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1; ORGANIC CATION TRANSPORTER; RENAL MESANGIAL CELLS; UP-REGULATION; PANCREATIC-ISLETS; TYROSINE KINASE; NITRIC-OXIDE; IN-VITRO; KIDNEY AB Background. Vascular endothelial growth factor (VEGF) and its two receptor tyrosine kinases, Flk-1/ KDR and Flt-1, may play an important role in mediating the revascularization of transplanted pancreatic islets. Methods. Using semiquantitative multiplex reverse-transcribed polymerase chain reaction we determined the gene expression of VEGF and its receptors in cultured and transplanted rat islets. Results. After exposure of islet cells to hypoxia in vitro, increases were found in the gene expression of the VEGF120 and VEGF164 isoforms, with simultaneous increases in VE-cadherin, Flk-1/KDR, and Flt-1, In vivo studies consisted of analysis of islet grafts transplanted into both normal and diabetic recipients. Expression of both VEGF120 and VEGF164 in grafts was up-regulated for the first 2-3 days after transplantation, with the response being more prolonged in the diabetic rats. These increases were followed by reduced expression of VEGF on days 5, 7, and 9. Increases in the expression of VE-cadherin in islet grafts in normal and diabetic recipients tended to parallel VEGF expression, with the increases in both probably being caused by hypoxia, The early increases of VE:GF expression were followed by a rise in the expression of VEGF receptors, which probably represents the early stages of angiogenesis. Graft expression of Flk-1/KDR and Flt-1 was enhanced at 3 and 5 days in the normoglycemic recipients, while in the diabetic recipients increases were found later on days 5, 7, and 14. Conclusions. The delayed expression of VEGF receptors in the diabetic recipients could reflect impaired angiogenesis caused by the diabetic milieu; this delay could contribute to the less outcomes of grafts transplanted into a hyperglycemic environment. C1 Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. RI Jonas, Jean-Christophe/C-6766-2011 OI Jonas, Jean-Christophe/0000-0001-9882-5438 FU NIDDK NIH HHS [DK-36836, DK-50657] NR 60 TC 74 Z9 78 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2001 VL 71 IS 7 BP 924 EP 935 DI 10.1097/00007890-200104150-00018 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 429DN UT WOS:000168500900018 PM 11349728 ER PT J AU Cao, C Ren, XP Kharbanda, S Koleske, A Prasad, KVS Kufe, D AF Cao, C Ren, XP Kharbanda, S Koleske, A Prasad, KVS Kufe, D TI The ARG tyrosine kinase interacts with Siva-1 in the apoptotic response to oxidative stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ABL-RELATED GENE; C-ABL; DNA-DAMAGE; PROAPOPTOTIC PROTEIN; CELL; ACTIVATION; BINDING; T(1-12)(Q25-P13); LOCALIZATION; CD27 AB The Abl family of mammalian nonreceptor tyrosine kinases consists of c-Abl and ARG (Abl-related gene). Certain insights are available regarding the involvement c-Abl in the response of cells to stress. ARG, however, has no known function in cell signaling. The present studies demonstrate that ARG associates with the proapoptotic Siva-1 protein. The functional significance of the ARG-Siva-1 interaction is supported by the finding that ARG is activated by oxidative stress and that this response involves ARG-mediated phosphorylation of Siva-1 on Tyr(48). The proapoptotic effects of Siva-1 are accentuated in cells stably expressing ARG and are inhibited in ARG-deficient cells, Moreover, the proapoptotic effects of Siva-1 are abrogated by mutation of the Tyr(48) site. We also show that the apoptotic response to oxidative stress is attenuated in ARG-deficient cells and that this defect is corrected by reconstituting ARG expression. These findings support a model in which the activation of ARG by oxidative stress induces apoptosis by a Siva-1-dependent mechanism. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60612 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42802] NR 29 TC 45 Z9 50 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 11465 EP 11468 DI 10.1074/jbc.C100050200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800006 PM 11278261 ER PT J AU Hong, DH Yue, GH Adamian, M Li, TS AF Hong, DH Yue, GH Adamian, M Li, TS TI Retinitis pigmentosa GTPase regulator (RPGR)-interacting protein is stably associated with the photoreceptor ciliary axoneme and anchors RPGR to the connecting cilium SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-EXCHANGE FACTOR; RETINAL RODS; BASAL BODIES; MYOSIN VIIA; TRANSPORT; MEMBRANE; GENE; MICROTUBULES; LOCALIZATION; HOMOLOGY AB Retinitis pigmentosa (RP) is a blinding retinal disease in which the photoreceptor cells degenerate. Mutations in the gene for retinitis pigmentosa GTPase regulator (RPGR) are a frequent cause of RP. The function of RPGR is not well understood, but it is thought to be a putative guanine nucleotide exchange factor for an unknown G protein. Ablation of the RPGR gene in mice suggested a role in maintaining the polarized distribution of opsin across the cilia. To investigate its function, we used a protein interaction screen to identify candidate proteins that may interact physiologically with RPGR. One such protein, designated RPGR-interacting protein (RPGRIP), is expressed specifically in rod and cone photoreceptors. It consists of an N-terminal region predicted to form coiled coil structures linked to a C-terminal tail that binds RPGR. In vivo, both proteins co-localize in the photoreceptor connecting cilia. RPGRIP is stably associated with the ciliary axoneme independent of RPGR and is resistant to extraction under conditions that partially solubilized other cytoskeletal components. When over-expressed in heterologous cell lines, RPGRIP appears in insoluble punctate and filamentous structures. These data suggest that RPGRIP is a structural component of the ciliary axoneme, and one of its functions is to anchor RPGR within the cilium. RPGRIP is the only protein known to localize specifically in the photoreceptor connecting cilium, As such, it is a candidate gene for human photoreceptor disease. The tissue-specific expression of RPGRIP explains why mutations in the ubiquitously expressed RPGR confer a photoreceptor-specific phenotype. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Li, TS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY10309] NR 35 TC 128 Z9 131 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 12091 EP 12099 DI 10.1074/jbc.M009351200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800089 PM 11104772 ER PT J AU Ballif, BA Shimamura, A Pae, E Blenis, J AF Ballif, BA Shimamura, A Pae, E Blenis, J TI Disruption of 3-phosphoinositide-dependent kinase 1 (PDK1) signaling by the anti-tumorigenic and anti-proliferative agent N-alpha-tosyl-1-phenylalanyl chloromethyl ketone SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RIBOSOMAL S6 KINASE; PHOSPHOINOSITIDE-DEPENDENT KINASE-1; SERINE-PROTEASE INHIBITORS; KAPPA-B ACTIVATION; C-ZETA; MAMMALIAN HOMOLOG; THREONINE KINASE; CELL-SURVIVAL; DUAL ROLE; PHOSPHORYLATION AB The anti-tumorigenic and anti-proliferative effects of N-alpha -tosyl-L-phenylalanyl chloromethyl ketone (TPCK) have been known for more than three decades. Yet little is known about the discrete cellular targets of TPCK controlling these effects. Previous work from our laboratory showed TPCK, like the immunosuppressant rapamycin, to be a potent inhibitor of the 70-kilodalton ribosomal S6 kinase 1 (S6K1), which mediates events involved in cell growth and proliferation. We show here that rapamycin and TPCK display distinct inhibitory mechanisms on S6K1 as a rapamycin-resistant form of S6K1 was TPCK-sensitive, Additionally, we show that TPCK inhibited the activation of the related kinase and proto-oncogene Akt. Upstream regulators of S6K1 and Akt include phosphoinositide S-kinase (PI 3-K) and 3-phosphoinositide-dependent kinase 1 (PDK1). Whereas TPCK had no effect on either mitogen-regulated PI 3-K; activity or total cellular PDK1 activity, TPCK prevented phosphorylation of the PDK1 regulatory sites in S6K1 and Akt. Furthermore, whereas both PDK1 and the mitogen-activated protein kinase (MAPK) are required for full activation of the 90-kilodalton ribosomal S6 kinase (RSK), TPCK inhibited RSK activation without inhibiting MAPK activation. Consistent with the capacity of RSK and Abt to mediate a cell survival signal, in part through phosphorylation of the pro-apoptotic protein BAD, TPCK reduced BAD phosphorylation and led to cell death in interleukin-3-dependent 32D cells. Finally, in agreement with results seen in embryonic stem cells lacking PDK1, protein kinase A activation was not inhibited by TPCK showing TPCK specificity for mitogen-regulated PDK1 signaling. TPCK inhibition of PDK1 signaling thus disables central kinase cascades governing diverse cellular processes including proliferation and survival and provides an explanation for its striking biological effects. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. RP Blenis, J (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NCI NIH HHS [CA4569]; NIGMS NIH HHS [GM51405] NR 73 TC 49 Z9 51 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 12466 EP 12475 DI 10.1074/jbc.M009939200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800137 PM 11278584 ER PT J AU Holmes, LB Harvey, EA Coull, BA Huntington, KB Khoshbin, S Hayes, AM Ryan, LM AF Holmes, LB Harvey, EA Coull, BA Huntington, KB Khoshbin, S Hayes, AM Ryan, LM TI The teratogenicity of anticonvulsant drugs. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FETAL-HYDANTOIN SYNDROME; BIRTH-DEFECTS; ANTIEPILEPTIC DRUGS; GROWTH-RETARDATION; PARENTAL EPILEPSY; NEWBORN-INFANTS; PREGNANCY; MALFORMATIONS; CARBAMAZEPINE; WOMEN AB Background: The frequency of major malformations, growth retardation, and hypoplasia of the midface and fingers, known as anticonvulsant embryopathy, is increased in infants exposed to anticonvulsant drugs in utero. However, whether the abnormalities are caused by the maternal epilepsy itself or by exposure to anticonvulsant drugs is not known. Methods: We screened 128,049 pregnant women at delivery to identify three groups of infants: those exposed to anticonvulsant drugs, those unexposed to anticonvulsant drugs but with a maternal history of seizures, and those unexposed to anticonvulsant drugs with no maternal history of seizures (control group). The infants were examined systematically for the presence of major malformations, signs of hypoplasia of the midface and fingers, microcephaly, and small body size. Results: The combined frequency of anticonvulsant embryopathy was higher in 223 infants exposed to one anticonvulsant drug than in 508 control infants (20.6 percent vs. 8.5 percent; odds ratio, 2.8; 95 percent confidence interval, 1.1 to 9.7). The frequency was also higher in 93 infants exposed to two or more anticonvulsant drugs than in the controls (28.0 percent vs. 8.5 percent; odds ratio, 4.2; 95 percent confidence interval, 1.1 to 5.1). The 98 infants whose mothers had a history of epilepsy but took no anticonvulsant drugs during the pregnancy did not have a higher frequency of those abnormalities than the control infants. Conclusions: A distinctive pattern of physical abnormalities in infants of mothers with epilepsy is associated with the use of anticonvulsant drugs during pregnancy, rather than with epilepsy itself. (N Engl J Med 2001;344:1132-8.) Copyright (C) 2001 Massachusetts Medical Society. C1 Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NINDS NIH HHS [NS 24125] NR 44 TC 346 Z9 355 U1 1 U2 21 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2001 VL 344 IS 15 BP 1132 EP 1138 DI 10.1056/NEJM200104123441504 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 420EC UT WOS:000167990600004 PM 11297704 ER PT J AU Coggins, CH Bazari, H McCluskey, RT Spragg, D Smith, RN AF Coggins, CH Bazari, H McCluskey, RT Spragg, D Smith, RN TI Rapidly progressive renal failure in a 35-year-old woman with systemic lupus erythematosus. Antiphospholipid-antibody syndrome, catastrophic, with renal thrombotic microangiopathy due to systemic lupus erythematosus. Lupus nephritis, mild. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID AUTOANTIBODIES; DIAGNOSIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Coggins, CH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2001 VL 344 IS 15 BP 1152 EP 1158 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 420EC UT WOS:000167990600008 ER PT J AU Lewis, BE Wallis, DE Berkowitz, SD Matthai, WH Fareed, J Walenga, JM Bartholomew, J Sham, R Lerner, RG Zeigler, ZR Rustagi, PK Jang, IK Rifkin, SD Moran, J Hursting, MJ Kelton, JG AF Lewis, BE Wallis, DE Berkowitz, SD Matthai, WH Fareed, J Walenga, JM Bartholomew, J Sham, R Lerner, RG Zeigler, ZR Rustagi, PK Jang, IK Rifkin, SD Moran, J Hursting, MJ Kelton, JG CA ARG-911 Study Investigators TI Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia SO CIRCULATION LA English DT Article DE anticoagulants; inhibitors; heparin; thrombosis; platelets ID RECOMBINANT HIRUDIN; THROMBOSIS; ANTIBODIES; AGE AB Background-Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome caused by heparin. Complications range from thrombocytopenia to thrombocytopenia with thrombosis. We report a prospective, historical-controlled study evaluating the efficacy and safety of argatroban, a direct thrombin inhibitor. as anticoagulant therapy in patients with KIT or HIT with thrombosis syndrome (HITTS). Methods and Results-Patients with HIT (isolated thrombocytopenia, n=160) or HITTS (n=144) received 2 mug . kg(-1) . min(-1) TV argatroban, adjusted to maintain the activated partial thromboplastin time 1.5 to 3.0 times baseline value. Treatment was maintained for 6 days, on average. Clinical outcomes over 37 days were compared with those of 193 historical control subjects with KIT (n=147) or HITTS (n=46). The incidence of the primary efficacy end point, a composite of all-cause death, all-cause amputation, or new thrombosis, was reduced significantly in argatroban-treated patients versus control subjects with HIT (25.6% versus 38.8%, P=0.014). In HITTS, the composite incidence in argatroban-treated patients was 43.8% versus 56.5% in control subjects (P=0.13). Significant between-group differences by time-to-event analysis of the composite end point favored argatroban treatment in HIT (P=0.010) and HITTS (P=0.014). Argatroban therapy, relative to control subjects, also significantly reduced new thrombosis and death caused by thrombosis (P<0.05). Argatroban-treated patients achieved therapeutic activated partial thromboplastin times generally within 4 to 5 hours of starting therapy and, compared with control subjects, had a significantly more rapid rise in platelet counts (P=0.0001). Bleeding events were similar between groups. Conclusions-Argatroban anticoagulation, compared with historical control subjects, improves clinical outcomes in patients who have heparin-induced thrombocytopenia, without increasing bleeding risk. C1 Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Midw Heart Specialists, Downers Grove, IL USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Penn, Philadelphia, PA 19104 USA. Cleveland Clin, Cleveland, OH 44106 USA. Rochester Gen Hosp, Rochester, NY 14621 USA. Westchester Cty Med Ctr, Valhalla, NY 10595 USA. W Penn Hosp, Pittsburgh, PA USA. Univ Alabama, Birmingham, AL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NW Med Specialists, Arlington Heights, IL USA. Texas Biotechnol Corp, Houston, TX USA. McMaster Univ, Hamilton, ON, Canada. RP Lewis, BE (reprint author), Loyola Univ, Med Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 25 TC 409 Z9 419 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 10 PY 2001 VL 103 IS 14 BP 1838 EP 1843 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 422MK UT WOS:000168122300012 PM 11294800 ER PT J AU Wu, FF Takahashi, MP Pegoraro, E Angelini, C Colleselli, P Cannon, SC Hoffman, EP AF Wu, FF Takahashi, MP Pegoraro, E Angelini, C Colleselli, P Cannon, SC Hoffman, EP TI A new mutation in a family with cold-aggravated myotonia disrupts Na+ channel inactivation SO NEUROLOGY LA English DT Article ID HYPERKALEMIC PERIODIC PARALYSIS; GATED SODIUM-CHANNELS; PARAMYOTONIA-CONGENITA; SLOW INACTIVATION; ION CHANNELS; ACTIVATION; POTASSIUM; DISEASE; DEFECT; DNA AB Objective: To identify the molecular and physiologic abnormality in familial myotonia with cold sensitivity, hypertrophy, and no weakness. Background: Sodium channel mutations were previously identified as the cause of several allelic disorders with varying combinations of myotonia and periodic paralysis. A three-generation family with dominant myotonia aggravated by cooling, but no weakness, was screened for mutations in the skeletal muscle sodium channel alpha -subunit gene (SCN4A). Methods: Single-strand conformation polymorphism was used to screen all 24 exons of SCN4A and abnormal conformers were sequenced to confirm the presence of mutations. The functional consequence of a SCN4A mutation was explored by recording sodium currents from human embryonic kidney cells transiently transfected with an expression construct that was mutated to reproduce the genetic defect. Results: A three-generation Italian family with myotonia is presented, in which a novel SCN4A mutation (leucine 266 substituted by valine, L266V) is identified. This change removes only a single methylene group from the 1,836-amino-acid protein, and is present in a region of the protein previously not known to be critical for channel function (domain I transmembrane segment 5). Electrophysiologic studies of the L266V mutation showed defects in fast inactivation, consistent with other disease-causing SCN4A mutations studied to date. Slow inactivation was not impaired. Conclusions: This novel mutation of the sodium channel indicates that a single carbon change in a transmembrane alpha -helix of domain I can alter channel inactivation and cause cold-sensitive myotonia. C1 Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurobiol, Boston, MA USA. Univ Padua, Dept Neurol & Psychiat Sci, Neuromuscular Unit, Padua, Italy. OC Belluno, ULSS Belluno Agordo Cadore 1, Div Pediat, Belluno, Italy. Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. RP Hoffman, EP (reprint author), Childrens Natl Med Ctr, Res Ctr Genet Med, 111 Michigan Ave NW, Washington, DC 20010 USA. OI Angelini, Corrado/0000-0002-9554-8794 FU Telethon [C.54] NR 26 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 10 PY 2001 VL 56 IS 7 BP 878 EP 884 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 419RB UT WOS:000167961500010 PM 11294924 ER PT J AU Kelly, PJ Hedley-Whyte, ET Primavera, J He, J Gonzalez, RG AF Kelly, PJ Hedley-Whyte, ET Primavera, J He, J Gonzalez, RG TI Diffusion MRI in ischemic stroke compared to pathologically verified infarction SO NEUROLOGY LA English DT Article ID PERFUSION-WEIGHTED MRI; MEDICAL LITERATURE; CEREBRAL-ISCHEMIA; DIAGNOSTIC-TESTS; T2-WEIGHTED MRI; USERS GUIDES; INJURY; REPERFUSION; THERAPY; ARTICLE AB Background: Diffusion MRI abnormality correlates with pathology in animal ischemic stroke models. A combined retrospective and prospective analysis of consecutive patients over a 3-year period who had a clinical diagnosis of probable new ischemic stroke, underwent diffusion MRI, and were later studied at autopsy was performed. Methods: Inclusion criteria for the retrospective analysis were 1) symptom onset within 14 days of presentation, 2) diffusion MRI within 28 days of symptom onset, and 3) autopsy within 16 weeks of symptom onset. Patients with suspected further infarcts between;MRI and autopsy were excluded. The locations of all areas of MRI abnormality were identified by a blinded neuroradiologist, and recent infarcts were identified by review of pathologic records and microscopic slides. Results: Eleven patients were identified who fulfilled inclusion criteria, with 25 discrete pathologic infarcts. Diffusion MRI abnormality corresponded to pathologically verified infarction in 23 cases, was present in two locations where no pathologic infarct was identified, and was absent in two locations where an infarct was present at autopsy. In two cases, despite clinical suspicion of acute ischemic stroke, no MRI abnormality or pathologic infarct was found. The sensitivity and specificity of diffusion MRI were 88.5% (95% CI, 69.9% to 97.6%) and 96.6% (95% CI, 91.5% to 99.1%). Accuracy was 95.1% (95% CI? 90.2% to 98%). Three further patients who died during the course of the retrospective analysis were studied prospectively, and are described separately. Conclusions: These findings suggest high accuracy of diffusion MRI for detection of ischemic infarction compared with pathologic examination. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kelly, PJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 802,Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR 13213]; NINDS NIH HHS [NS 34626] NR 25 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 10 PY 2001 VL 56 IS 7 BP 914 EP 920 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 419RB UT WOS:000167961500015 PM 11294929 ER PT J AU Segal, AZ Abernethy, WB Palacios, IF BeLue, R Rordorf, G AF Segal, AZ Abernethy, WB Palacios, IF BeLue, R Rordorf, G TI Stroke as a complication of cardiac catheterization: Risk factors and clinical features SO NEUROLOGY LA English DT Article ID REGISTRY; EVENTS AB The authors aimed to delineate the risk factors and radiologic pattern of stroke complicating cardiac catheterization. Twenty-two cases were matched with three control subjects. Stroke was significantly associated with severity of coronary artery disease and length of fluoroscopy time (OR 1.96 and 1.65). The use of MRI with diffusion weighting allowed the identification of multiple asymptomatic lesions and a subset of lacunar-type infarcts (23%), which most likely occurred on an atheroembolic basis. C1 Cornell Univ, Med Ctr, Dept Neurol, New York, NY 10021 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02115 USA. RP Segal, AZ (reprint author), Cornell Univ, Med Ctr, Dept Neurol, 525 E 68th St,Room F610, New York, NY 10021 USA. NR 10 TC 56 Z9 57 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 10 PY 2001 VL 56 IS 7 BP 975 EP 977 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 419RB UT WOS:000167961500027 PM 11294941 ER PT J AU Martelli, F Hamilton, T Silver, DP Sharpless, NE Bardeesy, N Rokas, M DePinho, RA Livingston, DM Grossman, SR AF Martelli, F Hamilton, T Silver, DP Sharpless, NE Bardeesy, N Rokas, M DePinho, RA Livingston, DM Grossman, SR TI p19ARF targets certain E2F species for degradation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETINOBLASTOMA FAMILY PROTEINS; UBIQUITIN-PROTEASOME PATHWAY; TRANSCRIPTION FACTOR E2F-1; P19(ARF) TUMOR-SUPPRESSOR; PACKAGING CELL-LINE; STABILIZES P53; GENE-PRODUCT; IN-VITRO; S-PHASE; MDM2 AB p19ARF suppresses the growth of cells lacking p53 through an unknown mechanism. p19ARF was found to complex with transcription factors E2F1, -2, and -3. Levels of endogenous or ectopically expressed E2F1, -2, and -3, but not E2F6, were reduced after synthesis of p19ARF, through a mechanism involving increased turnover. p19ARF-induced degradation of E2F1 depended on a functional proteasome, and E2F1 was relocalized to nucleoli when coexpressed with p19ARF. Consistent with reduced levels of E2F1 and E2F3, the proliferation of cells defective for p53 function was suppressed by p19ARF, and the effect was partially reversed by ectopic overexpression of E2F1. These results suggest a broader role for p19ARF as a tumor suppressor, in which targeting of certain E2F species may cooperate with stimulation of the p53 pathway to counteract oncogenic growth signals. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,SM870, Boston, MA 02115 USA. OI Martelli, Fabio/0000-0002-8624-7738 FU NCI NIH HHS [P01 CA050661, P01 CA50661-12] NR 49 TC 135 Z9 138 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2001 VL 98 IS 8 BP 4455 EP 4460 DI 10.1073/pnas.081061398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421HV UT WOS:000168059700037 PM 11274364 ER PT J AU Pluen, A Boucher, Y Ramanujan, S McKee, TD Gohongi, T di Tomaso, E Brown, EB Izumi, Y Campbell, RB Berk, DA Jain, RK AF Pluen, A Boucher, Y Ramanujan, S McKee, TD Gohongi, T di Tomaso, E Brown, EB Izumi, Y Campbell, RB Berk, DA Jain, RK TI Role of tumor-host interactions in interstitial diffusion of macromolecules: Cranial vs. subcutaneous tumors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXTRACELLULAR-MATRIX; HYALURONIC-ACID; VOLUME FRACTION; SKIN FRAGILITY; DECORIN; CARCINOMA; COLLAGEN; TISSUE; TORTUOSITY; EXPRESSION AB The large size of many novel therapeutics impairs their transport through the tumor extracellular matrix and thus limits their therapeutic effectiveness. We propose that extracellular matrix composition, structure, and distribution determine the transport properties in tumors. Furthermore, because the characteristics of the extracellular matrix largely depend on the tumor-host interactions, we postulate that diffusion of macromolecules will vary with tumor type as well as anatomical location. Diffusion coefficients of macromolecules and liposomes in tumors growing in cranial windows (CWs) and dorsal chambers (DCs) were measured by fluorescence recovery after photobleaching. For the same tumor types, diffusion of large molecules was significantly faster in CW than in DC tumors. The greater diffusional hindrance in DC tumors was correlated with higher levels of collagen type I and its organization into fibrils. For molecules with diameters comparable to the interfibrillar space the diffusion was 5- to 10-fold slower in DC than in CW tumors. The slower diffusion in DC tumors was associated with a higher density of host stromal cells that synthesize and organize collagen type I. Our results point to the necessity of developing site-specific drug carriers to improve the delivery of molecular medicine to solid tumors. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Div Bioengn & Environm Hlth, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Berk, David/A-4863-2012; Pluen, Alain/F-5300-2015; OI Berk, David/0000-0002-3855-6886; Pluen, Alain/0000-0002-5953-8011; McKee, Trevor/0000-0002-2195-6146 FU NCI NIH HHS [F32 CA083248, F32-CA83248, P01 CA080124, P01-CA-80124, R35-CA56591, T32 CA073479, T32-CA73479]; NIGMS NIH HHS [5 T32 GM08334, T32 GM008334] NR 42 TC 290 Z9 294 U1 0 U2 28 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2001 VL 98 IS 8 BP 4628 EP 4633 DI 10.1073/pnas.081626898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421HV UT WOS:000168059700066 PM 11274375 ER PT J AU Hadjikhani, N del Rio, MS Wu, O Schwartz, D Bakker, D Fischl, B Kwong, KK Cutrer, FM Rosen, BR Tootell, RBH Sorensen, AG Moskowitz, MA AF Hadjikhani, N del Rio, MS Wu, O Schwartz, D Bakker, D Fischl, B Kwong, KK Cutrer, FM Rosen, BR Tootell, RBH Sorensen, AG Moskowitz, MA TI Mechanisms of migraine aura revealed by functional MRI in human visual cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CEREBRAL BLOOD-FLOW; CORTICAL SPREADING DEPRESSION; BASILAR ARTERY MIGRAINE; SURFACE-BASED ANALYSIS; HMPAO BRAIN SPECT; CLASSIC MIGRAINE; OXYGEN-CONSUMPTION; HYPOPERFUSION; HEADACHE; OLIGEMIA AB Cortical spreading depression (CSD) has been suggested to underlie migraine Visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 +/- 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the Visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Neurovasc Lab, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Nucl Magnet Resonance Ctr, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM moskowitz@helix.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008; Moskowitz, Michael/D-9916-2011 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU NCRR NIH HHS [P41 RR 14075]; NEI NIH HHS [EY 07980]; NINDS NIH HHS [5 PO1 NS 35611, K08-NS01803A] NR 53 TC 658 Z9 675 U1 6 U2 37 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2001 VL 98 IS 8 BP 4687 EP 4692 DI 10.1073/pnas.071582498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421HV UT WOS:000168059700076 PM 11287655 ER PT J AU Hakak, Y Walker, JR Li, C Wong, WH Davis, KL Buxbaum, JD Haroutunian, V Fienberg, AA AF Hakak, Y Walker, JR Li, C Wong, WH Davis, KL Buxbaum, JD Haroutunian, V Fienberg, AA TI Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PREFRONTAL CORTEX; OLIGODENDROCYTE DEVELOPMENT; OLIGONUCLEOTIDE ARRAYS; TRANSGENIC MICE; PROTEIN GAP-43; DENSITY; RECEPTOR; OVEREXPRESSION; NEUROPATHOLOGY; GLYCOPROTEIN AB Neuropathological and brain imaging studies suggest that schizophrenia may result from neurodevelopmental defects. Cytoarchitectural studies indicate cellular abnormalities suggestive of a disruption in neuronal connectivity in schizophrenia, particularly in the dorsolateral prefrontal cortex. Yet, the molecular mechanisms underlying these findings remain unclear. To identify molecular substrates associated with schizophrenia, DNA microarray analysis was used to assay gene expression levels in postmortem dorsolateral prefrontal cortex of schizophrenic and control patients. Genes determined to have altered expression levels in schizophrenics relative to controls are involved in a number of biological processes, including synaptic plasticity, neuronal development, neurotransmission, and signal transduction. Most notable was the differential expression of myelination-related genes suggesting a disruption in oligodendrocyte function in schizophrenia. C1 Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10021 USA. Bronx Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY 10468 USA. RP Fienberg, AA (reprint author), Novartis Res Fdn, Genom Inst, 3115 Merryfield Row, San Diego, CA 92121 USA. OI Buxbaum, Joseph/0000-0001-8898-8313 FU NIMH NIH HHS [MH45212] NR 40 TC 817 Z9 839 U1 1 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2001 VL 98 IS 8 BP 4746 EP 4751 DI 10.1073/pnas.081071198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421HV UT WOS:000168059700086 PM 11296301 ER PT J AU Levine, GN Ali, MN Schafer, AI AF Levine, GN Ali, MN Schafer, AI TI Antithrombotic therapy in patients with acute coronary syndromes SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA-PECTORIS; MOLECULAR-WEIGHT HEPARIN; PRACTICE GUIDELINES COMMITTEE; TISSUE-PLASMINOGEN-ACTIVATOR; DIRECT THROMBIN-INHIBITOR; CLINICAL-TRIALS SESSIONS; PLACEBO-CONTROLLED TRIAL; ASSOCIATION TASK-FORCE; UNFRACTIONATED HEPARIN AB The potential armamentarium of agents used in the treatment of acute coronary syndromes continues to expand, including such well-tested agents as aspirin, unfractionated heparin, and earlier-generation fibrinolytic agents, and newer agents such as low-molecular-weight heparins, direct thrombin inhibitors, thienopyridines, platelet glycoprotein IIb/IIIa receptor inhibitors, and bolus-administration fibrinolytic agents. Older and newer antithrombotic agents have undergone and continue to undergo intensive clinical investigation in patients with the clinical spectrum of acute coronary syndromes, which includes unstable angina, non-Q-wave (non-ST-segment elevation) myocardial infarction, and ST-segment elevation myocardial infarction. These studies, often conducted on an international scope and involving thousands of patients, provide data allowing practitioners to optimize the care of patients with acute coronary syndromes. In this article, studies of these established and newer agents in the treatment of patients with acute coronary syndromes are reviewed critically and summarized. Recommendations regarding use of antithrombotic agents inpatients with acute coronary syndromes are then given. C1 Houston VA Med Ctr 111B, Sect Cardiol 3C330, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. RP Levine, GN (reprint author), Houston VA Med Ctr 111B, Sect Cardiol 3C330, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI bashzar, salman/R-5748-2016 NR 99 TC 19 Z9 19 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 9 PY 2001 VL 161 IS 7 BP 937 EP 948 DI 10.1001/archinte.161.7.937 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 419HY UT WOS:000167944300005 PM 11295956 ER PT J AU Lloyd-Jones, DM O'Donnell, CJ D'Agostino, RB Massaro, J Silbershatz, H Wilson, PWF AF Lloyd-Jones, DM O'Donnell, CJ D'Agostino, RB Massaro, J Silbershatz, H Wilson, PWF TI Applicability of cholesterol-lowering primary prevention trials to a general population - The Framingham heart study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DENSITY LIPOPROTEIN CHOLESTEROL; COST-EFFECTIVENESS; RISK-FACTORS; DISEASE; MEN; PREVALENCE; ADULTS AB Background: Four large trials have shown cholesterol-reduction therapy to be effective for primary prevention of coronary heart disease (CHD). Methods: To determine the generalizability of these trials to a community-based sample, we compared the total cholesterol and high-density lipoprotein cholesterol (HDL-C) distributions of patients in the 4 trials with. those of Framingham Heart Study subjects. Lipid profiles that have not been studied were identified. Twelve-year rates of incident CHD were compared between subjects who met eligibility criteria and those who did not. Results: The Framingham sample included 2498 men and 2870 women aged 30 to 74 years. Among Framingham men, 23.4% to 42.0% met eligibility criteria for each of the 4 trials based on their lipid levels; 60.2% met eligibility criteria for at least 1 trial. For the 1 trial that included women, 20.2% of Framingham women met eligibility criteria. In general, subjects with desirable total cholesterol levels and lower HDL-C levels and subjects with average total cholesterol levels and average to higher HDL-C levels have not been included in these trials. Among subjects who developed incident CHD during follow-up, 25.1% of men and 66.2% of women would not have been eligible for any trial. Most ineligible subjects who developed CHD had isolated hypertriglyceridemia (>2.25 mmol/L [>200 mg/dL]). Conclusions: In our sample, 40% of men and 80% of women had lipid profiles that have not been studied in large trials to date. We observed a large number of CHD events in "ineligible" subjects in whom hypertriglyceridemia was common. Further studies are needed to define the role of lipid-lowering therapy vs other strategies for primary prevention in the general population. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Dept Stat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Wilson, PWF (reprint author), Framingham Heart Dis Epidemiol Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-38038] NR 27 TC 40 Z9 40 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 9 PY 2001 VL 161 IS 7 BP 949 EP 954 DI 10.1001/archinte.161.7.949 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 419HY UT WOS:000167944300006 PM 11295957 ER PT J AU Smoller, JW Rosenbaum, JF Biederman, J Susswein, LS Kennedy, J Kagan, J Snidman, N Laird, N Tsuang, MT Faraone, SV Schwarz, A Slaugenhaupt, SA AF Smoller, JW Rosenbaum, JF Biederman, J Susswein, LS Kennedy, J Kagan, J Snidman, N Laird, N Tsuang, MT Faraone, SV Schwarz, A Slaugenhaupt, SA TI Genetic association analysis of behavioral inhibition using candidate loci from mouse models SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 1999 CL ACAPULCO, MEXICO SP Amer Coll Neuropsychopharmacol DE genetic; behavioral inhibition; anxiety; candidate genes; mouse; association study ID ADENOSINE A(2A) RECEPTOR; FAMILY-BASED TESTS; GLUTAMIC-ACID DECARBOXYLASE; QUANTITATIVE TRAIT LOCI; PANIC DISORDER; SOCIAL PHOBIA; LINKAGE DISEQUILIBRIUM; ANXIETY DISORDERS; MAJOR DEPRESSION; MICE DEFICIENT AB Genes influence the development of anxiety disorders, but the specific loci involved are not known. Genetic association studies of anxiety disorders are complicated by the complexity of the phenotypes and the difficulty in identifying appropriate candidate loci, S Ve have begun to examine the genetics of behavioral inhibition to the unfamiliar (BI), a heritable temperamental predisposition that is a developmental and familial risk factor for panic and phobic disorders. Specific loci associated with homologous phenotypes in mouse models provide compelling candidate genes for human BI. We conducted family-based association analyses of BI using four genes derived from genetic studies of mouse models with features of behavioral inhibition. The sample included families of 72 children classified as inhibited by structured behavioral assessments. We observed modest evidence of association (P=0.05) between BI and the glutamic acid decarboxylase gene (65 kDA isoform), which encodes an enzyme involved in GABA synthesis. No significant evidence of association was observed for the genes encoding the adenosine A(1A) receptor, the adenosine A(2A) receptor, or preproenkephalin, This study illustrates the potential utility of using candidate genes derived from mouse models to dissect the genetic basis of BI, a possible intermediate phenotype for panic and phobic disorders, (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA USA. Harvard Univ, Dept Psychol & Social Relat, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC-815, Boston, MA 02114 USA. EM jordan_smoller@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R25MH60485, T32MH17119] NR 93 TC 48 Z9 48 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD APR 8 PY 2001 VL 105 IS 3 BP 226 EP 235 DI 10.1002/ajmg.1328 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 429AT UT WOS:000168494400003 PM 11353440 ER PT J AU Lu, Q Sun, EE Klein, RS Flanagan, JG AF Lu, Q Sun, EE Klein, RS Flanagan, JG TI Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction SO CELL LA English DT Article ID RECEPTOR TYROSINE KINASES; DOMAIN-CONTAINING PROTEIN; CENTRAL-NERVOUS-SYSTEM; CELL-MIGRATION; CARDIOVASCULAR DEVELOPMENT; CAENORHABDITIS-ELEGANS; CEREBELLAR DEVELOPMENT; TRANSMEMBRANE LIGANDS; CYTOPLASMIC DOMAIN; AXON GUIDANCE AB Transmembrane B ephrins and their Eph receptors signal bidirectionally. However, neither the cell biological effects nor signal transduction mechanisms of the reverse signal are well understood. We describe a cytoplasmic protein, PDZ-RGS3, which binds B ephrins through a PDZ domain, and has a regulator of heterotrimeric G protein signaling (RGS) domain. PDZ-RGS3 can mediate signaling from the ephrin-B cytoplasmic tail. SDF-1, a chemokine with a G protein-coupled receptor, or BDNF, act as chemoattractants for cerebellar granule cells, with SDF-1 action being selectively inhibited by soluble EphB receptor. This study reveals a pathway that links reverse signaling to cellular guidance, uncovers a novel mode of control for G proteins, and demonstrates a mechanism for selective regulation of responsiveness to neuronal guidance cues. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. RP Flanagan, JG (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [HD29417]; NINDS NIH HHS [NS40043] NR 63 TC 285 Z9 288 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 6 PY 2001 VL 105 IS 1 BP 69 EP 79 DI 10.1016/S0092-8674(01)00297-5 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 421KJ UT WOS:000168063300008 PM 11301003 ER PT J AU Cantor, SB Bell, DW Ganesan, S Kass, EM Drapkin, R Grossman, S Wahrer, DCR Sgroi, DC Lane, WS Haber, DA Livingston, DM AF Cantor, SB Bell, DW Ganesan, S Kass, EM Drapkin, R Grossman, S Wahrer, DCR Sgroi, DC Lane, WS Haber, DA Livingston, DM TI BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function SO CELL LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; RNA-POLYMERASE-II; DOUBLE-STRAND BREAKS; MAMMALIAN-CELLS; TRANSCRIPTIONAL ACTIVATION; BASAL TRANSCRIPTION; DAMAGE RESPONSE; MEIOTIC CELLS; YEAST RAD3; TFIIH AB BRCA1 interacts in vivo with a novel protein, BACH1, a member of the DEAH helicase family. BACH1 binds directly to the BRCT repeats of BRCA1.A BACH1 derivative, bearing a mutation in a residue that was essential for catalytic function in other helicases, interfered with normal double-strand break repair in a manner that was dependent on its BRCA1 binding function. Thus, BACH1/BRCA1 complex formation contributes to a key BRCA1 activity. In addition, germline BACH1 mutations affecting the helicase domain were detected in two early-onset breast cancer patients and not in 200 matched controls. Thus, it is conceivable that, like BRCA1, BACH1 is a target of germline cancer-inducing mutations. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc Risk Anal, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Harvard Univ, Microchem & Proteom Anal Facil, Cambridge, MA 02138 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU NCI NIH HHS [P50 CA89393]; NHLBI NIH HHS [T32 HL07627-16] NR 58 TC 400 Z9 414 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 6 PY 2001 VL 105 IS 1 BP 149 EP 160 DI 10.1016/S0092-8674(01)00304-X PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 421KJ UT WOS:000168063300015 PM 11301010 ER PT J AU Cheng, LL Wu, CL Smith, MR Gonzalez, RG AF Cheng, LL Wu, CL Smith, MR Gonzalez, RG TI Non-destructive quantitation of spermine in human prostate tissue samples using HRMAS H-1 NMR spectroscopy at 9.4 T SO FEBS LETTERS LA English DT Article DE human prostate; spermine; proton nuclear magnetic resonance spectroscopy; high resolution magic angle spinning; intact tissue specimen; citrate ID MAGNETIC-RESONANCE SPECTROSCOPY; CANCER; RESOLUTION; BENIGN; HYPERPLASIA; INHIBITOR; SPECTRA; CITRATE; GROWTH; CELLS AB We present the results of a study of human prostate specimens evaluated by high resolution magic angle spinning H-1 nuclear magnetic resonance (NMR) spectroscopy at 400 MHz (9.4 T) and by quantitative histopathology, We demonstrate that NMR and pathology data can be obtained from the same intact specimens, and report for the first time a linear correlation between the NMR measured concentration of spermine, a proposed endogenous inhibitor to prostate cancer growth, and the volume percentage of normal prostatic epithelial cells as quantified by histopathology, Our results show that NMR may serve as a critical tool for the investigation of the inhibitory mechanism of spermine in human subjects. (C) 2001 Published by Elsevier Science B,V, on behalf of the Federation of European Biochemical Societies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Cheng, LL (reprint author), Pathol Res CNY 7, 149 13th St, Charlestown, MA 02129 USA. EM cheng@nmr.mgh.harvard.edu FU NCI NIH HHS [CA77727, CA80901] NR 16 TC 109 Z9 111 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 6 PY 2001 VL 494 IS 1-2 BP 112 EP 116 DI 10.1016/S0014-5793(01)02329-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 421LG UT WOS:000168065400023 PM 11297745 ER PT J AU Jiang, YP Ballou, LM Lin, RZ AF Jiang, YP Ballou, LM Lin, RZ TI Rapamycin-insensitive regulation of 4E-BP1 in regenerating rat liver SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P70 S6 KINASE; PROTEIN PHOSPHATASE 2A; MESSENGER-RNA TRANSLATION; MAMMALIAN TARGET; PHAS-I; PHOSPHORYLATION SITES; 3-KINASE INHIBITORS; INITIATION-FACTORS; SIGNALING PATHWAY; TOR PROTEINS AB In cultured cells, growth factor-induced phosphorylation of two translation modulators, p70 S6 kinase and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), is blocked by nanomolar concentrations of the immunosuppressant rapamycin. Rapamycin also attenuates liver regeneration after partial hepatectomy, but it is not known if this growth-suppressive effect is due to dephosphorylation of p70 S6 kinase and/or 4E-BP1. We found that partial hepatectomy induced a transient increase in liver p70 S6 kinase activity and 4E-8P1 phosphorylation as compared with sham-operated rats. The amount of p70 S6 kinase protein in regenerating liver did not increase, but active kinase from partially hepatectomized animals was highly phosphorylated. Phosphorylated 4E-BP1 from regenerating liver was unable to form an inhibitory complex with initiation factor 4E. Rapamycin blocked the activation of p70 S6 kinase in response to partial hepatectomy in a dose-dependent manner, but 4E-BP1 phosphorylation was not inhibited. By contrast, functional phosphorylation of 4E-BP1 induced by injection of cycloheximide or growth factors was partially reversed by the drug. The mammalian target of rapamycin (mTOR) has been proposed to directly phosphorylate 4E-BP1. Western blot analysis using phospho-specific antibodies showed that phosphorylation of Thr-36/45 and Ser-64 increased in response to partial hepatectomy in a rapamycin-resistant manner. Thus, rapamycin inhibits p70 S6 kinase activation and liver regeneration, but not functional phosphorylation of 4E-BP1, in response to partial hepatectomy. These results indicate that the effect of rapamycin on 4E-BP1 function in vivo can be significantly different from its effect in cultured cells. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp, Res Serv, San Antonio, TX 78229 USA. RP Lin, RZ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Mail Code 7764,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Lin, Richard/J-1754-2014 OI Lin, Richard/0000-0002-3473-7276 NR 63 TC 56 Z9 56 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2001 VL 276 IS 14 BP 10943 EP 10951 DI 10.1074/jbc.M007758200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 420AC UT WOS:000167980900052 PM 11278364 ER PT J AU Zaika, A Irwin, M Sansome, C Moll, UM AF Zaika, A Irwin, M Sansome, C Moll, UM TI Oncogenes induce and activate endogenous p73 protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILD-TYPE P73; P53 HOMOLOG P73; KINASE C-ABL; P53-RELATED PROTEIN; CELL-LINES; APOPTOTIC RESPONSE; P53-HOMOLOG P73; ADENOVIRUS E1A; DNA-DAMAGE; GENE AB The identification of upstream pathways that signal to TP73 is crucial for understanding the biological role of this gene. Since some evidence suggests that TP73 might play a role in tumorigenesis, we asked whether oncogenes can induce and activate endogenous TP73. Here, we show that endogenous p73 alpha and beta proteins are up-regulated in p53-deficient tumor cells in response to overexpressed E2F1, c-Myc, and Elk E2F1, c-Myc, and E1A-mediated p73 up-regulation leads to activation of the p73 transcription function, as shown by p73-responsive reporter activity and by induction of known endogenous p73 target gene products such as p21 and HDM2. Importantly, E2F1-, c-Myc-, and E1A-mediated activation of endogenous p73 induces apoptosis in SaOs-2 cells. Conversely, inactivation of p73 by a dominant negative p73 inhibitor (p73DD), but not by a mutant p73DD, inhibits oncogene-induced apoptosis. These data show that oncogenes can signal to TP73 in vivo. Moreover, in the absence of p53, oncogenes may enlist p73 to induce apoptosis in tumor cells. C1 SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Moll, UM (reprint author), SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA. NR 59 TC 115 Z9 116 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2001 VL 276 IS 14 BP 11310 EP 11316 DI 10.1074/jbc.M005737200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 420AC UT WOS:000167980900099 PM 11115495 ER PT J AU Keefe, AD Szostak, JW AF Keefe, AD Szostak, JW TI Functional proteins from a random-sequence library SO NATURE LA English DT Article ID IN-VITRO SELECTION; RNA; BINDING; FUSIONS AB Functional primordial proteins presumably originated from random sequences, but it is not known how frequently functional, or even folded, proteins occur in collections of random sequences. Here we have used in vitro selection of messenger RNA displayed proteins, in which each protein is covalently linked through its carboxy terminus to the 3' end of its encoding mRNA(1), to sample a large number of distinct random sequences. Starting from a library of 6 x 10(12) proteins each containing 80 contiguous random amino acids, we selected functional proteins by enriching for those that bind to ATP. This selection yielded four new ATP-binding proteins that appear to be unrelated to each other or to anything found in the current databases of biological proteins. The frequency of occurrence of functional proteins in random-sequence libraries appears to be similar to that observed for equivalent RNA libraries(2,3). C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RI lu, zhenghui/N-2903-2014 FU Howard Hughes Medical Institute NR 15 TC 312 Z9 319 U1 1 U2 37 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 5 PY 2001 VL 410 IS 6829 BP 715 EP 718 DI 10.1038/35070613 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 418DJ UT WOS:000167875400053 PM 11287961 ER PT J AU Joensuu, H Roberts, PJ Sarlomo-Rikala, M Andersson, LC Tervahartiala, P Tuveson, D Silberman, SL Capdeville, R Dimitrijevic, S Druker, B Demetri, GD AF Joensuu, H Roberts, PJ Sarlomo-Rikala, M Andersson, LC Tervahartiala, P Tuveson, D Silberman, SL Capdeville, R Dimitrijevic, S Druker, B Demetri, GD TI Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID C-KIT; MUTATIONS; LEIOMYOSARCOMAS C1 Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00029 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Radiol, FIN-00029 Helsinki, Finland. Univ Turku, Cent Hosp, Dept Surg, FIN-20520 Turku, Finland. Univ Helsinki, Haartman Inst, Dept Pathol, Helsinki, Finland. MIT, Dept Biol, Cambridge, MA USA. MIT, Howard Hughes Med Inst, Cambridge, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Novartis Oncol, E Hanover, NJ USA. Novartis Oncol, Basel, Switzerland. Oregon Hlth Sci Univ, Dept Med Oncol, Portland, OR 97201 USA. RP Joensuu, H (reprint author), Univ Helsinki, Cent Hosp, Dept Oncol, Haartmaninkatu 4,POB 180, FIN-00029 Helsinki, Finland. NR 10 TC 1252 Z9 1341 U1 1 U2 21 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 5 PY 2001 VL 344 IS 14 BP 1052 EP 1056 DI 10.1056/NEJM200104053441404 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 417XH UT WOS:000167860400004 PM 11287975 ER PT J AU Makhlouf, AA Namboodiri, AMS McDermott, PJ AF Makhlouf, AA Namboodiri, AMS McDermott, PJ TI Transcriptional regulation of the rat eIF4E gene in cardiac muscle cells: the role of specific elements in the promoter region SO GENE LA English DT Article DE translation; protein synthesis; initiation factors; hypertrophy ID EUKARYOTIC TRANSLATION INITIATION; MESSENGER-RNA; FACTOR EIF-4E; C-MYC; PROTEIN-SYNTHESIS; EXPRESSION; GROWTH; OVEREXPRESSION; PROGRESSION; EIF-2-ALPHA AB Eukaryotic initiation factor 4E (eIF4E) binds to the 7-methylguanosine cap of mRNA and facilitates binding of mRNA to the 40 S ribosome, a rate-limiting step in translation initiation. The expression of eIF4E mRNA and protein increases during growth of cardiac muscle cells (cardiocytes) in vitro. To examine transcriptional regulation of the rat eIF4E gene, 2.1 kB of the rat eIF4E promoter region was cloned and the contribution of specific elements in regulating transcription was determined in primary cultures of rat cardiocytes and in a murine C2C12 myoblast cell line. Sequence analysis of the rat eIF4E promoter revealed 80% sequence similarity with human eIF4E. A putative distal E-box was found at -230 bp and a proximal E-box was located at -77 bp upstream of the transcription start site. Consensus AP-1 motifs were found at -839 and -901 bp and designated as the proximal AP-1 site and distal AP-1 site, respectively. Transfection of reporter gene constructs into cardiocytes showed that deletion of the region between -633 and -318 bp produced a 3-fold increase in basal transcription as compared to the 2.1 kB eIF4E promoter construct. Further deletion of the distal E-box region had no effect on transcription as compared with ;the 2.1 kB promoter, but deletion of both E-boxes eliminated transcriptional activity. Similar results were obtained in C2C12 myoblasts. To further investigate transcriptional regulation, point mutations were made in the 2.1 kB eIF4E promoter. Mutation of either the distal or proximal E-box had minimal effects on activity in either cell type, but mutation of the distal AP-1 site significantly reduced eIF4E promoter activity by 66 +/- 4% in cardiocytes. In C2C12 myoblasts, mutating the distal AP-1 site reduced activity by 30 +/- 4%. We conclude that both E-boxes are required for maximal basal activity of the eIF4E promoter, and that the distal AP-1 motif may activate transcription. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP McDermott, PJ (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. NR 33 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 4 PY 2001 VL 267 IS 1 BP 1 EP 12 DI 10.1016/S0378-1119(01)00399-7 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 424FU UT WOS:000168222300001 PM 11311550 ER PT J AU Schwartz, GG Olsson, AG Ezekowitz, MD Ganz, P Oliver, MF Waters, D Zeiher, A Chaitman, BR Leslie, S Stern, T AF Schwartz, GG Olsson, AG Ezekowitz, MD Ganz, P Oliver, MF Waters, D Zeiher, A Chaitman, BR Leslie, S Stern, T CA Myocardial Ischemia Reduction Agg TI Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes - The MIRACL study: A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMPROVES ENDOTHELIAL FUNCTION; CHOLESTEROL REDUCTION; MYOCARDIAL-INFARCTION; BASE-LINE; ATHEROSCLEROSIS; HYPERLIPIDEMIA; SIMVASTATIN; PRAVASTATIN; INHIBITION AB Context Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. Objective To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. Design and Setting A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. Patients A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. Interventions Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. Main Outcome Measures Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. Results A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P = .048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P = .02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12 vs 24 events; P = .045). In the atorvastatin group, mean low-density lipoprotein cholesterol level declined from 124 mg/dL (3.2 mmol/L) to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P < .001). Conclusion For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization. C1 Denver VA Med Ctr, Cardiol Sect 111B, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Linkoping Univ, Fac Hlth Sci, Linkoping, Sweden. Hahnemann Univ, Philadelphia, PA USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Frankfurt, Dept Cardiol, D-6000 Frankfurt, Germany. St Louis Univ, Sch Med, Div Cardiol, St Louis, MO USA. Pfizer Pharmaceut Res, New York, NY USA. Pfizer Pharmaceut Res, Ann Arbor, MI USA. RP Schwartz, GG (reprint author), Denver VA Med Ctr, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. NR 19 TC 1510 Z9 1638 U1 1 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 4 PY 2001 VL 285 IS 13 BP 1711 EP 1718 DI 10.1001/jama.285.13.1711 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 415FR UT WOS:000167710600024 PM 11277825 ER PT J AU Hodgson, DC Fuchs, CS Ayanian, JZ AF Hodgson, DC Fuchs, CS Ayanian, JZ TI Impact of patient and provider characteristics on the treatment and outcomes of colorectal cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID LARGE-BOWEL-CANCER; FEE-FOR-SERVICE; HEALTH MAINTENANCE ORGANIZATIONS; SURGEON-RELATED FACTORS; COLON-CANCER; RECTAL-CANCER; UNITED-STATES; ADJUVANT THERAPY; PROGNOSTIC FACTORS; MEDICARE BENEFICIARIES AB While the management and prognosis of colorectal cancer are largely dependent on clinical features such as tumor stage, there is considerable variation in treatment and outcome not explained by traditional prognostic factors. To guide efforts by researchers and health-care providers to improve quality of care, we review studies of variation in treatment and outcome by patient and provider characteristics. Surgeon expertise and case volume are associated with improved tumor control, although surgeon and hospital factors are not associated consistently with perioperative mortality or long-term survival, Some studies indicate that patients are less likely to undergo permanent colostomy if they are treated by high-volume surgeons and hospitals. Differences in treatment and outcome of patients managed by health maintenance organizations or fee-for-service providers have not generally been found. Older patients are less likely to receive adjuvant therapy after surgery, even after adjustment for comorbid illness. In the United States, black patients with colorectal cancer receive less aggressive therapy and are more likely to die of this disease than white patients, but cancer-specific survival differences are reduced or eliminated when black patients receive comparable treatment. Patients of low socioeconomic status (SES) have worse survival than those of higher SES, although the reasons for this discrepancy are not well understood. Variations in treatment may arise from inadequate physician knowledge of practice guidelines, treatment decisions based on unmeasured clinical factors, or patient preferences. To improve quality of care for colorectal cancer, a better understanding of mechanisms underlying associations between patient and provider characteristics and outcomes is required. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Univ Toronto, Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON, Canada. Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU AHRQ HHS [R01HS09869]; NCI NIH HHS [CA66385] NR 85 TC 138 Z9 141 U1 0 U2 10 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 4 PY 2001 VL 93 IS 7 BP 501 EP 515 DI 10.1093/jnci/93.7.501 PG 15 WC Oncology SC Oncology GA 416UT UT WOS:000167799100011 PM 11287444 ER PT J AU Bill, CA Taghian, DG Duran, WA Nickoloff, JA AF Bill, CA Taghian, DG Duran, WA Nickoloff, JA TI Repair bias of large loop mismatches during recombination in mammalian cells depends on loop length and structure SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE homologous recombination; heteroduplex DNA; palindromes; MSH2; genome stability; DNA polymerase slippage ID NUCLEOTIDE-EXCISION-REPAIR; NONPOLYPOSIS COLON-CANCER; THYMINE-DNA GLYCOSYLASE; SINGLE-STRANDED LOOPS; HAMSTER OVARY CELLS; SHORT PATCH REPAIR; SACCHAROMYCES-CEREVISIAE; HETERODUPLEX DNA; MICROSATELLITE INSTABILITY; ESCHERICHIA-COLI AB Repair of loop mismatches was investigated in wild-type and mismatch binding-defective Chinese hamster ovary (CHO) cells. Loop mismatches were formed in vivo during extrachromosomal recombination between heteroallelic plasmid substrates. Recombination was expected to occur primarily by single-strand annealing (SSA), yielding 12- or 26-base nonpalindromic loop mismatches, and 12-, 26-, or 40-base palindromic loop mismatches. Nonpalindromic loops were repaired efficiently and with bias toward loop loss. In contrast, the 12-base palindromic loop was repaired with bias toward loop retention, indicating that repair bias depends on loop structure. Among the palindromic loops, repair bias was dependent on loop length, with bias shifting from loop retention to loop loss with increasing loop size. For both palindromic and nonpalindromic loops, repair efficiencies and biases were independent of the general (MSH/MLH) mismatch repair pathway. These results are discussed with respect to the maintenance of large nonpalindromic insertions, and of small and large palindromes, in eukaryotic genomes. (C) 2001 Published by Elsevier Science B.V. C1 Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02129 USA. RP Nickoloff, JA (reprint author), Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. FU NCI NIH HHS [CA54079] NR 86 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD APR 4 PY 2001 VL 485 IS 3 BP 255 EP 265 DI 10.1016/S0921-8777(01)00065-9 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 417MF UT WOS:000167838200008 PM 11267836 ER PT J AU Carbo, N Lopez-Soriano, J Costelli, P Alvarez, B Busquets, S Baccino, FM Quinn, LS Lopez-Soriano, FJ Argiles, JM AF Carbo, N Lopez-Soriano, J Costelli, P Alvarez, B Busquets, S Baccino, FM Quinn, LS Lopez-Soriano, FJ Argiles, JM TI Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: A potential role in body weight control SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE interleukin-15; protein turnover; lipoprotein lipase; lipogenesis; cytokine ID TUMOR-NECROSIS-FACTOR; SKELETAL-MUSCLE; FACTOR-ALPHA; PROTEIN-TURNOVER; GENE-EXPRESSION; BEARING RATS; LIPOPROTEIN-LIPASE; INSULIN-RESISTANCE; LIPID-METABOLISM; CANCER CACHEXIA AB Interleukin (IL)-15 is a cytokine which is highly expressed in skeletal muscle. Cell culture studies have indicated that IL-15 may have an important role in muscle fiber growth and anabolism. However, data concerning the metabolic effects of this cytokine in vivo are lacking. In the present study, IL-15 was administered to adult rats for 7 days. While IL-15 did not cause changes in either muscle mass or muscle protein content, it induced significant changes in the fractional rates of both muscle protein synthesis and degradation, with no net changes in protein accumulation. Additionally, IL-15 administration resulted in a 33% decrease in white adipose tissue mass and a 20% decrease in circulating triacylglycerols; this was associated with a 47% lower hepatic lipogenic rate and a 36% lower plasma VLDL triacylglycerol content. The decrease in white fat induced by IL-15 was in adipose tissue. No changes were observed in the rate of lipolysis as a result of cytokine administration. These findings indicate that IL-15 has significant effects on both protein and lipid metabolism, and suggest that this cytokine may participate in reciprocal regulation of muscle and adipose tissue mass. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, Canc Res Grp, E-08071 Barcelona, Spain. Univ Turin, Dipartimento Med & Oncol Sperimentale, Turin, Italy. CNR, Ctr Immunogenet & Expt Oncol, Turin, Italy. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Amer Lake Div, Tacoma, WA 98493 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Argiles, JM (reprint author), Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, Canc Res Grp, Diagonal 645, E-08071 Barcelona, Spain. EM argiles@porthos.bio.ub.es NR 45 TC 81 Z9 85 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD APR 3 PY 2001 VL 1526 IS 1 BP 17 EP 24 DI 10.1016/S0304-4165(00)00188-4 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 419HE UT WOS:000167942600005 PM 11287118 ER PT J AU Malik, TH Shoichet, SA Latham, P Kroll, TG Peters, LL Shivdasani, RA AF Malik, TH Shoichet, SA Latham, P Kroll, TG Peters, LL Shivdasani, RA TI Transcriptional repression and developmental functions of the atypical vertebrate GATA protein TRPS1 SO EMBO JOURNAL LA English DT Article DE GATA proteins; mammalian development; transcriptional repression; tricho-rhino-phalangeal syndromes; TRPS1 ID ZINC-FINGER PROTEIN; DNA-BINDING PROTEINS; HEART TUBE FORMATION; VENTRAL MORPHOGENESIS; ENDODERM DEVELOPMENT; TARGETED MUTATION; MICE LACKING; GENE; COFACTOR; FOG-2 AB Known vertebrate GATA proteins contain two zinc fingers and are required in development, whereas invertebrates express a class of essential proteins containing one GATA-type zinc finger. We isolated the gene encoding TRPS1, a vertebrate protein with a single GATA-type zinc finger. TRPS1 is highly conserved between Xenopus and mammals, and the human gene is implicated in dominantly inherited tricho-rhino-phalangeal (TRP) syndromes, TRPS1 is a nuclear protein that binds GATA sequences but fails to transactivate a GATA-dependent reporter. Instead, TRPS1 potently and specifically represses transcriptional activation mediated by other GATA factors. Repression does not occur from competition for DNA binding and depends on a C-terminal region related to repressive domains found in Ikaros proteins. During mouse development, TRPS1 expression is prominent in sites showing pathology in TRP syndromes, which are thought to result from TRPS1 haploinsufficiency, We show instead that truncating mutations identified in patients encode dominant inhibitors of wild-type TRPS1 function, suggesting an alternative mechanism for the disease. TRPS1 is the first example of a GATA protein with intrinsic transcriptional repression activity and possibly a negative regulator of GATA-dependent processes in vertebrate development. C1 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. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL55321, R01 HL055321] NR 49 TC 63 Z9 69 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 2 PY 2001 VL 20 IS 7 BP 1715 EP 1725 DI 10.1093/emboj/20.7.1715 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 420AH UT WOS:000167981400023 PM 11285235 ER PT J AU Hafezi-Moghadam, A Thomas, KL Prorock, AJ Huo, YQ Ley, K AF Hafezi-Moghadam, A Thomas, KL Prorock, AJ Huo, YQ Ley, K TI L-selectin shedding regulates leukocyte recruitment SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE inflammation; signaling; trafficking; rolling velocity; ICAM-1 ID ADHESION MOLECULE-1 ICAM-1; ROLLING IN-VIVO; DEFICIENT MICE; P-SELECTIN; NEUTROPHIL ADHESION; T-LYMPHOCYTES; CROSS-LINKING; MAC-1; MIGRATION; VENULES AB The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor alpha -induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration by a lymphocyte function-associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1-dependent mechanism, We examined thr quality of leukocyte rolling and L-selectin-mediated signaling. Blockade of L-selectin shedding significantly reduced the "jerkiness" of leukocyte rolling, defined as the variability of velocity over time. A low level of jerkiness was also observed in the rolling of microbeads conjugated with L-selectin, a model system lacking the mechanism for L-selectin shedding. Inhibition of L-selectin shedding potentiated activation of LFA-1 and Mac-1 induced by L-selectin cross-linking as shown by activation epitope expression and binding of ICAM-1-conjugated beads. We conclude that inhibition of L-selectin shedding increases leukocyte adhesion and transmigration by (a) increasing leukocyte exposure to the inflamed endothelium by decreasing jerkiness and (b) promoting leukocyte activation by outside-in signaling. These observations help to resolve the apparent discrepancy between the minor contribution of L-selectin to rolling and the significant leukocyte recruitment defect in L-selectin knockout mice. C1 Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA. RP Hafezi-Moghadam, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM moghadam@cbr.med.harvard.edu FU NHLBI NIH HHS [HL54136, HL64381] NR 44 TC 144 Z9 150 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 2 PY 2001 VL 193 IS 7 BP 863 EP 872 DI 10.1084/jem.193.7.863 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 420WN UT WOS:000168028400010 PM 11283159 ER PT J AU Romeo, HE Tio, DL Rahman, SU Chiappelli, F Taylor, AN AF Romeo, HE Tio, DL Rahman, SU Chiappelli, F Taylor, AN TI The glossopharyngeal nerve as a novel pathway in immune-to-brain communication: relevance to neuroimmune surveillance of the oral cavity SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE glossopharyngeal nerve transection; lipopolysaccharide; interleukin-1 beta; fever; soft palate; rat ID FETAL ALCOHOL EXPOSURE; TUMOR-NECROSIS-FACTOR; SUBDIAPHRAGMATIC VAGOTOMY; CIRCULATING PYROGENS; SELECTIVE VAGOTOMIES; VAGAL INNERVATION; SICKNESS BEHAVIOR; VAGUS NERVE; RAT; FEVER AB Glossopharyngeal afferents may be the neural channel by which immune challenge of the posterior oral cavity conveys information to the brain, If this is the case, then bilateral transection of the glossopharyngeal nerves (GLOx) should disrupt this communication. Injection of lipopolysaccharide (LPS) or interleukin (IL)-1 beta into the soft palate (ISP) of sham-operated rats induced a dose-related febrile response. GLOx significantly attenuated the febrile response induced by ISP injection of both LPS and IL-IP. In contrast, GLOx did not affect the febrile response when LPS or IL-1 beta were injected intraperitoneally, indicating that the effect of GLOx is not systemic. These results provide experimental evidence for a novel neural pathway for immune-to-brain communication. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. W Los Angeles Healthcare Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Dent, Div Oral Biol, Los Angeles, CA 90095 USA. RP Taylor, AN (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NIAAA NIH HHS [AA09850] NR 53 TC 50 Z9 53 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR 2 PY 2001 VL 115 IS 1-2 BP 91 EP 100 DI 10.1016/S0165-5728(01)00270-3 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 419JW UT WOS:000167946400010 PM 11282158 ER PT J AU Mukherjee, S AF Mukherjee, S TI Drug use - The free market brings AIDS meds to Africa. SO NEW REPUBLIC LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mukherjee, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW REPUBLIC INC PI WASHINGTON PA 1220 19TH ST NW SUITE 600, WASHINGTON, DC 20036 USA SN 0028-6583 J9 NEW REPUBLIC JI New Repub. PD APR 2 PY 2001 VL 224 IS 14 BP 22 EP 23 PG 2 WC Political Science SC Government & Law GA 415BY UT WOS:000167701700014 ER PT J AU Filley, CM Kelly, JP Price, BH AF Filley, CM Kelly, JP Price, BH TI Violence and the brain: An urgent need for research SO SCIENTIST LA English DT Editorial Material C1 Univ Colorado, Sch Med, Boulder, CO 80309 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Inst Rehabil, Chicago, IL USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Filley, CM (reprint author), Univ Colorado, Sch Med, Boulder, CO 80309 USA. NR 1 TC 1 Z9 1 U1 0 U2 1 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD APR 2 PY 2001 VL 15 IS 7 BP 39 EP 39 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 423GQ UT WOS:000168167400023 ER PT J AU Jayaraman, A Yarmush, DM Yarmush, ML Roth, CM AF Jayaraman, A Yarmush, DM Yarmush, ML Roth, CM TI Expression profiling of inflammatory responses in hepatocytes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 57-BTEC BP U462 EP U463 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824802800 ER PT J AU Walton, P Jayaraman, A Stephanopoulos, GN Yarmush, ML Roth, CM AF Walton, P Jayaraman, A Stephanopoulos, GN Yarmush, ML Roth, CM TI Thermodynamics and kinetics of oligonucleotide binding. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MIT, Dept Chem Engn, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Dept Surg Serv, Ctr Engn Med, Boston, MA 02114 USA. EM spwalton@mit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 93-CARB BP U170 EP U170 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700829 ER PT J AU Zinn, WM Sullivan, AM Zotov, N Peters, AS Connelly, MT Singer, JD Block, SD AF Zinn, WM Sullivan, AM Zotov, N Peters, AS Connelly, MT Singer, JD Block, SD TI The effect of medical education on primary care orientation: Results of two national surveys of students' and residents' perspectives SO ACADEMIC MEDICINE LA English DT Article ID GENERAL-INTERNAL-MEDICINE; FAMILY MEDICINE; SCHOOLS; DETERMINANTS; APPLICANTS; CULTURE; CHOICE AB Purpose. To examine changes among a nationally representative sample of students and residents in their orientations toward primary care as reflected in their attitudes toward the psychosocial and technical aspects of medicine and their perceptions of the academic environment fur primary care. Method. Confidential telephone interviews of stratified national probability samples of first- and fourth-year medical students and residents were conducted in 1994 and 1997. The 1997 survey included 219 students and 241 residents who had also been interviewed in 1994. Participants were asked about their attitudes toward addressing psychosocial issues in medicine and their perceptions of faculty and peer attitudes toward primary care. Responses were compared over time and across groups. Results. Between the first and fourth years of medical school, there was a decline over time in students' reported orientations to socioemotional aspects of patient care (61.6% versus 42.7%, p = .001) and their perceptions that working with psychosocial issues of patients made primary care more attractive (56.3% versus 43.5%, p = .01). This pattern continued for 1997 residents (PGY-3), who were even less likely to say that addressing psychosocial issues made primary care more attractive (26.9%). For fourth-year students in 1994 who became PGY-3 residents in 1997, there was an increased perception that non-primary-care house officers and specialty faculty had positive attitudes toward primary care (20.8% versus 33.0%, p = .005; 28.3% versus 45.7%, p < .0001; respectively). Conclusions. Between 1994 and 1997 students and residents perceived a positive shift in the attitudes of peers and faculty toward primary care. During the course of their education and training, however, the students experienced an erosion of their orientations to primary care as they progressed through medical school into residency. C1 Cambridge Hosp, Dept Med, Primary Care Ctr, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Cambridge, MA 02138 USA. Harvard Pilgrim Hlth Care, Brookline, MA USA. Dana Farber Canc Inst, Adult Psychosocial Oncol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Zinn, WM (reprint author), Cambridge Hosp, Dept Med, Primary Care Ctr, 1493 Cambridge St, Cambridge, MA 02139 USA. RI Singer, Judith/B-6846-2008; OI Singer, Judith/0000-0002-5828-4961 NR 20 TC 19 Z9 21 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2001 VL 76 IS 4 BP 355 EP 365 DI 10.1097/00001888-200104000-00014 PG 11 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 422RF UT WOS:000168132500013 PM 11299151 ER PT J AU Sands, BE AF Sands, BE TI Biologicals : principles, techniques and mechanisms of action SO ACTA GASTRO-ENTEROLOGICA BELGICA LA English DT Article; Proceedings Paper CT Conference on Biological Therapies for Inflammatory Bowel Diseases CY JAN 26-27, 2001 CL LEUVEN, BELGIUM ID INFLAMMATORY BOWEL-DISEASE; CROHNS-DISEASE; ULCERATIVE-COLITIS; ESCHERICHIA-COLI; MAINTENANCE TREATMENT; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; THERAPY; MESALAZINE; RESPONSES AB Biological agents for the treatment of IBD are the result of both the explosion of knowledge precipitated by the techniques of molecular biology, and by the ability to use these same techniques to produce agents. Thus, there has been a greatly facilitated translation of basic knowledge into clinical therapy. An astounding number of biologic agents are currently in development for the treatment of IBD and other immune-mediated conditions. These include native microbiologic preparations isolated for beneficial properties, recombinant cytokines and anticytokines, monoclonal antibodies, antisense oligonucleotides, and in the future, somatic gene therapy. This work seeks to describe the principles and techniques of biologic agent development, as well as prime sites of action targeted by these agents. Recent advances in the techniques of molecular biology have made possible unprecedented progress in the treatment of many conditions. The techniques of molecular biology have provided new methods of drug discovery and at the same time have elucidated new therapeutic targets. Most notable has been the progress made in the treatment of chronic inflammatory and immune mediated conditions, including inflammatory bowel disease. This paper is intended to highlight the methodological principles behind biologic agents, methods of discovery and production, and to highlight potential therapeutic targets for these new agents. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. NR 22 TC 2 Z9 2 U1 0 U2 1 PU ASSOC SOC SCIENTIFIQUE MED BELGES PI BRUSSELS PA AVENUE CIRCULAIRE 138 A RINGLAAN, B-1180 BRUSSELS, BELGIUM SN 0001-5644 J9 ACTA GASTRO-ENT BELG JI Acta Gastro-Enterol. Belg. PD APR-JUN PY 2001 VL 64 IS 2 BP 165 EP 169 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 457LU UT WOS:000170139400006 PM 11475127 ER PT J AU Sands, BE AF Sands, BE TI Biological therapies for ulcerative colitis SO ACTA GASTRO-ENTEROLOGICA BELGICA LA English DT Article; Proceedings Paper CT Conference on Biological Therapies for Inflammatory Bowel Diseases CY JAN 26-27, 2001 CL LEUVEN, BELGIUM ID INFLAMMATORY-BOWEL-DISEASE; COTTON-TOP TAMARIN; CROHNS-DISEASE; GROWTH-FACTOR; ESCHERICHIA-COLI; FACTOR-ALPHA; INTERLEUKIN-10; MICE; ANTIBODY; MODEL AB Biological therapies are being increasingly investigated for the treatment of inflammatory bowel disease. However, a great deal more study has been devoted to studies of Crohn's disease rather than ulcerative colitis. Ulcerative colitis, like Crohn's disease, represents an area of high clinical need, particularly for those patients who have disease inadequately responsive to corticosteroids and 5-aminosalicylates. The distinct anatomic distribution of inflammation in ulcerative colitis represents an important model for study, with the entire involved mucosa entirely accessible to endoscopy. In addition, there is an opportunity for local delivery of biologic agents in left-sided disease. Distinct pathogenetic factors in ulcerative colitis raise the possibility of therapies quite different from those used in Crohn's disease. This work describes the current state of knowledge regarding biological therapy in ulcerative colitis. The role of probiotic therapy, and studies of cytokine-directed therapies, therapies targeting adhesion and recruitment, and restitution and repair are described. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. NR 31 TC 5 Z9 5 U1 0 U2 2 PU ASSOC SOC SCIENTIFIQUE MED BELGES PI BRUSSELS PA AVENUE CIRCULAIRE 138 A RINGLAAN, B-1180 BRUSSELS, BELGIUM SN 0001-5644 J9 ACTA GASTRO-ENT BELG JI Acta Gastro-Enterol. Belg. PD APR-JUN PY 2001 VL 64 IS 2 BP 205 EP 209 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 457LU UT WOS:000170139400016 PM 11475137 ER PT J AU Mele, D Schwammenthal, E Torp, H Nesta, F Pedini, I Vandervoort, P Alboni, P Levine, RA AF Mele, D Schwammenthal, E Torp, H Nesta, F Pedini, I Vandervoort, P Alboni, P Levine, RA TI A semiautomated objective technique for applying the proximal isovelocity surface area method to quantitate mitral regurgitation: Clinical studies with the digital flow map SO AMERICAN HEART JOURNAL LA English DT Article ID CONVERGENCE METHOD; ORIFICE AREA; QUANTIFICATION; VOLUME; JET; VALIDATION; VELOCITY; SEVERITY; IMPACT; FIELD AB Background Clinical application of the color Doppler proximal isovelocity surface area (PISA) method to quantify mitral regurgitation (MR) has been limited by the often inaccurate assumption that isovelocity surfaces are hemispheric. This study applied an objective method for selecting the region where the hemispheric geometry holds best on the basis of mathematic analysis of results at different distances from the orifice. We aimed to demonstrate this approach can be applied accurately in the clinical setting and can be semiautomated to promote routine use by extracting velocities from the digital Doppler output and then performing all the calculations automatically. Methods In 75 patients with isolated MR, centerline velocities (V-r) at each distance (r) from the orifice in the proximal Row field were extracted digitally. The automated analysis calculated peak MR flow rates as 2 pir(2)V(r) and plotted these against their respective velocities. The optimal value for peak flow rate was obtained mathematically at the site where the slope of this curve was minimal (least inaccuracy). This value was combined with continuous wave Doppler data to provide regurgitant stroke volume (RSV) and orifice area (ROA), which were compared with quantitative Doppler in 75 patients and angiography in 42. Results RSV and ROA by this optimized, semiautomated PISA method correlated and agreed well with values from quantitative Doppler (y = 0.9 x + 1.9, r = 0.90, standard error of the estimate [SEE] = 8.1 mL, mean difference = -0.7 +/- 8.5 mi for RSV; y = 0.9 x + 0.02, r = 0.90, SEE = 0.048 cm(2), mean difference = -0.005 +/- 0.1 cm(2) for ROA) and correlated well with angiography (p = 0.90 for both RSV and ROA). Conclusions This objective PISA method for quantifying MR is accurate in the clinical setting and has been semiautomated by use of analysis of digital velocity data to provide a rapid and practical technique suitable to facilitate more extensive application in routine practice. C1 Arcispedale S Anna, Div Cardiol, I-44100 Ferrara, Italy. Hosp Cento, Cento, Italy. Massachusetts Gen Hosp, Noninvas Cardiac Lab, Boston, MA 02114 USA. Univ Trondheim, Dept Bioengn, Trondheim, Norway. RP Mele, D (reprint author), Arcispedale S Anna, Div Cardiol, Corso Giovecca 203, I-44100 Ferrara, Italy. NR 24 TC 4 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2001 VL 141 IS 4 BP 653 EP 660 DI 10.1067/mhj.2001.113392 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 419JK UT WOS:000167945400022 PM 11275934 ER PT J AU Rubenstein, MH Sheynberg, BV Harrell, LC Schunkert, H Bazari, H Palacios, IF AF Rubenstein, MH Sheynberg, BV Harrell, LC Schunkert, H Bazari, H Palacios, IF TI Effectiveness of and adverse events after percutaneous coronary intervention in patients with mild verses severe renal failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC-HEMODIALYSIS; ANGIOPLASTY; COMPLICATIONS; REGISTRY; TERM AB Patients with renal failure undergoing percutaneaus coronary intervention (PCI) experience reduced procedural success rates and increased in-hospital and long-term follow-up major adverse cardiac events. This study was designed to determine whether the severity of preprocedural renal failure influences the outcomes of patients with renal failure undergoing PCI. We compared the immediate and long-term outcomes of 192 patients with mild renal failure (creatinine 1.6 to 2.0 mg/dl, mean 1.76) with those of 131 patients with severe renal failure (creatinine >2.0 mg/dl, mean 2.90), selected from 3,334 consecutive patients undergoing PCI between 1994 and 1997. Although the overall population with renal failure represents a high-risk group, the severe renal failure cohort had a higher incidence of hypertension, multivessel disease, prior coronary bypass surgery, vascular disease, and congestive heart failure tall p values <0.05), yet had similar angiographic characteristics. procedural success was higher in the group with severe renal failure (93.7% vs 87.7%, p = 0.04). There were no statistically significant differences in in-hospital mortality (11.5% vs 9.9%, p = 0.7), Q-wave myocardial infarction (0.5% vs 0%, p = 0.4), emergent bypass surgery (0% vs 0%, p = 1.0), and in-hospital major adverse cardiac events (11.5% vs 9.9%, p = 0.7) between the mild and severe renal groups, respectively. Kaplan-Meier analyses showed no statistically significant difference in long-term survival (log rank test, p 0.1) or event-free survival (log rank test, p = 0.3) between the 2 groups. Finally, creatinine was not identified as an independent predictor of in-hospital or long-term follow-up major adverse cardiac events. In our high-risk papulation, patients with mild renal insufficiency undergoing PCI experience major adverse outcomes in the hospital and at long-term follow-up similar to those of patients with severe renal failure. <(c)> 2001 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Catherizat Labs, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Catherizat Labs, Dept Med, Cardiac Unit, Boston, MA 02114 USA. NR 9 TC 44 Z9 44 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2001 VL 87 IS 7 BP 856 EP 860 DI 10.1016/S0002-9149(00)01526-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 415UE UT WOS:000167741300008 PM 11274940 ER PT J AU Sharma, GVRK Frisbie, JH Tow, DE Yalla, SV Khuri, SF AF Sharma, GVRK Frisbie, JH Tow, DE Yalla, SV Khuri, SF TI Circadian and circannual rhythm of nonfatal pulmonary embolism SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SUDDEN CARDIAC DEATH; MYOCARDIAL-INFARCTION; ONSET; THROMBOEMBOLISM; STROKE AB Because circadian and circannual rhythms have not been reported in nonfatal pulmonary embolism (PE), we examined this issue in 89 patients who sustained PE during their hospitalization for other conditions. We found that nonfatal PE follows a circadian and circannual pattern with predominant occurrence in the morning hours and the fall-winter seasons, respectively. C1 Dept Vet Affairs Med Ctr, Med Serv, W Roxbury, MA USA. Dept Vet Affairs Med Ctr, Nucl Med Serv, W Roxbury, MA USA. Dept Vet Affairs Med Ctr, Spinal Cord Injury Serv, W Roxbury, MA USA. Dept Vet Affairs Med Ctr, Surg Serv, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sharma, GVRK (reprint author), Vet Affairs Med Ctr, Div Cardiol, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 14 TC 17 Z9 18 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2001 VL 87 IS 7 BP 922 EP + DI 10.1016/S0002-9149(00)01542-3 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 415UE UT WOS:000167741300024 PM 11274956 ER PT J AU Januzzi, JL Movsowitz, HD Choi, J Abernethy, WB Isselbacher, EM AF Januzzi, JL Movsowitz, HD Choi, J Abernethy, WB Isselbacher, EM TI Significance of recurrent pain in acute type B aortic dissection SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MANAGEMENT AB Among 53 patients with initially uncomplicated acute type B aortic dissection, recurrent pain alone did not predict complications or adverse outcome. These data suggest that in the absence of evidence of clinical or radiographic complications, the course of patients with recurrent discomfort after type B aortic dissection may be more benign than previously thought, and that symptoms of recurrent pain alone map not necessarily be an indication fur urgent aortic surgery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thorac Aorta Ctr, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 15 Parkman St,WAC 469, Boston, MA 02114 USA. NR 9 TC 8 Z9 8 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2001 VL 87 IS 7 BP 930 EP + DI 10.1016/S0002-9149(00)01545-9 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 415UE UT WOS:000167741300027 PM 11274959 ER PT J AU Obasaju, C Manola, J Hudes, GR Khandekar, JD Citrin, DL Carbone, P Trump, DL AF Obasaju, C Manola, J Hudes, GR Khandekar, JD Citrin, DL Carbone, P Trump, DL TI Phase II evaluation of menogaril in advanced prostate cancer - Eastern Cooperative Oncology Group EST P-A885 SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE prostate cancer; menogaril; chemotherapy ID WEEKLY DOXORUBICIN; ADRIAMYCIN AB Menogaril is a semisynthetic anthracycline that is less cardiotoxic than doxorubicin in a preclinical model. We conducted a phase II trial to determine the activity of menogaril in hormone-refractory prostate cancer. Between October 1985 and November 1987, 32 eligible patients were enrolled and were divided into good- and poor-risk categories, the latter being defined by prior radiotherapy to less than one third of the marrow-containing skeleton. Good-risk patients received a starting dose of 200 mg/m(2) by 60-minute IV infusion, whereas the poor-risk patients received 160 mg/m(2). Treatment was repeated every 3 weeks until disease progression Menogaril caused leukopenia in 90% of patients, of whom 47% had grade m or TV toxicity, Thrombocytopenia was uncommon and mild, with only three patients (9%) experiencing grade II toxicity. Nonhematologic toxicity included mucositis (9%), and mild weight loss in 33% of patients. Nine patients (28%) had stable disease of 3 or more months' duration. Then were no objective partial or complete responses. The median time to progression for the entire group was 10 weeks, and the median survival time for all patients was 24 weeks. Because of appreciable toxicity and limited antitumor activity, further study of menogaril cannot be recommended in hormone-refractory prostate cancer. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Evanston Northwestern Hlth Care, Evanston, IL USA. Northwestern Univ, Sch Med, Chicago, IL USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. RP Hudes, GR (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [CA66636, CA27525, CA23318, CA21076, CA17145, CA21115, CA59307] NR 10 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2001 VL 24 IS 2 BP 150 EP 154 DI 10.1097/00000421-200104000-00011 PG 5 WC Oncology SC Oncology GA 423PQ UT WOS:000168186300011 PM 11319290 ER PT J AU Seage, GR Holte, SE Metzger, D Koblin, BA Gross, M Celum, C Marmor, M Woody, G Mayer, KH Stevens, C Judson, FN McKirnan, D Sheon, A Self, S Buchbinder, SP AF Seage, GR Holte, SE Metzger, D Koblin, BA Gross, M Celum, C Marmor, M Woody, G Mayer, KH Stevens, C Judson, FN McKirnan, D Sheon, A Self, S Buchbinder, SP TI Are US populations appropriate for trials of human immunodeficiency virus vaccine? The HIVNET Vaccine Preparedness Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; HIV infections; incidence; vaccination; vaccines ID INJECTION-DRUG USERS; NEW-YORK-CITY; EFFICACY TRIALS; BISEXUAL MEN; COMMUNITY CONCERNS; UNITED-STATES; RISK BEHAVIOR; SOCIAL-ISSUES; INFECTION; SEROCONVERSION AB Questions exist about whether testing of preventive human immunodeficiency virus (HIV)-1 vaccines, which will require rapid recruitment and retention of cohorts with high HIV-1 seroincidence, is feasible in the United States. A prospective cohort study was conducted in 1995-1997 among 4,892 persons at high risk for HIV infection in nine US cities. At 18 months, with an 88% retention rate, 90 incident HIV-1 infections were observed (1.31/100 person-years (PY), 95% confidence interval (CI): 1.06, 1.61). HIV-I seroincidence rates varied significantly by baseline eligibility criteria-1.55/100 PY among men who had sex with men, 0.38/100 PY among male intravenous drug users, 1.24/100 PY among female intravenous drug users, and 1.13/100 PY among women at heterosexual risk-and by enrollment site, from 0.48/100 PY to 2.18/100 PY. HIV-1 incidence was highest among those men who had sex with men who reported unprotected anal intercourse (2.01/100 PY, 95% CI: 1.54, 2.63), participants who were definitely willing to enroll in an HIV vaccine trial (1.96/100 PY, 95% CI: 1.41, 2.73), and women who used crack cocaine (1.62/100 PY, 95% CI: 0.92, 2.85). Therefore, cohorts with HIV-1 seroincidence rates appropriate for HIV-1 vaccine trials can be recruited, enrolled, and retained. C1 Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. ABT Associates Inc, Cambridge, MA 02138 USA. Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent SCHARP, Seattle, WA 98104 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Penn, VA Ctr Studies Addict, Philadelphia, PA 19104 USA. Univ Penn, VA Ctr Studies Addict, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. New York Blood Ctr, Lab Epidemiol, New York, NY 10021 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. NYU, Sch Med, Dept Environm Med, New York, NY USA. NYU, Sch Med, Dept Med, New York, NY USA. Fenway Community Hlth Ctr, Dept Res, Providence, RI USA. Brown Univ, Denver, CO USA. Denver Dept Publ Hlth, Denver, CO USA. Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. Howard Brown Hlth Ctr, Chicago, IL USA. Univ Michigan, Ann Arbor, MI 48109 USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. RP Seage, GR (reprint author), Harvard Univ, Dept Epidemiol, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. OI Marmor, Michael/0000-0001-6605-2661 FU NCRR NIH HHS [M01RR00096]; NIAID NIH HHS [AI 27742, N01-AI-35176, N01-AI-45200] NR 49 TC 84 Z9 85 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2001 VL 153 IS 7 BP 619 EP 627 DI 10.1093/aje/153.7.619 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 419CD UT WOS:000167931000001 PM 11282787 ER PT J AU El-Serag, HB Lee, P Buchner, A Inadomi, JM Gavin, M McCarthy, DM AF El-Serag, HB Lee, P Buchner, A Inadomi, JM Gavin, M McCarthy, DM TI Lansoprazole treatment of patients with chronic idiopathic laryngitis: A placebo-controlled trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; POSTERIOR LARYNGITIS; CHRONIC COUGH; OMEPRAZOLE; REPRODUCIBILITY; ESOPHAGITIS; HOARSENESS; LARYNGEAL; SYMPTOMS; ACID AB OBJECTIVE: Previous uncontrolled studies suggested a therapeutic benefit for treating gastroesophageal reflux disease (GERD) among patients with laryngitis. The present study is the first randomized, placebo-controlled, double-blind study of gastric acid suppression among patients with laryngitis in the United States. METHODS: Patients diagnosed with idiopathic chronic laryngitis were randomized to receive either lansoprazole 30 mg p.o. b.i.d. or a matching placebo for 3 months. Before randomization, all patients underwent upper endoscopy, dual probe ambulatory 24-h esophageal pH-metry, and laryngoscopy, as well as completing a symptom questionnaire for GERD and laryngitis. The primary outcome of treatment was the complete resolution of laryngeal symptoms. RESULTS: A total of 22 patients with symptoms and signs of chronic laryngitis were enrolled, 20 of whom completed the study. At baseline, there were no significant differences between the two groups with regards to GERD symptoms, erosive esophagitis, proximal and distal esophageal pH-metry, or laryngeal signs and symptoms. In an intention-to-treat analysis, six patients in the lansoprazole group (50%) and only one patient (10%) in the placebo group achieved a complete symptomatic response, p = 0.04. Apart from receiving lansoprazole, there were no significant differences between responders and nonresponders in any of baseline esophageal or laryngeal signs and symptoms. CONCLUSIONS: Empirical treatment with lansoprazole is efficacious in relieving symptoms of laryngitis compared to placebo. Such treatment can be considered as a first-line option in managing patients with idiopathic chronic laryngitis. (Am J Gastroenterol 2001;96:979-983. (C) 2001 by Am. Coll. of Gastroenterology). C1 Houston Vet Affairs Med Ctr, Div Gastroenterol, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Div Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Albuquerque VA Med Ctr, Dept Otolaryngol, Albuquerque, NM USA. Albuquerque VA Med Ctr, Div Gastroenterol, Albuquerque, NM USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Ann Arbor VA Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. Ann Arbor VA Med Ctr, Div Hlth Serv Res, Ann Arbor, MI USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Div Gastroenterol, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. RI Inadomi, John/A-6221-2014 OI Inadomi, John/0000-0001-6776-8661 NR 24 TC 106 Z9 119 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2001 VL 96 IS 4 BP 979 EP 983 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 422RR UT WOS:000168133500013 PM 11316215 ER PT J AU Lee, C Gisselsson, D Jin, C Nordgren, A Ferguson, DO Blennow, E Fletcher, JA Morton, CC AF Lee, C Gisselsson, D Jin, C Nordgren, A Ferguson, DO Blennow, E Fletcher, JA Morton, CC TI Limitations of chromosome classification by multicolor karyotyping SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID IN-SITU HYBRIDIZATION; HUMAN BREAST-CANCER; MULTIPLEX-FISH; IDENTIFICATION; REARRANGEMENTS AB Multicolor karyotyping technologies, such as spectral karyotyping (SKY) (Schrock et al. 1996; Liyanage et al. 1996) and multiplex (M-) FISH (Speicher et al. 1996), have proved to be extremely useful in prenatal, postnatal, and cancer cytogenetics. However, these technologies have inherent limitations that, in certain situations, may result in chromosomal misclassification. In this report, we present nine cases, which fall into five categories, in which multicolor karyotyping has produced erroneous interpretations. Most errors appear to have a similar mechanistic basis. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden. Karolinska Inst, Karolinska Hosp, Dept Mol Med, S-10401 Stockholm, Sweden. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RI Nordgren, Ann/N-4057-2013 OI Nordgren, Ann/0000-0003-3285-4281 NR 20 TC 54 Z9 63 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2001 VL 68 IS 4 BP 1043 EP 1047 DI 10.1086/319503 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 414KQ UT WOS:000167666000024 PM 11222105 ER PT J AU Han, WK Sapirstein, A Bonventre, JV AF Han, WK Sapirstein, A Bonventre, JV TI Role of phospholipase A(2)s in hydrogen peroxide-induced arachidonic acid release in murine mesangial cell. SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Anesthesia, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2001 VL 37 IS 4 MA 29 BP A18 EP A18 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 453FG UT WOS:000169905400062 ER PT J AU Yu, EI Glassman, PA Asch, SM Paige, NM Passman, LJ Shekelle, PG AF Yu, EI Glassman, PA Asch, SM Paige, NM Passman, LJ Shekelle, PG TI Cost-sharing for prescriptions of sildenafil and finasteride: A case study in veteran patients SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID WILLINGNESS-TO-PAY; MANAGED CARE; LIFE; VIAGRA AB Objective: To evaluate patients' willingness to share the costs of 2 medications (often described as "lifestyle medicdtions"): sildenafil for erectile dysfunction and finasteride Tor hair loss, which are not routinely covered by the Department of Veterans Affairs (VA) healthcare system. Study Design: Self-administered, anonymous survey. Patients and Methods: Adult men (n = 339) were recruited from waiting rooms for primary care or erectile dysfunction clinic appointments at 2 Los Angeles VA facilities. Results: Participants with self-reported need were analyzed separately for finasteride (primary care patients only) and sildenafil (both primary care and erectile dysfunction clinic patients). The mean age of the participants was 56 and 60 years for the finasteride and sildenafil groups, respectively. Mean annual household income for both groups was under $10,000. Respondents reported a mean willingness to cost share $4.20 for a 30-day prescription of daily finasteride (VA wholesale cost = $27) and $5.40 for 4 sildenafil pills (VA wholesale cost = $20). In the multivariate analysis, higher income (P = .002) and increasing self-reported need for medication(P = .04) were associated with increased willingness to cost-share for finasteride after controlling for age, race/ethnicity, insured status, comorbid conditions, and type of clinic. In addition, younger age (P = .01) was associated with greater willingness to cost-share for sildenafile. Conclusions: In this low-income veteran population, patients with a sell-reported need for sildenafil and finasteride would be willing to make a higher copayment than the current VA maximum copayment of $2.00 per 30-day prescription, if these medicines were made available. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Yu, EI (reprint author), 11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. EM emily.yu@med.va.gov NR 18 TC 5 Z9 5 U1 0 U2 0 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 2001 VL 7 IS 4 BP 345 EP 353 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 420PK UT WOS:000168013200003 PM 11310190 ER PT J AU Knapp, HH Schrott, H Ma, P Knopp, R Chin, B Gaziano, JM Donovan, JM Burke, SK Davidson, MH AF Knapp, HH Schrott, H Ma, P Knopp, R Chin, B Gaziano, JM Donovan, JM Burke, SK Davidson, MH TI Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; AVERAGE CHOLESTEROL LEVELS; ARTERY DISEASE; RISK-FACTORS; BILE-ACID; LOVASTATIN; THERAPY; ATHEROSCLEROSIS; PRAVASTATIN; PREVENTION AB PURPOSE: To examine the efficacy and safety of colesevelam hydrochloride, a novel, nonsystemic, lipid-lowering agent, when coadministered with starting doses of simvastatin in a multicenter, randomized, double-blind, placebo-controlled trial. PATIENTS AND METHODS: Subjects with hypercholesterolemia (plasma low density lipoprotein [LDL] cholesterol level > 160 mg/dL and triglyceride level less than or equal to 300 mg/dL) were randomly assigned to receive daily doses of placebo (n = 33), colesevelam 3.8 g (recommended dose, n = 37), simvastatin 10 mg(n = 35), colesevelam 3.8 g with simvastatin 10 mg(n = 34), colesevelam 2.3 g (low dose, n = 36), simvastatin 20 mg (n = 39), or colesevelam 2.3 g with simvastatin 20 mg (n = 37), for 6 weeks. RESULTS: Mean LDL cholesterol levels decreased relative to baseline in the placebo group (P < 0.05) and in all active treatment groups (P < 0.0001). For groups treated with combination therapy, the mean reduction in LDL cholesterol level was 42% (-80 mg/dL; P (0.0001 compared with baseline), which exceeded the reductions for simvastatin 10 mg (-26%, -48 mg/dL) or 20 mg (-34%, -61 mg/dL) alone, or for colesevelam 2.3 g (-8%, -17 mg/dL) or 3.8 g (-16%, -31 mg/dL) alone (P < 0.001). The effects of combination therapy on serum HDL cholesterol and triglyceride levels were similar to those for simvastatin alone. Side effects were similar among treatment groups, and there were no clinically important changes in laboratory parameters. CONCLUSION: Coadministration of colesevelam and simvastatin was effective and well tolerated, providing additive reductions in LDL cholesterol levels compared with either agent alone. <(c)> 2001 by Excerpta Medica, Inc. C1 GelTex Pharmaceut Inc, Waltham, MA 02451 USA. Univ Iowa, Lipid Res Clin, Iowa City, IA USA. Bridgeland Med, Calgary, AB, Canada. NW Lipid Res Ctr, Seattle, WA USA. Long Isl Jewish Med Ctr, Manhasset, NY USA. VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Chicago Ctr Clin Res, Chicago, IL USA. RP Donovan, JM (reprint author), GelTex Pharmaceut Inc, 153 2nd Ave, Waltham, MA 02451 USA. NR 35 TC 126 Z9 133 U1 1 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR 1 PY 2001 VL 110 IS 5 BP 352 EP 360 DI 10.1016/S0002-9343(01)00638-6 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 416GL UT WOS:000167771900004 PM 11286949 ER PT J AU Lansberg, MG Thijs, VN O'Brien, MW Ali, JO de Crespigny, AJ Tong, DC Moseley, ME Albers, GW AF Lansberg, MG Thijs, VN O'Brien, MW Ali, JO de Crespigny, AJ Tong, DC Moseley, ME Albers, GW TI Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; MAGNETIC-RESONANCE; TIME-COURSE; EMBOLIC STROKE; BRAIN ISCHEMIA; MRI; PERFUSION; MODEL; INFARCTION; RAT AB BACKGROUND AND PURPOSE: Serial study of such MR parameters as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), ADC with fluid-attenuated inversion recovery (ADC(FLAIR)), and T2-weighted imaging may provide information on the pathophysiological mechanisms of acute ischemic stroke. Our goals were to establish the natural evolution of MR signal intensity characteristics of acute ischemic lesions and to assess the potential of using specific MR parameters to estimate lesion age, METHODS: Five serial echo-planar DWI studies with and without an inversion recovery pulse were performed in 27 patients with acute stroke, The following lesion characteristics were studied: 1) conventional ADC (ADC(CONV)); 2) ADC(FLAIR); 3) DWI Signal intensity (SIDWI); 4) T2-weighted signal intensity (SIT2), and 5) FLAIR signal intensity (SIFLAIR), RESULTS: The lesion ADC(CONV) gradually increased from low values during the first week to pseudonormal during the second week to supranormal thereafter, The lesion ADCFLAIR showed the same pattern of evolution but with lower absolute values. A low ADC value indicated, with good sensitivity (88%) and specificity (90%), that a lesion was less than 10 days old, All signal intensities remained high throughout follow-up, SIDWI showed no significant change during the first week but decreased thereafter. SIT2 initially increased, decreased slightly during week 2, and again increased after 14 days. SIFLAIR showed the same initial increase as the SIT2 but remained relatively stable thereafter. CONCLUSION: Our findings further clarify the time course of stroke evolution on MR parameters and indicate that the ADC map may be useful for estimating lesion age, Application of an inversion recovery pulse results in lower, potentially more accurate, absolute ADC values. C1 UZ Gasthuisberg, Dept Neurol, Louvain, Belgium. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, MGH NMR Ctr, Charlestown, MA USA. RP Albers, GW (reprint author), Stanford Stroke Ctr, 701 Welch Rd,Bldg B,Suite 325, Palo Alto, CA 94304 USA. RI Thijs, Vincent/C-3647-2009 OI Thijs, Vincent/0000-0002-6614-8417 FU NINDS NIH HHS [5R01NS35959, 5R01NS34866] NR 42 TC 130 Z9 143 U1 0 U2 8 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2001 VL 22 IS 4 BP 637 EP 644 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 423CA UT WOS:000168156800009 PM 11290470 ER PT J AU Feiwell, RJ Besmertis, L Sarkar, R Saloner, DA Rapp, JH AF Feiwell, RJ Besmertis, L Sarkar, R Saloner, DA Rapp, JH TI Detection of clinically silent infarcts after carotid endarterectomy by use of diffusion-weighted imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Neuroradiology CY APR, 2000 CL ATLANTA, GEORGIA SP Amer Soc Neuroradiol ID MICROEMBOLI; ISCHEMIA; BRAIN; RISK; MRI AB BACKGROUND AND PURPOSE: Intraprocedural transcranial Doppler sonography has identified multiple microembolic events during and immediately after carotid endarterectomy (CEA) or angioplasty, yet the rate of clinically evident stroke is small. To determine the significance of the transcranial Doppler sonography findings, we examined patients by use of diffusion-weighted imaging and fluid-attenuated inversion recovery MR imaging before and immediately after CEA for evidence of clinically silent ischemic events. METHODS: Twenty-five patients with atherosclerotic disease of the carotid arteries underwent diffusion-weighted imaging and fluid-attenuated inversion recovery MR imaging performed, on average, 3 days before and 12 hours after CEA, Diffusion-weighted images were acquired in three orthogonal directions at b = 900, Pre- and postoperative neurologic examinations mere performed by the same physician. RESULTS: After endarterectomy, 4.0% of the patients (one of 25 patients) showed a single, cortical focus of restricted diffusion and new fluid-attenuated inversion recovery hyperintensity, measuring <1 cm in diameter, ipsilateral to the CEA, The postoperative neurologic examination showed no change in status from the preoperative baseline state. This patient had an intraoperative course complicated by the development of a large luminal thrombus, necessitating thrombectomy, CONCLUSION: The use of diffusion-weighted imaging may serve to improve conspicuity of clinically silent infarcts after CEA, An important next step is to determine the risk factors that predispose to detectable parenchymal ischemic events. C1 Univ Calif San Francisco, Neuroradiol Sect, San Francisco, CA 94143 USA. SAn Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Feiwell, RJ (reprint author), Univ Calif San Francisco, Neuroradiol Sect, 505 Parnassus Ave,Room L371, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HL56307] NR 16 TC 44 Z9 45 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2001 VL 22 IS 4 BP 646 EP 649 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 423CA UT WOS:000168156800010 PM 11290471 ER PT J AU Castro, MA Shipp, TD Castro, EE Ouzounian, J Rao, P AF Castro, MA Shipp, TD Castro, EE Ouzounian, J Rao, P TI The use of helical computed tomography in pregnancy for the diagnosis of acute appendicitis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE helical computed tomography in pregnancy; acute appendicitis ID CT; SONOGRAPHY AB OBJECTIVE: Accurate diagnosis of acute appendicitis in pregnancy by clinical evaluation is difficult. A safe, reliable test was sought to decrease a delay in diagnosis and to avoid unnecessary invasive procedures. A helical or spiral computed tomographic technique has proven to be a very accurate test in the nonobstetric population for the identification of acute appendicitis. We report its use in pregnant patients with suspected acute appendicitis. STUDY DESIGN: All pregnant patients who were undergoing helical computed tomograpby at our institution from April 1997 to February 1998 for the suspected clinical diagnosis of acute appendicitis were retrospectively reviewed. Helical computed tomography was performed by standard departmental protocol. A positive study was reported if an enlarged appendix, which did not fill with contrast material, was present with periappendiceal inflammatory changes. Outcomes were determined by the results of surgery and pathologic examination or clinical follow-up. RESULTS: Seven patients were identified in the study period. Two patients had positive findings on helical computed tomography, and acute appendicitis was confirmed at laparotomy and by pathologic inspection. There were no further prenatal complications and both patients delivered at term. Five patients bad a normal-appearing appendix on helical computed tomography, and all of these patients had resolution of their pain and symptoms. CONCLUSION: Helical computed tomography appears to be a useful, noninvasive test to accurately diagnose acute appendicitis in pregnancy. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Kaiser Permanente, Dept Obstet & Gynecol, Baldwin Pk, CA USA. RP Castro, MA (reprint author), Univ Wisconsin, Sch Med, MCC, Sinai Samaritan Med Ctr,Dept OB GYN, 5A,POB 342, Milwaukee, WI 53201 USA. NR 15 TC 36 Z9 39 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2001 VL 184 IS 5 BP 954 EP 957 DI 10.1067/mob.2001.111721 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 426FA UT WOS:000168338100037 PM 11303204 ER PT J AU Miserocchi, E Baltatzis, S Foster, CS AF Miserocchi, E Baltatzis, S Foster, CS TI Ocular features associated with anticardiolipin antibodies: A descriptive study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PRIMARY ANTIPHOSPHOLIPID SYNDROME; SYSTEMIC LUPUS-ERYTHEMATOSUS; CLINICAL-SIGNIFICANCE; DISEASE; ANTICOAGULANT; THROMBOSIS; PREVALENCE; DISORDERS AB PURPOSE: To evaluate ocular features in patients presenting with inflammation in the presence of anti-cardiolipin antibodies. METHODS: A descriptive study of 13 patients presenting with idiopathic ocular inflammation involving anterior and posterior segment was performed. Patients were followed for a mean follow-up of 22 months (range, 1 to 125). A comprehensive report of ocular involvement, including visual symptoms, visual acuity, clinical characteristics, funduscopic and fluorangiographic features, was reported. Systemic associated symptoms were analyzed. Laboratory investigations included anticardiolipin antibody titers and isotypes, presence of other autoantibodies, and markers of immune system activation. RESULTS: The most common ocular symptom at presentation was blurred vision (eight patients) followed by redness and pain(three patients) and visual loss(two patients). Anterior segment abnormalities, including iritis (eight patients) scleritis (two patients) and filamentary keratitis (one patient), were present in 76% of patients, whereas the most represented feature of posterior involvement was retinal vasculitis (60%) followed by vitritis (38%), retinal detachment (15%), posterior scleritis (7%), and central retinal artery occlusion (7%). All patients had abnormal titers of anticardiolipin antibodies, predominantly IgG isotype; six had markers of immune system activation. CONCLUSIONS: Although posterior pole disease is more commonly associated with anticardiolipin antibodies, the anterior segment can also be involved with a wide spectrum of features. Scleritis has never been previously described as associated with anticardiolipin antibodies. Systemic symptoms are frequently present in association with ocular disease. (Am J Ophthalmol 2001;131: 451-456, (C) 2001 by Elsevier Science Inc. All rights reserved). C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Uveitis & Immunol Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Uveitis & Immunol Serv, 243 Charles St, Boston, MA 02114 USA. NR 28 TC 29 Z9 32 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2001 VL 131 IS 4 BP 451 EP 456 DI 10.1016/S0002-9394(00)00884-9 PG 6 WC Ophthalmology SC Ophthalmology GA 418YY UT WOS:000167923700008 PM 11292408 ER PT J AU Sweadner, KJ Feschenko, MS AF Sweadner, KJ Feschenko, MS TI Predicted location and limited accessibility of protein kinase A phosphorylation site on Na-K-ATPase SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE adenosine 3 ',5 '-cyclic monophosphate; crystal structure ID NA,K-ATPASE ALPHA-SUBUNIT; CATALYTIC SUBUNIT; SARCOPLASMIC-RETICULUM; TRANSMEMBRANE ORGANIZATION; IMMUNOELECTRON MICROSCOPY; EXTRACELLULAR SURFACE; TRANSPORTING ATPASE; CRYSTAL-STRUCTURE; CROSS-LINKING; NA+/K+-ATPASE AB Regulation of Na-K-ATPase by cAMP-dependent protein kinase occurs in a variety of tissues. Phosphorylation of the enzyme's catalytic subunit at a classical phosphorylation consensus motif has been observed with purified enzyme. Demonstration of phosphorylation at the same site in normal living cells or tissues has been more difficult, however, making it uncertain that the Na-K-ATPase is a direct physiological substrate of the kinase. Recently, the structure of the homologous sarco( endo) plasmic reticulum Ca-ATPase (SERCA1a) has been determined at 2.6 Angstrom resolution (Toyoshima C, Nakasako M, Nomura H, and Ogawa H. Nature 405: 647-655, 2000.), and the Na-K-ATPase should have the same fold. Here, the Na-K-ATPase sequence has been aligned with the Ca-ATPase structure to examine the predicted disposition of the phosphorylation site. The location is close to the membrane and partially buried by adjacent loops, and the site is unlikely to be accessible to the kinase in this conformation. Conditions that may expose the site or further bury it are discussed to highlight the issues facing future research on regulation of Na-K-ATPase by cAMP-dependent pathways. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01 HL-36271]; NINDS NIH HHS [R01 NS-27653] NR 60 TC 36 Z9 36 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2001 VL 280 IS 4 BP C1017 EP C1026 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 410QX UT WOS:000167451600031 PM 11245618 ER PT J AU Yan, WT Sunavala, G Rosenzweig, S Dasso, M Brand, JG Spielman, AI AF Yan, WT Sunavala, G Rosenzweig, S Dasso, M Brand, JG Spielman, AI TI Bitter taste transduced by PLC-beta(2)-dependent rise in IP3 and alpha-gustducin-dependent fall in cyclic nucleotides SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE taste transduction; denatonium; second messenger; rapid kinetics; taste receptors; inositol 1,4,5-trisphosphate; phospholipase C ID PHOSPHOLIPASE-C; RECEPTOR-CELLS; INOSITOL 1,4,5-TRISPHOSPHATE; FUNGIFORM PAPILLA; SWEET TASTE; SUBSTANCES; STIMULI; MECHANISMS; SACCHARIN; PATHWAYS AB Current evidence points to the existence of multiple processes for bitter taste transduction. Previous work demonstrated involvement of the polyphosphoinositide system and an alpha -gustducin (G alpha (gust))-mediated stimulation of phosphodiesterase in bitter taste transduction. Additionally, a taste-enriched G protein gamma -subunit, G gamma (13), colocalizes with G alpha (gust) and mediates the denatonium-stimulated production of inositol 1,4,5-trisphosphate (IP3). Using quench-flow techniques, we show here that the bitter stimuli, denatonium and strychnine, induce rapid (50-100 ms) and transient reductions in cAMP and cGMP and increases in IP3 in murine taste tissue. This decrease of cyclic nucleotides is inhibited by G alpha (gust) antibodies, whereas the increase in IP3 is not affected by antibodies to G alpha (gust). IP3 production is inhibited by antibodies specific to phospholipase C-beta (2) (PLC-beta (2)), a PLC isoform known to be activated by G beta gamma -subunits. Antibodies to PLC-beta (3) or to PLC-beta (4) were without effect. These data suggest a transduction mechanism for bitter taste involving the rapid and transient metabolism of dual second messenger systems, both mediated through a taste cell G protein, likely composed of G alpha (gust)/beta/gamma (13), with both systems being simultaneously activated in the same bitter-sensitive taste receptor cell. C1 NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, Div Biol Sci Med & Surg, New York, NY 10010 USA. Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Spielman, AI (reprint author), NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, Div Biol Sci Med & Surg, 345 E 24th St, New York, NY 10010 USA. FU NIDCD NIH HHS [DC-00356, DC-03969]; NIDCR NIH HHS [DE-10754] NR 59 TC 78 Z9 79 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2001 VL 280 IS 4 BP C742 EP C751 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 410QX UT WOS:000167451600002 PM 11245589 ER PT J AU Baker, AJ Redfern, CH Harwood, MD Simpson, PC Conklin, BR AF Baker, AJ Redfern, CH Harwood, MD Simpson, PC Conklin, BR TI Abnormal contraction caused by expression of G(i)-coupled receptor in transgenic model of dilated cardiomyopathy SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE signaling; calcium; G proteins; mouse ID DESIGNED G(I)-COUPLED RECEPTOR; HEART-FAILURE; CONDITIONAL EXPRESSION; G-PROTEINS; ALPHA; FORCE; MICE AB Although increased G(i) signaling has been associated with dilated cardiomyopathy in humans, its role is not clear. Our goal was to determine the effects of chronically increased G(i) signaling on myocardial function. We studied transgenic mice that expressed a G(i)-coupled receptor (Ro1) that was targeted to the heart and regulated by a tetracycline-controlled expression system. Ro1 expression for 8 wk resulted in abnormal contractions of right ventricular muscle strips in vitro. Ro1 expression reduced myocardial force by >60% (from 35 +/- 3 to 13 +/- 2 mN/mm(2), P< 0.001). Nevertheless, sensitivity to extracellular Ca2+ was enhanced. The extracellular [Ca2+] resulting in half-maximal force was lower with Ro1 expression compared with control (0.41 +/- 0.05 vs. 0.88 +/- 0.05 mM, P< 0.001). Ro1 expression slowed both contraction and relaxation kinetics, increasing the twitch time to peak (143 +/- 6 vs. 100 +/- 4 ms in control, P< 0.001) and the time to half relaxation (124 +/- 6 vs. 75 +/- 6 ms in control, P< 0.001). Increased pacing frequency increased contractile force threefold in control myocardium (P< 0.001) but caused no increase of force in Ro1-expressing myocardium. When stimulation was interrupted with rests, postrest force increased in control myocardium, but there was postrest decay of force in Ro1-expressing myocardium. These results suggest that defects in contractility mediated by G(i) signaling may contribute to the development of dilated cardiomyopathy. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pharmacol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA. RP Baker, AJ (reprint author), San Francisco VA Med Ctr, Div Cardiol, 111C,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [HL-54890, HL-56257, HL-60664] NR 26 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2001 VL 280 IS 4 BP H1653 EP H1659 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 410VL UT WOS:000167461700027 PM 11247776 ER PT J AU Christopher, J Velarde, V Zhand, DA Mayfield, D Mayfield, RK Jaffa, AA AF Christopher, J Velarde, V Zhand, DA Mayfield, D Mayfield, RK Jaffa, AA TI Regulation of B-2-kinin receptors by glucose in vascular smooth muscle cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE protein kinase C; bradykinin; intracellular calcium ID PROTEIN-KINASE-C; HUMAN-ENDOTHELIAL-CELLS; DIABETIC COMPLICATIONS; MESANGIAL CELLS; ANGIOTENSIN-II; GROWTH-FACTOR; BASEMENT-MEMBRANE; GENE-EXPRESSION; FOS INDUCTION; TGF-BETA AB The development of vascular disease is accelerated in hyperglycemic states. Vascular injury plays a pivotal role in the progression of atherosclerotic vascular disease in diabetes, which is characterized by increased vascular smooth muscle cell (VSMC) proliferation and extracellular matrix accumulation. We previously reported that diabetes alters the activity of the kallikrein- kinin system and results in the upregulation of kinin receptors in the vessel wall. To determine whether glucose can directly influence the regulation of kinin receptors, the independent effect of high glucose (25 mM) on B-2-kinin receptors (B2KR) in VSMC was examined. A threefold increase in B2KR protein levels and a 40% increase in B2KR surface receptors were observed after treatment with high glucose after 24 h. The mRNA levels of B2KR were also significantly increased by high glucose as early as 4 h later. To elucidate the cellular mechanisms by which glucose regulates B2KR, we examined the role of protein kinase C (PKC). High glucose increased total PKC activity and resulted in the translocation of conventional PKC isoforms (beta (1) and beta (2)), novel (epsilon), and atypical (zeta) PKC isoforms into the membrane. Inhibition of PKC activity prevented the increase in B2KR levels induced by ambient high glucose. These findings provide the first evidence that glucose regulates the expression of beta (2) receptors in VSMC and provide a rationale to further study the interaction between glucose and kinins on the pathogenesis of atherosclerotic vascular disease in diabetes. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Cell & Mol Pharmacoll, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Expt Therapeut, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Jaffa, AA (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250776, Charleston, SC 29425 USA. FU NCRR NIH HHS [S10RR13005]; NHLBI NIH HHS [HL-07260, HL-55782]; NIDDK NIH HHS [DK-46563] NR 51 TC 27 Z9 27 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2001 VL 280 IS 4 BP H1537 EP H1546 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 410VL UT WOS:000167461700015 PM 11247764 ER PT J AU Downey, P Sapirstein, A O'Leary, E Sun, TX Brown, D Bonventre, JV AF Downey, P Sapirstein, A O'Leary, E Sun, TX Brown, D Bonventre, JV TI Renal concentrating defect in mice lacking group IV cytosolic phospholipase A(2) SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE mouse; osmolality; kidney concentrating mechanism; prostaglandin; aquaporin; eicosanoid ID GLOMERULAR MESANGIAL CELLS; CHOLERA-TOXIN INTERACTIONS; WATER CHANNEL; RAT-KIDNEY; COLLECTING TUBULE; MOUSE; PROSTAGLANDIN-E2; VASOPRESSIN; PGE2; LOCALIZATION AB Eicosanoids regulate various cellular functions that are important in physiological and pathophysiological processes. Arachidonic acid is released from membranes by phospholipase A(2) (PLA(2)) activity. Activated macrophages derived from mice lacking the 85-kDa group IV cytosolic PLA(2) (cPLA(2)) have a markedly reduced release of prostaglandin E(2) and leukotrienes B(4) and C(4). Under basal conditions and after furosemide, urinary prostaglandin E(2) excretion is reduced in cPLA(2)-knockout (cPLA(2)(-/-)) mice. Serum creatinine, Na(+), K(+), and Ca(2+) concentrations, glomerular filtration rate, and fractional excretion of Na(+) and K(+) are not different in cPLA(2)(-/-) and cPLA(2)(-/-) mice. Maximal urinary concentration is lower in 48-h water-deprived cPLA(2)(-/-) mice compared with cPLA(2)(+/+) animals (1,934 +/- 324 vs. 3,541 +/- 251 mmol/kgH(2)O). Plasma osmolality is higher (337 +/- 5 vs. 319 +/- 3 mmol/kgH(2)O) in cPLA(2)(-/-) mice that lose a greater percentage of their body weight (20 +/- 2 vs. 13 +/- 1%) compared with cPLA(2)(+/+) mice after water deprivation. Vasopressin does not correct the concentrating defect. There is progressive reduction in urinary osmolality with age in cPLA(2)(-/-) mice. Membrane-associated aquaporin-1 (AQP1) expression, identified by immunocytochemical techniques, is reduced markedly in proximal tubules of older cPLA(2)(-/-) animals but is normal in thin descending limbs. However, Western blot analysis of kidney cortical samples revealed an equivalent AQP1 signal intensity in cPLA(2)(+/+) and cPLA(2)(-/-) animals. Young cPLA(2)(-/-) mice have normal proximal tubule AQP1 staining. Collecting duct AQP2, -3, and -4 were normally expressed in the cPLA(2)(-/-) mice. Thus mice lacking cPLA(2) develop an age-related defect in renal concentration that may be related to abnormal trafficking and/or folding of AQP1 in the proximal tubule, implicating cPLA(2) in these processes. C1 Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Anesthesia Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02129 USA. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp, Med Serv, Suite 4002,149 13th St, Charlestown, MA 02129 USA. EM joseph_bonventre@hms.harvard.edu FU NIDDK NIH HHS [DK-02493, DK-38452, DK-39773]; NINDS NIH HHS [NS-10828] NR 45 TC 45 Z9 45 U1 0 U2 0 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 APR PY 2001 VL 280 IS 4 BP F607 EP F618 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 410VK UT WOS:000167461600007 PM 11249852 ER PT J AU Heilig, CW Kreisberg, JI Freytag, S Murakami, T Ebina, Y Guo, L Heilig, K Loberg, R Qu X Jin, Y Henry, D Brosius, FC AF Heilig, CW Kreisberg, JI Freytag, S Murakami, T Ebina, Y Guo, L Heilig, K Loberg, R Qu, X Jin, Y Henry, D Brosius, FC TI Antisense GLUT-1 protects mesangial cells from glucose induction of GLUT-1 and fibronectin expression SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE glucose; GLUT-1; antisense; chloramphenicol acetyltransferase assay; fibronectin ID GLYCOSYLATION END-PRODUCTS; GROWTH-FACTOR-BETA; DIABETIC NEPHROPATHY; GENE-EXPRESSION; KINASE-C; ALDOSE REDUCTASE; POLYOL PATHWAY; MESSENGER-RNA; RAT-KIDNEY; HYPERGLYCEMIA AB A stable clone of rat mesangial cells expressing antisense GLUT-1 (i.e., MCGT1AS cells) was developed to protect them from high glucose exposure. GLUT-1 protein was reduced 50%, and the 2-deoxy-[(3)H] glucose uptake rate was reduced 33% in MCGT1AS. MCLacZ control cells and MCGT1 GLUT-1-overexpressing cells were used for comparisons. In MCLacZ, 20 mM D-glucose increased GLUT-1 transcription 90% vs. no increase in MCGT1AS. Glucose (8 mM) and 12 mM xylitol [a hexose monophosphate (HMP) shunt substrate] did not stimulate GLUT-1 transcription. An 87% replacement of the standard 8 mM D-glucose with 3-O-methylglucose reduced GLUT-1 transcription 80%. D-Glucose (20 mM) increased fibronectin mRNA and protein by 47 and 100%, respectively, in MCLacZ vs. no increases in MCGT1AS. Fibronectin synthesis was elevated 48% in MCGT1 and reduced 44% in MCGT1AS. We conclude that 1) transcription of GLUT-1 in response to D-glucose depends on glucose metabolism, although not through the HMP shunt, and 2) antisense GLUT-1 treatment of mesangial cells blocks D-glucose-induced GLUT-1 and fibronectin expression, thereby demonstrating a protective effect that could be beneficial in the setting of diabetes. C1 Johns Hopkins Univ, Sch Med, Div Nephrol, Baltimore, MD 21205 USA. Univ Rochester, Med Ctr, Nephrol Unit, Rochester, NY 14642 USA. Henry Ford Hosp, Div Mol Biol, Detroit, MI 48202 USA. Univ Michigan, Dept Med, Div Nephrol, Ann Arbor, MI 48109 USA. Univ Michigan, Vet Affairs Med Ctr, Ann Arbor, MI 48109 USA. Michigan State Univ, Coll Human Med, Dept Physiol, E Lansing, MI 48824 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78284 USA. Audie L Murphy Vet Adm Hosp, San Antonio, TX 78284 USA. Univ Tokushima, Sch Med, Tokushima 770, Japan. RP Heilig, CW (reprint author), Johns Hopkins Univ, Sch Med, Div Nephrol, Ross Bldg 965 S,720 Rutland Ave, Baltimore, MD 21205 USA. EM cheilig@welch.jhu.edu FU NIDDK NIH HHS [1-K08-DK-01953, 1 RO1 DK-54507-01, K11-DK-02193] NR 36 TC 32 Z9 34 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 APR PY 2001 VL 280 IS 4 BP F657 EP F666 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 410VK UT WOS:000167461600012 PM 11249857 ER PT J AU Berg, AO Allan, JD Frame, PS Homer, CJ Lieu, TA Mulrow, CD Orleans, CT Peipert, JF Pender, NJ Sox, HC Teutsch, SM Westhoff, C Woolf, SH AF Berg, AO Allan, JD Frame, PS Homer, CJ Lieu, TA Mulrow, CD Orleans, CT Peipert, JF Pender, NJ Sox, HC Teutsch, SM Westhoff, C Woolf, SH CA US Preventive Serv Task Force TI Screening for skin cancer - Recommendations and rationale SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article C1 Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, Sch Nursing, San Antonio, TX 78284 USA. Tri Cty Family Med, Cohocton, NY USA. Univ Rochester, Rochester, NY 14627 USA. Natl Initiat Childrens Healthcare Qual, Boston, MA USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Brown Univ, Women & Infants Hosp, Providence, RI 02908 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. Merck & Co Inc, Outcomes Res & Management, W Point, PA USA. Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA. Med Coll Virginia, Dept Family Practice, Fairfax, VA USA. RP Berg, AO (reprint author), US Prevent Serv Task Force, Agcy Healthcare Res & Qual, Ctr Practice & Technol Assessment, 6010 Execut Blvd,Suite 300, Rockville, MD USA. NR 9 TC 7 Z9 7 U1 0 U2 0 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 APR PY 2001 VL 20 IS 3 SU S BP 44 EP 46 DI 10.1016/S0749-3797(01)00259-8 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 423HV UT WOS:000168170700009 ER PT J AU Pignone, MP Phillips, CJ Atkins, D Teutsch, SM Mulrow, CD Lohr, KN AF Pignone, MP Phillips, CJ Atkins, D Teutsch, SM Mulrow, CD Lohr, KN TI Screening and treating adults for lipid disorders SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE cardiovascular disease; cholesterol; coronary disease; hyperlipidemia; preventive health services; evidence-based medicine; MEDLINE; methods; lipids; mass screening; mortality; drug therapy ID CORONARY HEART-DISEASE; SERUM-CHOLESTEROL CONCENTRATION; RANDOMIZED CONTROLLED TRIALS; CARDIOVASCULAR RISK-FACTORS; EVENTS CARE TRIAL; BLOOD CHOLESTEROL; PRIMARY-PREVENTION; MYOCARDIAL-INFARCTION; HEALTH CHECKS; PRAVASTATIN AB Context: Screening and treatment of lipid disorders in people at high risk for future coronary heart disease (CHD) events has gained wide acceptance, especially for patients with known CHD, but the proper role in people with low to medium risk is controversial. Objective: To examine the evidence about the benefits and harms of screening and treatment of lipid disorders in adults without known cardiovascular disease for the U.S. Preventive Services Task Force. Data Sources: We identified English-language articles on drug therapy, diet and exercise therapy, and screening for lipid disorders from comprehensive searches of the MEDLINE database from 1994 through July 1999, We used published systematic reviews, hand searching of relevant articles, the second Guide to Clinical Preventive Services, and extensive peer review to identify important older articles and to ensure completeness. Data Synthesis: There is strong, direct evidence that drug therapy reduces CHD events, CHD mortality, and possibly total mortality in middle-aged men (35 to 65 years) with abnormal lipids and a potential risk of CHD events greater than 1% to 2% per year. Indirect evidence suggests that drug therapy is also effective in other adults with similar levels of risk. The evidence is insufficient about benefits and harms of treating men younger than 35 years and women younger than 45 years who have abnormal lipids but no other risk factors for heart disease and low risk for CHD events (less than 1% per year). Trials of diet therapy for primary prevention have led to long-term reductions in cholesterol of 3% to 6% but have not demonstrated a reduction in CHD events overall. Exercise programs that maintain or reduce body weight can produce short-term reductions in total cholesterol of 3% to 6%, but longer-term results in unselected populations have found smaller or no effect. To identify accurately people with abnormal lipids, at least two measurements: of total cholesterol and high-density lipoprotein cholesterol are required. The role of measuring triglycerides and the optimal screening interval are unclear from the available evidence. Conclusions: On the basis of the effectiveness of treatment, the availability of accurate and reliable tests, and the likelihood of identifying people with abnormal lipids and increased CHD risk, screening appears to be effective in middle-aged and older adults and in young adults with additional cardiovascular risk factors. C1 Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. AF Med Operat Agcy, Off Prevent & Hlth Serv Assessment, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, Dept Med, San Antonio, TX 78284 USA. US Dept HHS, Agcy Healthcare Res & Qual, Ctr Practice & Technol Assessment, Rockville, MD USA. Merck & Co Inc, Outcomes Res & Management, W Point, PA USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Program Hlth Outcomes, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. RP Pignone, MP (reprint author), UNC Hosp, CB 7110,5039 Old Clin Bldg, Chapel Hill, NC 27599 USA. RI H, V/M-5550-2014 FU PHS HHS [290-97-0011] NR 68 TC 46 Z9 46 U1 0 U2 1 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 APR PY 2001 VL 20 IS 3 SU S BP 77 EP 89 DI 10.1016/S0749-3797(01)00255-0 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 423HV UT WOS:000168170700014 PM 11306236 ER PT J AU Wechsler, H Lee, JE Rigotti, NA AF Wechsler, H Lee, JE Rigotti, NA TI Cigarette use by college students in smoke-free housing - Results of a national study SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE housing; primary prevention; tobacco smoke pollution; smoking; students; tobacco; universities ID ALCOHOL-USE; CONSEQUENCES; DRINKING AB Background: Cigarette-smoking rates have increased in recent years among college students. Smoke-free residences offer a possible means of reducing or preventing smoking. However, their use has as vet not been evaluated. This paper examines whether students residing in smoke-free residences are less likely to smoke cigarettes than students in other campus residences, and if such lower rates apply to all types of students and colleges. Methods: The Harvard School of Public Health College Alcohol Study surveyed a nationally representative sample of college students at 128 U.S. 4-year colleges regarding tobacco use and related behaviors in the spring of 1999. The responses of students living in smoke-free and unrestricted residences at 101 campuses were compared. Results: Current smoking prevalence was significantly lower among residents of smoke-free housing (21.0%) as compared with residents of unrestricted housing (30.6%, p<0.0001). The lower rate of current cigarette use was consistent with all types of student and college characteristics with few exceptions. Current cigarette use was significantly lower for those living in smoke-free housing than for residents of unrestricted housing among students who were not regular smokers before age 19 (10% vs 16.9%, p<0.0001), but not among students who smoked regularly before age 19. Conclusions: Smoke-free residences may help protect those students who were not regular smokers in high school from smoking in college. However, the difference in smoking rates may be due to self-selection of students into smoke-free residences. Since smoke-free options also protect students fr-om secondhand smoke and dormitory fires, colleges should provide these types of residences for all students who request them, and should also encourage others to choose them. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wechsler, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, 677 Huntington Ave, Boston, MA 02115 USA. NR 17 TC 57 Z9 57 U1 0 U2 6 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 APR PY 2001 VL 20 IS 3 BP 202 EP 207 DI 10.1016/S0749-3797(00)00313-5 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 422AK UT WOS:000168095600005 PM 11275447 ER PT J AU Spencer, TJ Biederman, J Faraone, S Mick, E Coffey, B Geller, D Kagan, J Bearman, SK Wilens, T AF Spencer, TJ Biederman, J Faraone, S Mick, E Coffey, B Geller, D Kagan, J Bearman, SK Wilens, T TI Impact of tic disorders on ADHD outcome across the life cycle: Findings from a large group of adults with and without ADHD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT-HYPERACTIVITY; DEFICIT/HYPERACTIVITY DISORDER; CHILDHOOD-ONSET; PSYCHIATRIC-DISORDERS; TOURETTES-SYNDROME; FAMILY HISTORY; DOUBLE-BLIND; CHILDREN; METHYLPHENIDATE; COMORBIDITY AB Objective: The impact of tic disorders on the outcome of attention deficit hyperactivity disorder (ADHD) remains a subject of high scientific and clinical interest. To evaluate the impact of comorbid ADHD and tic disorders from a lifespan perspective, the authors systematically examined data from adults with and without ADHD. Method: They comprehensively evaluated 312 consecutively referred adults with ADHD and 252 comparison subjects without ADHD. Tic disorders were characterized along with a wide range of neuropsychiatric correlates, including other comorbid disorders as well as indexes of function in the domains of school, cognition, and interpersonal functioning. Results: A significantly greater proportion of adults with ADHD (12%) than those without ADHD (4%) had tic disorders. Tic disorders followed a mostly remitting course and had little impact on functional capacities. In addition, tic disorders were not associated with stimulant use. Conclusions: These findings in adults with ADHD confirm and extend previous findings in young subjects with ADHD, documenting that although individuals with ADHD are at greater risk for tic disorders, the presence of tic disorders has a limited impact on ADHD outcome. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, WACC 725, Psychiat Serv, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, WACC 725, Psychiat Serv, 15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-57511] NR 39 TC 38 Z9 38 U1 3 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2001 VL 158 IS 4 BP 611 EP 617 DI 10.1176/appi.ajp.158.4.611 PG 7 WC Psychiatry SC Psychiatry GA 419CN UT WOS:000167931900015 PM 11282697 ER PT J AU Allen, JD Stoddard, AM Sorensen, G AF Allen, JD Stoddard, AM Sorensen, G TI Promoting breast and cervical cancer screening at the workplace: Results from the Woman to Woman Study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID WORKSITE HEALTH PROMOTION; MAMMOGRAPHY UTILIZATION; INCREASE MAMMOGRAPHY; ETHNIC-GROUPS; WOMEN; INTERVENTION; PHYSICIANS; OUTCOMES; PROGRAM; IMPACT AB Objectives. This article reports findings from a peer-delivered intervention designed to increase use of breast and cervical cancer screening. Methods. Twenty-six worksites were randomly assigned to the intervention or comparison group. The 16-month intervention consisted of group discussions, outreach, and educational campaigns. Data were collected from a random sample of women employees stratified by age (baseline n=2943; final n=2747). Cross-sectional analyses were conducted to evaluate the impact of the intervention on screening behaviors. Results. Relative to comparison worksites, the intervention group experienced greater increases in the percentage of women who reported a recent mammogram (7.2% vs 5.6%), clinical breast examination (5.8% vs 2.1%), and Papanicolaou (Pap) test (4.7% vs 1.9%). After worksite cluster and age strata were controlled for, the observed increase in Pap tests was significantly greater in the intervention group (odds ratio [OR] = 1.28; 95% confidence interval [CI] = 1.01, 1.62); however, differences in mammography screening rates (OR = 1.14; 95% CI = 0.90, 1.44) and clinical breast examination (OR = 1.19; 95% CI = 0.96,1.49) were not statistically significant. Conclusions. Intervention activities produced a modest increase in cervical cancer screening, but they did not accelerate breast cancer screening rates above the observed secular trend. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth, Amherst, MA 01003 USA. SEIU, Massachusetts State Council, Boston, MA USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. RI Allen, Jennifer/M-2113-2015 FU NCI NIH HHS [R01 CA 66038] NR 44 TC 32 Z9 32 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2001 VL 91 IS 4 BP 584 EP 590 DI 10.2105/AJPH.91.4.584 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BM UT WOS:000170345100010 PM 11291370 ER PT J AU Tobin, MJ Jubran, A Laghi, F AF Tobin, MJ Jubran, A Laghi, F TI Patient-ventilator interaction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID VARYING INSPIRATORY FLOW; PRESSURE SUPPORT VENTILATION; MECHANICAL VENTILATION; RESPIRATORY OUTPUT; BREATHING EFFORT; PULMONARY; FREQUENCY; DURATION; VOLUME; HUMANS AB One of the most frequent reasons for instituting mechanical ventilation is to decrease a patient's work of breathing. To achieve this goal, neuromuscular blockade was initially used to eliminate a patient's respiratory efforts, resulting in controlled ventilation. Neuromuscular blocking agents, however, predispose to numerous hazards, and, today, some means of assisted ventilation is usually employed. Surprisingly, we do not know the ideal level of respiratory muscle unloading during mechanical ventilation. To consider this issue, we need a means of measuring a patient's respiratory effort. Inspiratory pressure-time product (PTP), which quantifies swings in intrathoracic pressure, is closely related to oxygen cost of breathing and has several advantages over measurements of mechanical work of breathing (1), In 17 patients failing a trial of weaning from mechanical ventilation, their average PTP was 388 cm H2O . s/min (2); the average value in healthy subjects is 94 cm H2O . s/min. With carefully selected settings, a patient's inspiratory PTP can be reduced into the normal range with assisted ventilation (3). For the most effective unloading of the inspiratory muscles, the ventilator should cycle in synchrony with the activity of a patient's own respiratory rhythm. The interplay between these two pumps is complex, and problems can arise at several points in the respiratory cycle: the onset of ventilator triggering, the rest of inspiration after triggering, the switch from inspiration to expiration, and the end of expiration. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Hines, IL USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 35 TC 120 Z9 127 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 2001 VL 163 IS 5 BP 1059 EP 1063 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 426QJ UT WOS:000168359600010 PM 11316635 ER PT J AU Cooper, JAD Ridgeway, AL Pearson, J Culbreth, RR AF Cooper, JAD Ridgeway, AL Pearson, J Culbreth, RR TI Attenuation of interleukin 8-induced nasal inflammation by an inhibitor peptide SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID SEASONAL ALLERGIC RHINITIS; INFLUENZA-A NUCLEOPROTEIN; NEUTROPHIL APOPTOSIS; BRONCHIAL LAVAGE; CHEMOKINES; VIRUS; EXPRESSION; INTEGRINS; BETA(2) AB Polymorphonuclear neutrophils (PMNs) infiltrate tissue in response to chemoattractants, including interleukin 8 (IL-8), Infiltrating PMNs clear microorganisms but also cause tissue damage. We previously reported the presence in human bronchial ravage of a peptide that inhibits PMN functions. The current project assessed (1) effects of a synthetic analog of this peptide (synthetic neutrophil inhibitor peptide, SNIP) on IL-8-induced nasal inflammation in humans, (2) effects of SNIP on PMN apoptosis and chemotaxis, (3) specific binding of SNIP to PMNs, and (4) evidence of larger molecules with the SNIP sequence. Results show that SNIP attenuates IL-8-induced nasal inflammation, inhibits in vitro PMN chemotaxis to IL-8, and accentuates PMNs apoptosis, PMNs contain specific SNIP-binding sites and the integrin CR3 (CD11b/CD18), or a CR3-associated molecule, is one SNIP-binding molecule. Chemotaxis to IL-8 is most potently inhibited by SNIP in the presence of fibrinogen, a CR3 ligand. Antiserum against the SNIP sequence recognizes a 70-kDa protein in bronchoalveolar lavage and an anti-SNIP immunoaffinity column binds a 70-kDa protein in U937 cell culture supernatant. U937 cell mRNA contains a 1.8-kb transcript detected with degenerate oligonucleotides designed from the SNIP sequence. These studies demonstrate that a synthetic inhibitor peptide can attenuate in vivo nasal inflammation through downregulatory effects on PMNs. C1 Univ Alabama, Div Pulm Allergy & Crit Care Med, Pulm Sect, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Pulm Sect, Birmingham, AL USA. RP Cooper, JAD (reprint author), Univ Alabama, Div Pulm Allergy & Crit Care Med, Pulm Sect, Univ Stn, Birmingham, AL 35294 USA. NR 33 TC 11 Z9 11 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 2001 VL 163 IS 5 BP 1198 EP 1205 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 426QJ UT WOS:000168359600034 PM 11316659 ER PT J AU Kobayashi, H Hataishi, R Mitsufuji, H Tanaka, M Jacobson, M Tomita, T Zapol, WM Jones, RC AF Kobayashi, H Hataishi, R Mitsufuji, H Tanaka, M Jacobson, M Tomita, T Zapol, WM Jones, RC TI Antiinflammatory properties of inducible nitric oxide synthase in acute hyperoxic lung injury SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID OXYGEN-TOXICITY; TYROSINE NITRATION; RAT LUNG; PULMONARY-HYPERTENSION; ALVEOLAR MACROPHAGES; MESSENGER-RNA; PROTECTS RATS; MICE; EXPRESSION; PEROXYNITRITE AB The objective of this study was to determine whether endogenous nitric oxide (NO), specifically the inducible NO synthase isoform (iNOS: NOS II), reduces or amplifies lung injury in mice breathing at a high oxygen tension. Previous studies have shown that exogenous (inhaled) NO protects against hyperoxia-induced lung injury, and that endogenous NO derived from iNOS inhibits leukocyte recruitment and protects against lung injury induced by lipopolysaccharide. In the present study, hyperoxia (> 98% O-2 for 72 h) induced acute lung injury in both wild-type and iNOS-deficient mice as determined by elevated albumin and lactate dehydrogenase levels in bronchoalveolar lavage fluid (BALF) and by increased extravascular lung water. Lung injury was greater in iNOS-deficient mice than in wild-type mice and was associated with an increased number of polymorphonuclear leukocytes in BALF. iNOS messenger RNA expression levels increased in the lungs of wild-type hyperoxic mice. Nitrotyrosine, a marker of reactive NO species, was expressed in both wild-type and iNOS-deficient mice in hyperoxia, indicating an iNOS-independent pathway for protein nitration, We conclude that iNOS is capable of reducing pulmonary leukocyte accumulation and lung injury. The data indicate that iNOS induction serves as a protective mechanism to minimize the effects of acute exposure to hyperoxia. C1 Kitasato Univ, Sch Med, Dept Med, Sagamihara, Kanagawa 2288555, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. RP Kobayashi, H (reprint author), Kitasato Univ, Sch Med, Dept Med, Kitasato 1-15-1 Sagamihara, Sagamihara, Kanagawa 2288555, Japan. FU NHLBI NIH HHS [HL42397] NR 43 TC 60 Z9 61 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 2001 VL 24 IS 4 BP 390 EP 397 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 427PL UT WOS:000168414700005 PM 11306431 ER PT J AU Yantiss, RK Clement, PB Young, RH AF Yantiss, RK Clement, PB Young, RH TI Endometriosis of the intestinal tract - A study of 44 cases of a disease that may cause diverse challenges in clinical and pathologic evaluation SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometriosis; intestinal tract; colitis; enteritis; inflammatory bowel disease ID SMALL BOWEL OBSTRUCTION; GASTROINTESTINAL ENDOMETRIOSIS; APPENDIX; PERFORATION; SECONDARY; NEOPLASM; COLITIS; COLON AB Endometriosis of the intestinal tract may mimic a number of diseases both clinically and pathologically. The authors evaluated 44 cases of intestinal endometriosis in which endometriosis was the primary pathologic diagnosis, and evaluated them for a variety of gross and histologic changes. Cases with pre neoplastic or neoplastic changes were excluded specifically because they were the subject of a previous study. The patients ranged in age from 28 to 56 years (mean age, 44 years), and presenting complaints included abdominal pain (n = 15), an abdominal mass (n = 12), obstruction (n = 8), rectal bleeding (n = 2), infertility (n = 3), diarrhea (n = 2), and increasing urinary frequency (n = 1). The clinical differential diagnoses included diverticulitis, appendicitis, Crohn's disease, tuboovarian abscess, irritable bowel syndrome, carcinoma, and lymphoma. Forty-two patients underwent resection of the diseased intestine and two patients underwent endoscopic biopsies. In 13 patients there were predominantly mural masses, which were multiple in two patients (mean sizer 2.6 cm), In addition, 11 cases had luminal stenosis or strictures, six had mucosal polyps, four had submucosal masses that ulcerated the mucosa (sometimes simulating carcinoma), three had serosal adhesions, one had deep fissures in the mucosa, and one was associated with appendiceal intussusception. Involvement of the lamina propria or submucosa was identified in 29 cases (66%) and, of these, 19 had features of chronic injury including architectural distortion (n = 19), dense lymphoplasmacytic infiltrates (n = 7), pyloric metaplasia of the ileum (n = 1), and fissures (n = 1), Three eases hall features of mucosal prolapse (7%), ischemic changes were seen in four (9%), and segmental acute colitis and ulceration were seen in four and six cases (9% and 13%) respectively. In 14 patients, endometriosis formed irregular congeries of glands involving the intestinal surface epithelium, mimicking adenomatous changes. Mural changes included marked concentric smooth muscle hyperplasia and hypertrophy, neuronal hypertrophy and hyperplasia, and fibrosis of the muscularis propria with serositis. Follow-up of 20 patients (range, 1-30 years; mean, 7.8 years) revealed that only two patients had recurrent symptoms. None of the patients developed inflammatory bowel disease. Endometriosis can involve the intestinal tract extensively, causing a variety of clinical symptoms, and can result in a spectrum of mucosal alterations. Because the endometriotic foci may be inaccessible to endoscopic biopsy or may not be sampled because of their focality, clinicians and pathologists should be aware of the potential of this condition to mimic other intestinal diseases. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ British Columbia, Dept Pathol, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 42 TC 123 Z9 131 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2001 VL 25 IS 4 BP 445 EP 454 DI 10.1097/00000478-200104000-00003 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 415GC UT WOS:000167711700003 PM 11257618 ER PT J AU van Roggen, JFG McMenamin, ME Belchis, DA Nielsen, GP Rosenberg, AE Fletcher, CDM AF van Roggen, JFG McMenamin, ME Belchis, DA Nielsen, GP Rosenberg, AE Fletcher, CDM TI Reticular perineurioma - A distinctive variant of soft tissue perineurioma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE peripheral nerve; soft tissue; perineurioma; tumor ID EXTRASKELETAL MYXOID CHONDROSARCOMA; EPITHELIAL MEMBRANE ANTIGEN; NERVE SHEATH TUMORS; PERIPHERAL-NERVE; CLINICOPATHOLOGICAL ANALYSIS; CELL TUMOR; NF2 GENE; CHROMOSOME-22; MENINGIOMAS; MYOEPITHELIOMAS AB Sort tissue perineurioma is a relatively recently characterized, uncommon tumor composed of perineurial cells exhibiting immunoreactivity for epithelial membrane antigen (EMA). These lesions occur preferentially in adults and may arise in a wide variety of anatomic sites. We report the clinicopathologic, immunohistochemical, and ultrastructural features of six cases of a poorly recognized morphologic variant of soft tissue perineurioma, characterized by a highly distinctive reticular growth pattern. Four of the patients were women, two were men (age range, 34-61 yrs; median, 43 yrs). Four of the cases arose in the subcutis of the upper extremity; three were located distally (thumb, finger, palm), whereas one was situated more proximally near the elbow region, One case each was located in the gingiva and subcutaneous tissue of the inguinal region, respectively. In those cases in which clinical information was available (n = 5), the lesions were asymptomatic and had been present from 4 months to 10 years before resection. Tumor size ranged from 1.5 cm to 10 cm (median size, 4.25 cm). Microscopically the lesions demonstrated a predominantly lace-like or reticular growth pattern composed of anastomosing cords of fusiform cells with bipolar cytoplasmic processes and palely eosinophilic cytoplasm. Nuclei were centrally placed, ovoid to fusiform in shape, and no mitoses were seen. Transition to more cellular areas was focally present in all cases. The stroma was variably collagenous to myxoid. Immunohistochemically all six cases stained positively for EMA but not for S-100 protein. Two cases demonstrated focal positive cytoplasmic staining for cytokeratin, whereas one case was focally desmin positive, Ultrastructural examination of two tumors showed typical features of perineurial cells. Follow up (available in only two cases) showed no evidence of recurrence. Reticular perineurioma of soft tissue represents an unusual morphologic variant within the perineurioma group, which should be distinguished from myoepithelial tumors, extraskeletal myxoid chondrosarcoma, and myxoid synovial sarcoma. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Milton S Hershey Med Ctr, Dept Pathol, Hershey, PA USA. RP Fletcher, CDM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 39 TC 70 Z9 74 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2001 VL 25 IS 4 BP 485 EP 493 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 415GC UT WOS:000167711700008 ER PT J AU Kothari, RU Hacke, W Brott, T Dykstra, EH Furlan, A Koroshetz, W Marler, J Sayre, MR AF Kothari, RU Hacke, W Brott, T Dykstra, EH Furlan, A Koroshetz, W Marler, J Sayre, MR TI Stroke SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ACUTE ISCHEMIC STROKE; THROMBOLYTIC THERAPY; PLASMINOGEN-ACTIVATOR; CONTROLLED TRIAL; PERFUSION; ALTEPLASE; EMERGENCY; ACCURACY; ECASS; SCALE C1 Borges Hosp, Borges Res Inst, Kalamazoo, MI 49001 USA. Univ Heidelberg, Heidelberg, Germany. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. PECEMMS Fdn, Apeldoom, Netherlands. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH USA. RP Kothari, RU (reprint author), Borges Hosp, Borges Res Inst, 1521 Gull Rd, Kalamazoo, MI 49001 USA. RI Sayre, Michael/E-8383-2017 OI Sayre, Michael/0000-0003-0322-3181 NR 27 TC 9 Z9 9 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2001 VL 37 IS 4 SU S BP S137 EP S144 DI 10.1067/mem.2001.114171 PG 8 WC Emergency Medicine SC Emergency Medicine GA 425ED UT WOS:000168274600015 PM 11290977 ER PT J AU Mangi, AA Dzau, VJ AF Mangi, AA Dzau, VJ TI Gene therapy for human bypass grafts SO ANNALS OF MEDICINE LA English DT Editorial Material DE E2F decoy oligonucleotide; gene therapy; neointimal hyperplasia; pressure-mediated delivery ID MUSCLE CELL-PROLIFERATION; NEOINTIMA FORMATION; IN-VIVO; EXPRESSION; ANGIOPLASTY; HYPERPLASIA; INJURY; MODEL; DECOY; VEIN AB Autologous saphenous vein is the conduit of choice for the bypass of arterial occlusive disease, be it in the peripheral arterial tree or in the coronary system. This technique is limited by primary graft failure rates approaching 20% in the first year for peripheral arterial disease and 50% at 10 years for coronary artery bypass grafting. The PREVENT trial describes a novel, safe and effective means of ex vivo transfection of harvested vein grafts with an E2F decoy oligonucleotide, with 70-74% decreases in the level of proliferating cell nuclear antigen (PCNA) and c-myc mRNA expressed by the smooth muscle cells in the vein. This translated into a statistically significant reduction in primary graft failure when used to bypass peripheral arterial occlusions in a high-risk human patient population. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Dzau, VJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 18 Z9 18 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PD APR PY 2001 VL 33 IS 3 BP 153 EP 155 DI 10.3109/07853890109002071 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 431BH UT WOS:000168611700001 PM 11370767 ER PT J AU Fernandez, M Raskind, W Wolff, J Matsushita, M Yuen, E Graf, W Lipe, H Bird, T AF Fernandez, M Raskind, W Wolff, J Matsushita, M Yuen, E Graf, W Lipe, H Bird, T TI Familial dyskinesia and facial myokymia (FDFM): A novel movement disorder SO ANNALS OF NEUROLOGY LA English DT Article ID POTASSIUM CHANNEL GENE; PAROXYSMAL DYSTONIC CHOREOATHETOSIS; BENIGN HEREDITARY CHOREA; MAPS; LINKAGE; MUTATIONS; EXPANSION; KCNA1 AB We describe here familial dyskinesia and facial myokymia (FDFM), a novel autosomal dominant disorder characterized by adventitious movements that sometimes appear choreiform and that are associated with perioral and periorbital myokymia. We report a 5-generation family with 18 affected members (10 males and 8 females) with FDFM. The disorder has an early childhood or adolescent onset. The involuntary movements are paroxysmal at early ages, increase in frequency and severity, and may become constant in the third decade. Thereafter, there is no further deterioration, and there may even be improvement in old age. The adventitious movements are worsened by anxiety but not by voluntary movement, startle, caffeine, or alcohol. The disease is socially disabling, but there is no intellectual impairment or decrease in lifespan. A candidate gene and haplotype analysis was performed in 9 affected and 3 unaffected members from 3 generations of this family using primers for polymorphic loci closely flanking or within genes of interest. We excluded linkage to II regions containing genes associated with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral-pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease locus on Ip that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage-gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea-acanthocytosis locus on 9q21; 7) the Huntington-like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2-q11,2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and the CACNA1A gene, a brain-specific P/Q-type calcium channel gene associated with ataxia and hemiplegic migraine. Our results provide further evidence of genetic heterogeneity in autosomal dominant movement disorders and suggest that a novel gene underlies this new condition. C1 Univ Washington, Sch Med, Vet Affairs Med Ctr, Dept Med,Geriatr Res Serv,GRECC S182, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98108 USA. Childrens Hosp, Med Ctr, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Serv, Seattle, WA USA. RP Bird, T (reprint author), Univ Washington, Sch Med, Vet Affairs Med Ctr, Dept Med,Geriatr Res Serv,GRECC S182, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [1 T32 AG00258-01A1] NR 25 TC 19 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2001 VL 49 IS 4 BP 486 EP 492 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 418FJ UT WOS:000167880000010 PM 11310626 ER PT J AU Golden, D Zeitels, SM Hillman, RE Jarboe, J Bunting, G Spanou, K AF Golden, D Zeitels, SM Hillman, RE Jarboe, J Bunting, G Spanou, K TI Stroboscopic assessment of vocal fold keratosis and glottic cancer SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY MAY 15-16, 2000 CL ORLANDO, FLORIDA SP Amer Broncho Esophagol Assoc DE cancer; carcinoma; dysphonia; dysplasia; hoarseness; keratosis; laryngoscopy; leukoplakia; microflap; microlaryngoscopy; phonomicrosurgery; phonosurgery; stroboscopy; vocal cord; vocal fold AB Disruption of the normal viscoelastic properties of the superficial lamina propria (SLP) results in aberrant vocal fold vibration and mucosal wave propagation. Therefore, an investigation was performed to determine whether stroboscopy is a reliable method for 1) differentiating invasive glottic carcinoma from intraepithelial atypia or 2) determining the depth of cancer invasion. An analysis was done on the preoperative vocal fold vibration characteristics of 62 keratotic (intraepithelial, 45; cancer, 17) lesions that were subsequently resected by means of microlaryngoscopy. Histopathology and intraoperative mapping were used to specify the depth of invasion. A panel of 4 blinded judges was used to assess the amplitude of vocal fold vibration and the magnitude of mucosal wave activity in the region of the lesion from videostroboscopic recordings. The final comparative data set comprised only those ratings that achieved at least 75% interjudge agreement. Of the 28 intraepithelial lesions that could be reliably evaluated for amplitude of vocal fold vibration, only 2 were normal, with the amplitude reduced in 24 and absent in 2. Of the 30 intraepithelial lesions in which mucosal wave activity could be reliably assessed, only 2 were normal. with the wave reduced in 24 and absent in 4. Furthermore, amplitude of vocal fold vibration and magnitude of mucosal wave propagation were absent in 2 of 4 carcinomas in which the depth of microinvasion did not reach the vocal ligament. According to the findings herein, reduced amplitude of vocal fold vibration and/or mucosal wave propagation associated with keratosis did not reliably predict the presence of cancer or the depth of cancer invasion into the laminae propriae. However, the presence of a flexible mucosal wave probably indicates that there is not extensive vocal ligament invasion. Reductions in the amplitude of vocal fold vibration and in mucosal wave magnitude were usually noted in intraepithelial atypia. despite the fact that there was no invasion into the SLP. The reduced epithelial pliability could be due to bulky keratosis and/or alteration of the SLP occurring as a result of inflammation or fibrovascular scarring. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 20 TC 1 Z9 1 U1 1 U2 4 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 APR PY 2001 VL 110 IS 4 BP 293 EP 298 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 420QD UT WOS:000168014900001 ER PT J AU Lehtinen, JT Belt, EA Kauppi, MJ Kaarela, K Kuusela, PP Kautiainen, HJ Lehto, MUK AF Lehtinen, JT Belt, EA Kauppi, MJ Kaarela, K Kuusela, PP Kautiainen, HJ Lehto, MUK TI Bone destruction, upward migration, and medialisation of rheumatoid shoulder: a 15 year follow up study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID ARTHRITIS; SURGERY AB Objective-To evaluate bone destruction, upward migration, and medialisation of the glenohumeral (GH) joint in a cohort of 74 patients with seropositive and erosive rheumatoid arthritis followed up prospectively. Methods-At the 15 year follow up 148 shoulders were radiographed by a standard method. Bone destruction in the GH joint was examined from the radiographs by four methods, of which three measured the migration and one the remodelling of the humeral head. The distances from the greater tuberosity of the humeral head to the coracoid process (medialisation distance (MD)) and to the articular surface of the humeral head (GA) have been previously developed to evaluate the preoperative offsets of the arthritic GH joint. Medial displacement index (MI) and upward migration index (UI) have been recently developed to evaluate the destructive pattern of the rheumatoid GH joint. Destruction of the GH joints was assessed by the Larsen method on a scale of 0 to 5. The relation between the measurements and the grade of destruction of the GH joints was examined. UI was compared with our previous measurements of the subacromial space. Results-Both the MI and the UI had a negative correlation with the GH joint destruction (Larsen grade), r=-0.49 (95% CI -0.36 to -0.60) and r=-0.58 (95% CI -0.46 to -0.68). The UI correlated significantly with the subacromial space, r=0.90 (95% CI 0.86 to 0.93). The mean MI and UI measurements of the non-affected joints were within the reported normal variation. The mean MD collapsed between Larsen grades 4 (83.0 mm) and 5 (65.5 mm). The morphology of the humeral head began to flatten and erode from the grade 3 onwards and medial head destruction was detected at grade 5. Conclusions-Medialisation seems to be preceded by upward migration of the humeral head, indicating rotator cuff damage. Symptomatic Larsen grade 3 shoulders should be intensively followed up by clinical and radiological means. Ifa total shoulder arthroplasty is considered, an orthopaedic consultation is worthwhile at a sufficiently early stage (Larsen 3 and 4), when soft tissue structures responsible for function are still in proper condition and timing of the operative procedure can be well planned. C1 Rheumatism Fdn Hosp, Dept Orthopaed, FIN-18120 Heinola, Finland. Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Boston, MA USA. Tampere Univ Hosp, Tampere, Finland. RP Belt, EA (reprint author), Rheumatism Fdn Hosp, Dept Orthopaed, FIN-18120 Heinola, Finland. NR 28 TC 19 Z9 20 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD APR PY 2001 VL 60 IS 4 BP 322 EP 326 DI 10.1136/ard.60.4.322 PG 5 WC Rheumatology SC Rheumatology GA 411KF UT WOS:000167498700004 PM 11247859 ER PT J AU Sanford, LD Silvestri, AJ Ross, RJ Morrison, AR AF Sanford, LD Silvestri, AJ Ross, RJ Morrison, AR TI Influence of fear conditioning on elicited ponto-geniculo-occipital waves and rapid eye movement sleep SO ARCHIVES ITALIENNES DE BIOLOGIE LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; ELECTRICAL-STIMULATION; PONTOGENICULOOCCIPITAL WAVES; CENTRAL NUCLEUS; IMMOBILIZATION STRESS; CANINE NARCOLEPSY; ACOUSTIC STARTLE; LOCUS-COERULEUS; PGO SPIKES; ALBINO-RAT C1 Univ Penn, Sch Vet Med, Dept Anim Biol, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Sanford, LD (reprint author), Univ Penn, Sch Vet Med, Dept Anim Biol, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [MH42903]; NINDS NIH HHS [NS35281] NR 67 TC 53 Z9 54 U1 0 U2 3 PU UNIV PISA PI PISA PA LUNGARNO A PACINOTTI 43, 56100 PISA, ITALY SN 0003-9829 J9 ARCH ITAL BIOL JI Arch. Ital. Biol. PD APR PY 2001 VL 139 IS 3 BP 169 EP 183 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 421ZQ UT WOS:000168093800001 PM 11330199 ER PT J AU George, MS Anton, RF Bloomer, C Teneback, C Drobes, DJ Lorberbaum, JP Nahas, Z Vincent, DJ AF George, MS Anton, RF Bloomer, C Teneback, C Drobes, DJ Lorberbaum, JP Nahas, Z Vincent, DJ TI Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID COMPULSIVE DRINKING SCALE; COCAINE; RAT AB Background: Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. Methods: Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving, before and after. a sip of alcohol, and after a g-minute randomized pl presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blued oxygen level-dependent technique. Results: Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. Conclusions: When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior. C1 Ralph H Johnson Vet Hosp, Charleston, SC USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. FU NIAAA NIH HHS [AA10761-03] NR 27 TC 223 Z9 231 U1 3 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2001 VL 58 IS 4 BP 345 EP 352 DI 10.1001/archpsyc.58.4.345 PG 8 WC Psychiatry SC Psychiatry GA 419ZF UT WOS:000167978900005 PM 11296095 ER PT J AU Dugas, JE Zurek, L Paster, BJ Keddie, BA Leadbetter, ER AF Dugas, JE Zurek, L Paster, BJ Keddie, BA Leadbetter, ER TI Isolation and characterization of a Chryseobacterium strain from the gut of the American cockroach, Periplaneta americana SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE flavobacteria; Chryseobacterium; flexirubin; fumarate respiration; gut; American cockroach ID FLAVOBACTERIUM-GLEUM; CLASSIFICATION; METHANOGENS; BACTERIA; FLORA AB 16S rDNA sequence cloned directly from whole-gut microbiota of the American cockroach, Periplaneta americana, indicated the presence of a member of the Bacteroides/Flavobacterium group most closely related to the genus Flavobacterium. In an attempt to confirm this finding, we isolated a yellow-pigmented bacterium (strain FR2) from the hindgut of this insect. Strain FR2 was phylogentically and phenotypically most similar to species of Flavobacterium and related bacteria, namely Chryseobacterium indologenes. Fifty-four other yellow-pigmented bacteria isolated during a 1-year study shared the salient phenotypic characteristics of Chryseobacterium spp., and thus were considered the same phenotype. This phenotype's abundance was related to the fiber content of the insect diet, being consistently detected only in cockroaches fed a high-fiber diet (30% crude fiber by weight). The highest population density was in the hindgut, ranging from 2x10(6) to 1.2x10(7) colony forming units ml(-1) during a 1-year period. The nature of the symbiosis between the FR2 phenotype and P. americana is discussed. C1 Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada. Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. Forsyth Inst, Boston, MA 02115 USA. RP Dugas, JE (reprint author), Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. RI Keddie, Andrew/A-2654-2014 OI Keddie, Andrew/0000-0002-0131-4306 NR 22 TC 19 Z9 21 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD APR PY 2001 VL 175 IS 4 BP 259 EP 262 DI 10.1007/s002030000243 PG 4 WC Microbiology SC Microbiology GA 429MJ UT WOS:000168520700003 PM 11382221 ER PT J AU Nouri, M Terada, H Alfonso, EC Foster, CS Durand, ML Dohlman, CH AF Nouri, M Terada, H Alfonso, EC Foster, CS Durand, ML Dohlman, CH TI Endophthalmitis after keratoprosthesis - Incidence, bacterial causes, and risk factors SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Objectives: To determine the rate of endophthalmitis in a group of patients with keratoprostheses and to analyze possible risk factors. Methods: A total of 108 patient eyes, operated on between 1990 and 2000 with double-plated keratoprostheses, were analyzed with regard to the surface flora, the incidence and cause of bacterial endophthalmitis or sterile vitreitis, the keratoprosthesis design, prophylactic antibiotics, concomitant immunosuppression, and preoperative diagnosis. Results: Surveillance cultures were obtained from 30 uninfected eyes. The flora was similar to that reported in the normal population and did not vary significantly with time. Thirteen cases of bacterial endophthalmitis occurred 2 to 46 months postoperatively in the patient population that had been followed up for 2 months to 17 years (average, 3 years 4 months). The incidence was 39%;, in 13 patients with Stevens-Johnson syndrome, 19% in 27 patients with ocular cicatricial pemphigoid, and 7% in 28 patients with ocular burns. Only 1 of the other 40 cases (consisting mostly of repeated graft failures in noncicatrizing conditions) developed endophthalmitis; this patient had st filtering bleb. All endophthalmitis pathogens were gram positive: Streptococcus pneumoniae, 23%; other streptococci, 39%; Staphylococcus aureus, 23%; and Staphylococcus; epidermidis, 15%. Conclusions: The most important risk factor for endophthalmitis after these keratoprostheses was found to be preoperative diagnosis. The rate of infection was very high in Stevens-Johnson syndrome and ocular cicatricial pemphigoid, moderate in chemical burns, and low in noncicatrizing corneal disease. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalnol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalnol, Boston, MA 02115 USA. Univ Miami, Sch Med, Miami, FL 33152 USA. Bascom Palmer Eye Inst, Miami, FL 33136 USA. RP Dohlman, CH (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalnol, 243 Charles St, Boston, MA 02114 USA. NR 8 TC 114 Z9 120 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2001 VL 119 IS 4 BP 484 EP 489 PG 6 WC Ophthalmology SC Ophthalmology GA 422QL UT WOS:000168130700001 PM 11296013 ER PT J AU Uy, HS Nguyen, QD Arbour, J Gravel, M D'Amico, DJ Jakobiec, FA Foster, CS AF Uy, HS Nguyen, QD Arbour, J Gravel, M D'Amico, DJ Jakobiec, FA Foster, CS TI Sclerosing inflammatory pseudotumor of the eye SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ORBITAL PSEUDOTUMOR; LYMPHOID NEOPLASIA AB We report the clinical course and pathologic findings in a case of intraocular sclerosing inflammatory pseudotumor in a 21-year-old man. The patient initially had a unilateral right interstitial keratitis, scleritis, uveitis, ciliary body mass, and retinal detachment. Scleral and vitreous biopsy specimens revealed an inflammatory process. The eye was eventually enucleated despite therapy with high doses of prednisone and ciprofloxacin hydrochloride. Histologic examination of the globe showed nongranulomatous, acute (neutrophils) and chronic (lymphocytes and histiocytes) inflammation with proliferation of fibrous tissue within the vitreous cavity, uvea, sclera, and contiguous orbital fibroadipose tissue. The contralateral eye later developed a similar mass that resolved following aggressive and prolonged immunosuppressive therapy with retention of 20/16 visual acuity. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA 02114 USA. Hosp Sacre Coeur, Montreal, PQ, Canada. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Schepens Retina Fdn, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 15 Z9 16 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2001 VL 119 IS 4 BP 603 EP 607 PG 5 WC Ophthalmology SC Ophthalmology GA 422QL UT WOS:000168130700019 PM 11296029 ER PT J AU Pena, JA Fox, JG Ferraro, MJ Versalovic, J AF Pena, JA Fox, JG Ferraro, MJ Versalovic, J TI Molecular resistance testing of Helicobacter pylori in gastric biopsies SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID 23S RIBOSOMAL-RNA; POLYMERASE CHAIN-REACTION; CLARITHROMYCIN RESISTANCE; RAPID DETECTION; ANTIMICROBIAL RESISTANCE; ANTIBIOTIC-RESISTANCE; MACROLIDE RESISTANCE; POINT MUTATIONS; UNITED-STATES; PCR AB Objective.-To evaluate simultaneous diagnosis of infection and molecular resistance testing of Helicobacter pylori. Methods.-Gastric biopsies were obtained from 26 rapid urease-positive and 51 rapid urease-negative test kits used to diagnose H pylori infection. Following glass bead-assisted DNA isolation, amplification of H pylori 16S ribosomal DNA (rDNA), glmM, and 23S rDNA target genes was performed. Results.-Helicobacter pylori DNA was successfully amplified from 100% (26/26) of urease-positive and 3.9% (2/ 51) of urease-negative gastric biopsies. Subsequent restriction enzyme-mediated digestion of 23S rDNA amplification products revealed that 17% (4/24) of urease-positive and H pylori DNA-positive biopsy specimens contained point mutations (A2142G or A2143G) associated with clarithromycin resistance. Helicobacter pylori DNA from gastric biopsies was successfully amplified 8 weeks following rapid urease testing. Conclusion.-Helicobacter pylori genotyping may be used to detect macrolide-resistant H pylori in individuals prior to initiation of therapy or in patients refractory to anti-H pylori therapy. Two urease-negative specimens yielded Helicobacter DNA distinct from that of H pylori and indicated the need for further investigations of Helicobacter species present in the human stomach. C1 Massachusetts Gen Hosp, Mol Diagnost Lab, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Northeastern Univ, Dept Med Lab Sci, Boston, MA 02115 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Versalovic, J (reprint author), Massachusetts Gen Hosp, Mol Diagnost Lab, Dept Pathol, Div Lab Med, GRJ 529,55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI37750] NR 36 TC 7 Z9 7 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2001 VL 125 IS 4 BP 493 EP 497 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 419ZY UT WOS:000167980500006 PM 11260622 ER PT J AU Moncure, AC AF Moncure, AC TI Tenax propositi on uncharted seas SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the New-England-Surgical-Society CY OCT 07, 2000 CL BOSTON, MASSACHUSETTS SP New England Surg Soc ID RECONSTRUCTION; MANAGEMENT; AIRWAY AB I would like to express my deep appreciation to the members of the New England Surgical Society for the privilege of serving as its president during the past year. The New England surgical community is, in my opinion, the finest in the world, making this office an especially high honor. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Moncure, AC (reprint author), Massachusetts Gen Hosp, 15 Parkman St,ACC-335, Boston, MA 02114 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2001 VL 136 IS 4 BP 376 EP 382 DI 10.1001/archsurg.136.4.376 PG 7 WC Surgery SC Surgery GA 419ZH UT WOS:000167979100001 PM 11296106 ER PT J AU Pierie, JPEN Choudry, U Muzikansky, A Yeap, BY Souba, WW Ott, MJ AF Pierie, JPEN Choudry, U Muzikansky, A Yeap, BY Souba, WW Ott, MJ TI The effect of surgery and grade on outcome of gastrointestinal stromal tumors SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the New-England-Surgical-Society CY OCT 07, 2000 CL BOSTON, MASSACHUSETTS SP New England Surg Soc ID SMOOTH-MUSCLE TUMORS; PROGNOSTIC FACTORS; SURGICAL RESECTION; TRACT; LEIOMYOSARCOMAS; MYOSARCOMAS; MANAGEMENT; PATTERNS; SURVIVAL; SARCOMAS AB Hypothesis: Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-curt gastrointestinal turners. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors. Design and Setting: A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998. Patients: Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months. Main Outcome Measures: Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival. Results: Tumor distribution included 61% in the upper, 23%;, in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio=0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival. Conclusion: Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor prognosis, with decreased survival, and increased local and/or distant recurrence. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Stat Ctr, Boston, MA 02114 USA. Penn State Giesinger Hlth Syst, Dept Surg, Hershey, PA USA. RP Ott, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Surg Oncol, Cox Bldg,Room 626,100 Blossom St, Boston, MA 02114 USA. NR 24 TC 195 Z9 220 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2001 VL 136 IS 4 BP 383 EP 389 DI 10.1001/archsurg.136.4.383 PG 7 WC Surgery SC Surgery GA 419ZH UT WOS:000167979100002 PM 11296107 ER PT J AU Balcom, JH Rattner, DW Warshaw, AL Chang, Y Fernandez-del Castillo, C AF Balcom, JH Rattner, DW Warshaw, AL Chang, Y Fernandez-del Castillo, C TI Ten-year experience with 733 pancreatic resections - Changing indications, older patients, and decreasing length of hospitalization SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the New-England-Surgical-Society CY OCT 07, 2000 CL BOSTON, MASSACHUSETTS SP New England Surg Soc ID DUODENUM-PRESERVING RESECTION; CLINICAL PATHWAY; CURRENT MANAGEMENT; WHIPPLE RESECTION; PANCREATICODUODENECTOMY; MORTALITY; SURGERY; PYLORUS; IMPACT; HEAD AB Hypothesis: Experience with pancreatic resection for the last 10 years has resulted in new trends in patient characteristics and, for pancreaticoduodenectomy (PD), a decrease in the length of stay (LOS). This decrease is due ill part to the implementation of case management and clinical pathways. Design: Retrospective case series of patients undergoing pancreatic resection. Setting: A university-affiliated, tertiary care referral center. Patients: The study comprised 733 consecutive patients undergoing, pancreatic resection for benign or malignant disease at the Massachusetts General Hospital ill Boston from April 1990 to March 2000. Interventions: Of the 733 pancreatic resections, 489 were PD; 190, distal pancreatectomy; 40, total pancreatectomy; and 14, middle-segment pancreatectomy. Main Outcome Measures: Length of stay occurrence of delayed gastric emptying, pancreatic fistula, reoperation, readmission, or other complications; mortality and comparison of patients in 3 periods according to the implementation of case management (July 1995) and clinical pathways (September 1998). Results: For PD, patients in group 1 (April 1990 to June 1995) were significantly younger (mean +/- SD, 57 +/- 15 years) than those in group 2 (July 1995 to August 1998; mean +/- SD, 62 +/- 13 years) and group 3 (September 1998 to October 2000; mean +/- SD, 65 +/- 13 years)(P<.01). Over time, the proportion of PD for cystic rumors increased from 9.9%, to 20% (P=.01), and the proportion of PD for chronic pancreatitis decreased from 23% to 10% (P<.01), Use of pylorus-preserving PD decreased from 45% to 0% (P<.001). Delayed gastric emptying decreased from 17% to 6.1% (P<.01). Pancreatic fistula, reoperation, and mortality were unchanged. Length of stay for PD decreased from 16.1+/-0.6 to 9.5+/-0.4 days (mean+/-SE) (P<.001). Multivariate analysis showed that period, case volume, pylorus-preserving PD, and presence of complications are all independent predictors of LOS (P<.05 for all). For distal pancreatectomy, patients in groups 2 and 3 were older than those in group 1 (mean +/- SD, 57 +/- 14 vs 52+/-17 years) (P<.05). Resections for cystic tumors increased from 26% to 52% (P<.05), and resections for chronic pancreatitis decreased from 32% to 14% (P=.06). Median LOS decreased from 9 days to 6. For total pancreatectomy, resections for cystic tumors increased from 18% to 43%. Median LOS decreased from 14.5 days to 11. For all resections, case volume increased from 4 resections per month in 1990 to 5.8 in 1995 and 12 in 2000 (r = 0.83; P<.001). Conclusions: Older patients are increasingly being selected for pancreatic resection. This reflects an increasing frequency of operations performed for cystic tumors and fewer for chronic pancreatitis. With the exception of delayed gastric emptying, complications and mortality have remained the same or decreased slightly during the past 10 years. However, there has been a significant decrease in LOS; this is the result of implementation of case: management and clinical pathways, increasing case volume, decreasing incidence of delayed gastric emptying, and decreasing use of pylorus-preserving PD. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, WACC-336,55 Fruit St, Boston, MA 02114 USA. NR 47 TC 485 Z9 506 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2001 VL 136 IS 4 BP 391 EP 397 DI 10.1001/archsurg.136.4.391 PG 7 WC Surgery SC Surgery GA 419ZH UT WOS:000167979100004 PM 11296108 ER PT J AU Purnell, JQ Kahn, SE Schwartz, RS Brunzell, JD AF Purnell, JQ Kahn, SE Schwartz, RS Brunzell, JD TI Relationship of insulin sensitivity and ApoB levels to intra-abdominal fat in subjects with familial combined hyperlipidemia SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE obesity; insulin resistance; hyperlipidemia; visceral fat; apolipoproteins ID LIPOPROTEIN SUBCLASS PATTERNS; CORONARY-ARTERY DISEASE; APOLIPOPROTEIN-B LEVELS; MYOCARDIAL-INFARCTION; PLASMA-LIPOPROTEINS; GLUCOSE-TOLERANCE; ACID SUPPRESSION; VISCERAL OBESITY; HEART-DISEASE; MEN AB Familial combined hyperlipidemia (FCHL) is one of the most common familial dyslipidemias associated with premature heart disease. Subjects with FCHL typically have elevated apolipoprotein B (apoB) levels, variable elevations in cholesterol and/or triglycerides, and a predominance of small, dense, low density lipoprotein particles. It is thought that insulin resistance is important in the expression of the combined hyperlipidemia phenotype. To further characterize the relationship between insulin resistance and increased apoB levels, 11 subjects from well-characterized FCHL families and normal control subjects matched for weight and/or age underwent measurement of intra-abdominal Fat (IAF) and subcutaneous fat (SQF) by CT scan, insulin sensitivity (Si) by the frequently sampled intravenous glucose tolerance test, and lipoprotein levels. Body mass index and IAF were higher and Si was lower (more insulin resistant) in the FCHL group than in the age-matched group, but the values were similar in the FCHL group and the age- and weight-matched control group. When the relationship between body fat distribution and Si was tested with multiple linear regression, only IAF was significantly correlated with Si after the addition of SQF and body mass index as independent variables. For any level of insulin sensitivity or IAF, however, apoB levels remained higher in the FCHL subjects than in the control groups. In conclusion, in FCHL, visceral obesity is an important determinant of insulin resistance. Visceral obesity and insulin resistance, however, do not fully account for the elevated levels of apoB in this disorder, and this study provides physiological support for separate, but additive, genetic determinants in the etiology of the lipid phenotype. C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Colorado, Dept Gerontol & Geriatr Med, Denver, CO 80202 USA. RP Brunzell, JD (reprint author), Oregon Hlth Sci Univ, Div Endocrinol Diabet & Clin Nutr, Mailbox L607,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [M01-RR-00037]; NHLBI NIH HHS [P0-1 HL-30086]; NIA NIH HHS [R01 AG-08673]; NIDDK NIH HHS [5P30 DK-35816, DK-17047, K-24-DK-02654, P0-1 DK-02456] NR 50 TC 44 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2001 VL 21 IS 4 BP 567 EP 572 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 424WZ UT WOS:000168258100018 PM 11304474 ER PT J AU Zvolensky, MJ McNeil, DW Porter, CA Stewart, SH AF Zvolensky, MJ McNeil, DW Porter, CA Stewart, SH TI Assessment of anxiety sensitivity in young American Indians and Alaska Natives SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE anxiety; fear; accuturation; Native American ID GENDER-ROLE STRESS; PANIC ATTACKS; HIERARCHICAL STRUCTURE; DISORDER; WOMEN; PATHOGENESIS; PERSONALITY; PSYCHOLOGY; DIMENSIONS; PREVALENCE AB In the present study, the Anxiety Sensitivity Index [ASI; Behav. Res. Ther. 24 (1986) 1] was administered to 282 American Indian and Alaska Native college students in a preliminary effort to: (a) evaluate the factor structure and internal consistency of the ASI in a sample of Native Americans; (b) examine whether this group would report greater levels of anxiety sensitivity and gender and age-matched college students from the majority (Caucasian) culture lesser such levels; and (c) explore whether gender differences in anxiety sensitivity dimensions varied by cultural group (Native American vs. Caucasian). Consistent with existing research, results of this investigation indicated that, among Native peoples, the ASI and its subscales had high levels of internal consistency, and a factor structure consisting of three lower-order factors (i.e. Physical, Psychological, and Social Concerns) that all loaded on a single higher-order (global Anxiety Sensitivity) factor. We also found that these Native American college students reported significantly greater overall ASI scores as well as greater levels of Psychological and Social Concerns relative to counterparts from the majority (Caucasian) culture. There were no significant differences detected for ASI physical threat concerns. In regard to gender, we found significant differences between males and females in terms of total and Physical Threat ASI scores, with females reporting greater levels, and males lesser levels, of overall anxiety sensitivity and greater fear of physical sensations: no significant differences emerged between genders for the ASI Psychological and Social Concerns dimensions. These gender differences did not vary by cultural group, indicating they were evident among Caucasian and Native Americans alike. We discuss the results of this investigation in relation to the assessment of anxiety sensitivity in American Indians and Alaska Natives, and offer directions for future research with the ASI in Native peoples. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. Dalhousie Univ, Dept Psychol, Halifax, NS B3H 3J5, Canada. RP Zvolensky, MJ (reprint author), W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. RI Stewart, Sherry /F-4088-2011 NR 73 TC 62 Z9 63 U1 5 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD APR PY 2001 VL 39 IS 4 BP 477 EP 493 DI 10.1016/S0005-7967(00)00010-3 PG 17 WC Psychology, Clinical SC Psychology GA 411DT UT WOS:000167483400008 PM 11280345 ER PT J AU Cariani, P AF Cariani, P TI Symbols and dynamics in the brain SO BIOSYSTEMS LA English DT Review DE adaptive systems; biological cybernetics; biological semiotics; dynamical systems; emergence; epistemology; evolutionary robotics; genetic code; neural code; neurocomputation; self-organization; symbols ID MATHEMATICAL MODEL; UNDERLIE BEHAVIOR; CELL ASSEMBLIES; NEURAL NETWORKS; INFORMATION; PITCH; COGNITION; LOOKING; ORIGIN; MEMORY AB The work of physicist and theoretical biologist Howard Pattee has focused on the roles that symbols and dynamics play in biological systems. Symbols, as discrete functional switching-states, are seen at the heart of all biological systems in the form of genetic codes. and at the core of all neural systems in the form of informational mechanisms that switch behavior. They also appear in one form or another in all epistemic systems, from informational processes embedded in primitive organisms to individual human beings to public scientific models. Over its course, Pattee's work has explored (1) the physical basis of informational functions (dynamical vs. rule-based descriptions, switching mechanisms, memory, symbols), (2) the functional organization of the observer (measurement, computation), (3) the means by which information can be embedded in biological organisms fur purposes of self-construction and representation (as codes modeling relations, memory. symbols), and (4) the processes by which new structures and functions can emerge over time. We discuss how these concepts can be applied to a high-level understanding of the brain. Biological organisms constantly reproduce themselves as well as their relations with their environs. The brain similarly can be seen as a self-producing, sell-regenerating neural signaling system and as an adaptive informational system that interacts with its surrounds in order to steer behavior. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC3054] NR 155 TC 23 Z9 26 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0303-2647 EI 1872-8324 J9 BIOSYSTEMS JI Biosystems PD APR-MAY PY 2001 VL 60 IS 1-3 BP 59 EP 83 DI 10.1016/S0303-2647(01)00108-3 PG 25 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 431LZ UT WOS:000168633900006 PM 11325504 ER PT J AU Rosenzweig, M Connole, M Glickman, R Yue, SPS Noren, B DeMaria, M Johnson, RP AF Rosenzweig, M Connole, M Glickman, R Yue, SPS Noren, B DeMaria, M Johnson, RP TI Induction of cytotoxic T lymphocyte and antibody responses to enhanced green fluorescent protein following transplantation of transduced CD34(+) hematopoietic cells SO BLOOD LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; COLONY-STIMULATING FACTOR; GENE-TRANSFER; BONE-MARROW; PROGENITOR CELLS; NONHUMAN-PRIMATES; PERIPHERAL-BLOOD; STEM-CELLS; AUTOLOGOUS TRANSPLANTATION; ADENOVIRUS VECTORS AB Genetic modification of hematopoietic stem cells often results in the expression of foreign proteins in pluripotent progenitor cells and their progeny. However, the potential for products of foreign genes introduced into hematopoietic stem cells to induce host immune responses is not well understood. Gene marking and induction of immune responses to enhanced green fluorescent protein (eGFP) were examined in rhesus macaques that underwent nonmyeloablative irradiation followed by infusions of CD34(+) bone marrow cells transduced with a retroviral vector expressing eGFP, CD34(+) cells were obtained from untreated animals or from animals treated with recombinant human granulocyte colony-stimulating factor (G-CSF) alone or G-CSF and recombinant human stem cell factor. Levels of eGFP-expressing cells detected by flow cytometry peaked at 0.1% to 0.5% of all leukocytes 1 to 4 weeks after transplantation. Proviral DNA was detected in 0% to 17% of bone marrow-derived colony-forming units at periods of 5 to 18 weeks after transplantation. However, 5 of 6 animals studied demonstrated a vigorous eGFP-specific cytotoxic T lymphocyte (CTL) response that was associated with a loss of genetically modified cells in peripheral blood, as demonstrated by both flow cytometry and polymerase chain reaction. The eGFP-specific CTL responses were MHC-restricted, mediated by CD8(+) lymphocytes, and directed against multiple epitopes, eGFP-specific CTLs were able to efficiently lyse autologous CD34(+) cells expressing eGFP, Antibody responses to eGFP were detected in 3 of 6 animals. These data document the potential for foreign proteins expressed in CD34(+) hematopoietic cells and their progeny to induce antibody and CTL responses in the setting of a clinically applicable transplantation protocol. (Blood, 2001;97:1951-1959) (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. FU NCI NIH HHS [CA73473]; NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI39423] NR 45 TC 113 Z9 115 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2001 VL 97 IS 7 BP 1951 EP 1959 DI 10.1182/blood.V97.7.1951 PG 9 WC Hematology SC Hematology GA 429KM UT WOS:000168516000009 PM 11264158 ER PT J AU Gazda, H Lipton, JM Willig, TN Ball, S Niemeyer, CM Tchernia, G Mohandas, N Daly, MJ Ploszynska, A Orfali, KA Vlachos, A Glader, BE Rokicka-Milewska, R Ohara, A Baker, D Pospisilova, D Webber, A Viskochil, DH Nathan, DG Beggs, AH Sieff, CA AF Gazda, H Lipton, JM Willig, TN Ball, S Niemeyer, CM Tchernia, G Mohandas, N Daly, MJ Ploszynska, A Orfali, KA Vlachos, A Glader, BE Rokicka-Milewska, R Ohara, A Baker, D Pospisilova, D Webber, A Viskochil, DH Nathan, DG Beggs, AH Sieff, CA TI Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease SO BLOOD LA English DT Article ID RIBOSOMAL-PROTEIN S19; HEART TUBE FORMATION; TRANSCRIPTION FACTOR; VENTRAL MORPHOGENESIS; HUMAN GENOME; GENE; 19Q13; IDENTIFICATION; MUTATIONS; ENDODERM AB Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia that usually presents early in infancy and is inherited in 10% to 20% of cases. Linkage analysis has shown that DBA in many of both dominant and recessive DBA families mapped to chromosome 19q13.2 leading to the cloning of a gene on chromosome 19q13.2 that encodes a ribosomal protein, RPS19. However, subsequently, mutations of the RPS19 gene have only been identified in 25% of all patients with DBA. This study analyzed 14 multiplex DBA families, 9 of which had 19q13.2 haplotypes inconsistent with 19q linkage. A genome-wide search for linked loci suggested the presence of a second DBA locus in a 26.4-centimorgan (cM) interval on human chromosome 8p. Subsequently, 24 additional DBA families were ascertained and all 38 families were analyzed with additional polymorphic markers on chromosome 8p. In total, 18 of 38 families were consistent with linkage to chromosome 8p with a maximal LOD score with heterogeneity of 3.55 at D8S277 assuming 90% penetrance. The results indicate the existence of a second DBA gene in the 26.4-cM telomeric region of human chromosome 8p23.3-p22, most likely within an 8.1-cM interval flanked by D8S518 and D8S1825. Seven families were inconsistent with linkage to 8p or 19q and did not reveal mutations in the RPS19 gene, suggesting further genetic heterogeneity. (Blood. 2001;97:2145-2150) (C) 2001 by The American Society of Hematology. C1 Dana Farber Canc Inst, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Mt Sinai Sch Med, Div Pediat Hematol Oncol, New York, NY USA. Hop Bicetre, Assitance Publ Hop Paris, Dept Hematol, Paris, France. Fac Med, Paris, France. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. Univ London St Georges Hosp, Sch Med, Dept Haematol, London SW17 0RE, England. Univ Freiburg, Childrens Hosp, D-7800 Freiburg, Germany. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. Univ Gdansk, Dept Pediat Hematol & Oncol, PL-80952 Gdansk, Poland. Stanford Univ, Sch Med, Div Pediat Hematol Oncol, Stanford, CA 94305 USA. Warsaw Sch Med, Dept Pediat Hematol Oncol, Warsaw, Poland. Toho Univ, Sch Med, Dept Pediat, Tokyo, Japan. Princess Margaret Hosp Children, Dept Pediat Haematol Oncol, Perth, WA, Australia. Univ Hosp, Dept Pediat, Olomouc, Czech Republic. Univ Utah, Sch Med, Div Med Genet, Salt Lake City, UT USA. RP Gazda, H (reprint author), Dana Farber Canc Inst, Div Pediat Hematol & Oncol, Rm M615,44 Binney St, Boston, MA 02115 USA. OI Beggs, Alan/0000-0001-8818-0568 FU FIC NIH HHS [F05 TW05395]; NIAMS NIH HHS [AR44345, KO2 AR02026]; NIDDK NIH HHS [DK 26263] NR 28 TC 48 Z9 48 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2001 VL 97 IS 7 BP 2145 EP 2150 DI 10.1182/blood.V97.7.2145 PG 6 WC Hematology SC Hematology GA 429KM UT WOS:000168516000034 PM 11264183 ER PT J AU Titone, D Wingfield, A Caplan, D Waters, G Prentice, K AF Titone, D Wingfield, A Caplan, D Waters, G Prentice, K TI Memory and encoding of spoken discourse following right hemisphere damage: Evidence from the Auditory Moving Window (AMW) technique SO BRAIN AND LANGUAGE LA English DT Article ID NORMALLY AGING ADULTS; CEREBRAL BLOOD-FLOW; BRAIN-DAMAGE; CONTEXTUAL INFORMATION; RESOURCE-ALLOCATION; AGE-DIFFERENCES; TEXT RECALL; MAIN IDEAS; COMPREHENSION; SPEECH AB We investigated the hypotheses that impaired discourse processing following right hemisphere damage is mediated by task difficulty and is associated with deficits in discourse encoding. Spoken discourse passages differing in contextual predictability were presented to right hemisphere-damaged (RHD) patients and to non-brain-damaged (NBD) controls for subsequent recall using the Auditory Moving Window paradigm. To manipulate processing difficulty, speech segments were of normal or accelerated speech rates. The recall results showed that RHD adults recalled less than NBD controls overall and failed to recall major idea units better than minor idea units for high predictability passages presented at accelerated speech rates. Both RHD patients and NBD controls failed to recall major idea units better than minor idea units for low predictability passages, regardless of speech rate. The encoding results showed that RHD adults were both slower overall and differentially slower than NBD controls when listening to accelerated passage segments. Taken together, the encoding and recall results are consistent with the view that extracting passage gist under difficult listening conditions is especially vulnerable for patients with right hemisphere strokes. (C) 2001 Academic Press. C1 McLean Hosp, Psychol Res Lab, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Brandeis Univ, Volen Ctr Complex Syst, Waltham, MA 02254 USA. Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. RP Titone, D (reprint author), McLean Hosp, Psychol Res Lab, Mailman Res Ctr, Belmont, MA 02478 USA. FU NIA NIH HHS [AG04517]; NIDCD NIH HHS [DC00942]; NIMH NIH HHS [R03 MH60272] NR 57 TC 8 Z9 9 U1 3 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD APR PY 2001 VL 77 IS 1 BP 10 EP 24 DI 10.1006/brln.2000.2419 PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 416BP UT WOS:000167760100002 PM 11247653 ER PT J AU Glaspy, J Jadeja, JS Justice, G Kessler, J Richards, D Schwartzberg, L Rigas, J Kuter, D Harmon, D Prow, D Demetri, G Gordon, D Arseneau, J Saven, A Hynes, H Boccia, R O'Byrne, J Colowick, AB AF Glaspy, J Jadeja, JS Justice, G Kessler, J Richards, D Schwartzberg, L Rigas, J Kuter, D Harmon, D Prow, D Demetri, G Gordon, D Arseneau, J Saven, A Hynes, H Boccia, R O'Byrne, J Colowick, AB TI A dose-finding and safety study of novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia in patients receiving multicycle chemotherapy SO BRITISH JOURNAL OF CANCER LA English DT Article DE anaemia; cancer; chemotherapy; darbepoetin alfa; solid tumours; transfusion ID QUALITY-OF-LIFE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; COMMUNITY ONCOLOGY; EPOETIN-ALPHA; ANEMIA; CANCER; CYTOKINES; FATIGUE; DISEASE; IMPACT AB Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from FHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life, rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg(-1) wk(-1)) in each cohort, Patients were monitored for adverse events? including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up, A dose-response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 meg kg(-1) wk(-1) cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl(-1) respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing. (C) 2001 Cancer Research Campaign. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Hematol Oncol Associates Jacksonville, Jacksonville, FL 32207 USA. Pacific Coast Hematol Oncol Med Grp, Fountain Valley, CA 92708 USA. Virginia Oncol Associates, Newport News, VA USA. Tyler Canc Ctr, Tyler, TX 75702 USA. West Clin, Memphis, TN 38117 USA. Dartmouth Coll, Sch Med, Norris Canc Ctr, Lebanon, NH 03756 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Texas Canc Care, Ft Worth, TX 76104 USA. Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. San Antonio Tumor & Blood Clin, San Antonio, TX 78215 USA. Albany Reg Canc Ctr, Albany, NY 12208 USA. Scripps Clin, La Jolla, CA 92037 USA. Canc Ctr Kansas, Wichita, KS 67214 USA. Associates Oncol & Hematol, Rockville, MD USA. Amgen Inc, Thousand Oaks, CA 91329 USA. RP Glaspy, J (reprint author), Univ Calif Los Angeles, Sch Med, 200 Med Plaza,Suite 120, Los Angeles, CA 90024 USA. NR 22 TC 40 Z9 40 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR PY 2001 VL 84 SU 1 BP 17 EP 23 DI 10.1054/bjoc.2001.1748 PG 7 WC Oncology SC Oncology GA 432NV UT WOS:000168698700003 PM 11308270 ER PT J AU Demetri, GD AF Demetri, GD TI Anaemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy SO BRITISH JOURNAL OF CANCER LA English DT Article DE anaemia; cancer; chemotherapy; radiotherapy; recombinant human erythropoietin; darbepoetin alfa ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CHEMOTHERAPY-INDUCED ANEMIA; QUALITY-OF-LIFE; PRETREATMENT HEMOGLOBIN; STIMULATING PROTEIN; COMMUNITY ONCOLOGY; BLOOD-TRANSFUSION; EPOETIN-ALPHA; LOCAL-CONTROL; DOUBLE-BLIND AB Anaemia is a common occurrence in patients with cancer and contributes to the clinical symptomatology and reduced quality of life (QOL) seen in cancer patients. Many aspects of reduced QOL, including fatigue, are known to be associated with suboptimally low levels of haemoglobin. Even mild-to-moderate anaemia adversely affects patient-reported QOL parameters. Red blood cell transfusions are associated with many real and perceived risks, inconveniences, costs, and only temporary benefits. Recombinant human erythropoietin (rHuEPO) is an effective therapy to increase haemoglobin values in over half of anaemic cancer patients receiving concurrent chemotherapy. These increased haemoglobin values are closely correlated with improvements in QOL. Despite these objectively defined benefits, less than 50% of anaemic patients undergoing cytotoxic chemotherapy receive rHuEPO, in contrast to patients with chronic renal failure on dialysis, where anaemia is universally and aggressively treated to more optimal haemoglobin values. However, there are several barriers that may limit more widespread use of rHuEPO. These include inconvenience associated with frequent dosing; failure of a large proportion (40 to 50%) of patients to respond; relatively slow time to response; absence of reliable early indicators of response; and current lack of rigorous pharmacoeconomic data demonstrating cost-effectiveness. Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP) that is biochemically distinct from rHuEPO, and which has been proven to stimulate red blood cell production. The molecule has a 3-fold longer half-life and increased biological activity that will allow less frequent dosing, facilitating improved management of the anaemia of cancer. With this new option for therapy. further avenues of investigation should lead to renewed interest in the clinical benefits of optimal haemoglobin levels for patients with cancer. (C) 2001 Cancer Research Campaign. C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 44 Binney St, Boston, MA 02115 USA. NR 53 TC 65 Z9 66 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR PY 2001 VL 84 SU 1 BP 31 EP 37 DI 10.1054/bjoc.2001.1750 PG 7 WC Oncology SC Oncology GA 432NV UT WOS:000168698700005 PM 11308272 ER PT J AU Tsuang, MT Stone, WS Faraone, SV AF Tsuang, MT Stone, WS Faraone, SV TI Genes, environment and schizophrenia SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 8th Congress of the International-Federation-of-Psychiatric-Epidemiology CY MAR 06-09, 1999 CL TAIPEI, TAIWAN SP Int Federat Psychiat Epidemiol, Acad Sinica, Inst Biomed Sci, Taiwanese Soc Psychiat ID FINNISH ADOPTIVE FAMILY; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; OBSTETRIC COMPLICATIONS; DSM-III; TWIN CONCORDANCE; GENOME SCAN; GENETICS; RELATIVES; VULNERABILITY AB Background Data from family,twin and adoption studies show overwhelming evidence of a substantial genetic component in schizophrenia and although molecular genetic studies have been more difficult to replicate, recent improvements in technology have resulted in the implication of genes at several chromosomal loci. Nevertheless, it remains clear that environmental factors both add to and interact with genetic factors to produce the disorder. Aims To incorporate genetic and environmental risk factors into a neurodevelopmental model in order to conceptualise the liability to schizophrenia. Method A representative selection of the literature related to this issue is reviewed, together with a reformulation of Meehl's term 'schizotaxia' to describe the liability to the disorder. Results The literature supports a multi-factorial view of the liability to schizophrenia, which includes both genetic and environmental components. Conclusions Schizotaxia provides a useful way to conceptualise both the liability for schizophrenia, and also the development of treatment strategies aimed at the eventual prevention of the illness. Declaration of interest None. Funding detailed in Acknowledgements. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. NR 79 TC 63 Z9 64 U1 3 U2 19 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD APR PY 2001 VL 178 SU 40 BP S18 EP S24 DI 10.1192/bjp.178.40.s18 PG 7 WC Psychiatry SC Psychiatry GA 419KU UT WOS:000167948600005 ER PT J AU Kelly, K AF Kelly, K TI How to find medical information on the Internet. A print and online tutorial for the healthcare professional and consumer. SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD APR PY 2001 VL 89 IS 2 BP 238 EP 240 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA 544DE UT WOS:000175142300016 ER PT J AU Chang, BK Backstrand, KH Ng, AK Silver, B Hitchcock, SL Mauch, PM AF Chang, BK Backstrand, KH Ng, AK Silver, B Hitchcock, SL Mauch, PM TI Significance of epitrochlear lymph node involvement in Hodgkin disease SO CANCER LA English DT Article DE Hodgkin disease; epitrochlear lymph nodes; brachial lymph nodes; radiation therapy AB BACKGROUND. Epitrochlear involvement in Hodgkin disease (HD) is a rare event, with only limited data available describing this unique presentation, its treatment, and long term outcome. METHODS. Between 1968 and 1997, 1180 patients with clinical stage (CS) IA-IIB HD were treated at the Harvard Longwood Area Hospitals, among whom 11 were identified to have presented with epitrochlear lymphadenopathy (1%). Together with 6 CS III-IV patients also with clinically involved epitrochlear lymph nodes at diagnosis, these 17 patients form the basis of the current study. The clinical characteristics, histopathologic distribution, and treatment details are described. Two radiation therapy techniques were used: the "single field" and "separate-field" techniques. The median dose to the epitrochlear region was 3600 centigrays. Survival outcome was calculated by the Kaplan-Meier method. The median followup was 17 years. RESULTS. The actuarial 15-year freedom from recurrence, cause specific survival, and overall survival (OS) rates for the 17 patients were 70%, 88%, and 70%, respectively. Among the CS IA-IIB patients, the 15-year OS rates of the 1169 patients and II patients without and with epitrochlear involvement were 80% and 90%, respectively. Two of the 11 CS IPI-IIB and 3 of the 6 CS III-TV patients experienced recurrence. None of the recurrences involved the epitrochlear or ipsilateral brachial region regardless of the treatment technique, and no complications from the local radiation therapy were observed. CONCLUSIONS, Feasible and effective radiation therapy techniques are available for patients with HD with epitrochlear involvement. If appropriately treated, the prognosis of patients with this unique presentation appears to be similar to that of other HD patients. (C) 2001 American Cancer Society. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, ASB1-L2,75 Francis St, Boston, MA 02115 USA. NR 14 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 0008-543X J9 CANCER JI Cancer PD APR 1 PY 2001 VL 91 IS 7 BP 1213 EP 1218 PG 6 WC Oncology SC Oncology GA 414CF UT WOS:000167647800004 PM 11283919 ER PT J AU Wallace, SR Oken, MM Lunetta, KL Panoskaitsis-Mortari, A Masellis, AM AF Wallace, SR Oken, MM Lunetta, KL Panoskaitsis-Mortari, A Masellis, AM TI Abnormalities of bone marrow mesenchymal cells in multiple myeloma patients SO CANCER LA English DT Article DE mesenchymal cell; multiple myeloma; bone marrow; cytokine; growth factors ID HYALURONAN RECEPTOR RHAMM; STROMAL CELLS; ADHESION MOLECULES; MEDIATED MOTILITY; INTERLEUKIN-6 SECRETION; TUMOR-CELLS; B-CELLS; EXPRESSION; DEXAMETHASONE; LINES AB BACKGROUND. The importance of the bone marrow microenvironment in multiple myeloma is receiving increasing attention. Recent studies have suggested the importance of cytokine production and cell-cell contact by bone marrow stromal cells in the survival of myeloma cells. METHODS. In the current study, the authors examined bone marrow mesenchymal progenitor cell (MPC) cultures derived from eight multiple myeloma patients (mean age, 58 years) and nine normal donors (mean age, 61 years), with emphasis on cell surface antigens, cytokine, and growth factor expression. RESULTS. The authors have found, based on analysis of cellular receptors, growth factors, and cytokine expression, that myeloma MPCs are phenotypically and functionally distinguishable from normal donor MPCs. Immunofluorescence analysis of MPC monolayers shows that myeloma MPC cultures expressed reduced cell surface vascular cell adhesion molecule-1 and fibronectin, in contrast with the strong expression found on normal donor MPCs. Furthermore, a subset of myeloma MPCs strongly express intracellular receptor for hyaluronan-mediated motility, whereas normal MPCs do not. Cytokine expression in bone marrow MPC cultures was examined by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay. Bone marrow MPCs constitutively express interleukin (IL)-1 beta, IL-6, granulocyte colony-stimulating factor (G-CSF), granule cyte macrophage (GM)-CSF, stem cell factor (SCF), and tumor necrosis factor (TNF)-alpha.. In comparison to normal MPCs, multiple myeloma MPCs express increased basal levels of IL-1 beta and TNF-alpha. In vitro exposure of MPC cultures to dexamethasone resulted in the down-regulation of IL-6, G-CSF, and GM-CSF in both normal and myeloma MPC cultures. However, dexamethasone treatment significantly increased expression of SCF-1 in myeloma MPCs. CONCLUSIONS. in myeloma, bone marrow stromal cells provide paracrine factors, through cytokine production and cell-cell contact, which play a role in plasma cell growth and survival. The authors' data indicate differences in bone marrow MPCs, which may be biologically relevant to the growth and survival of myeloma plasma cells. (C) 2001 American Cancer Society. C1 Abbott NW Hosp, Virginia Piper Canc Inst 30419, Minneapolis, MN 55407 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. RP Masellis, AM (reprint author), Abbott NW Hosp, Virginia Piper Canc Inst 30419, 800 E 28th St, Minneapolis, MN 55407 USA. NR 44 TC 69 Z9 75 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 0008-543X J9 CANCER JI Cancer PD APR 1 PY 2001 VL 91 IS 7 BP 1219 EP 1230 DI 10.1002/1097-0142(20010401)91:7<1219::AID-CNCR1122>3.0.CO;2-1 PG 12 WC Oncology SC Oncology GA 414CF UT WOS:000167647800005 PM 11283920 ER PT J AU Meropol, NJ Niedzwiecki, D Hollis, D Schilsky, RL Mayer, RJ AF Meropol, NJ Niedzwiecki, D Hollis, D Schilsky, RL Mayer, RJ CA Canc & Leukemia Grp B TI Phase II study of oral eniluracil, 5-fluorouracil, and leucovorin in patients with advanced colorectal carcinoma SO CANCER LA English DT Article DE dihydropyrimidine dehydrogenase (DPD); biochemical modulation; fluoropyrimidines; fluorinated pyrimidines; colorectal carcinoma; eniluracil; ethynyluracil; 5-fluorouracil ID DIHYDROPYRIMIDINE DEHYDROGENASE; 5-ETHYNYLURACIL 776C85; FLUOROURACIL; CANCER; THERAPY AB BACKGROUND. The oral administration of 5-fluorouracil (5-FU) is hindered by erratic bioavailability due to catabolism of 5-FU by the enzyme dihydropyrimidine dehydrogenase (DPD) in the gastrointestinal tract. Eniluracil is a potent inactivator of DPD which results in 100% oral bioavailability of 5-FU. Leucovorin (LV) is another biochemical modulator of 5-FU that potentiates inhibition of thymidylate synthase, the primary target of 5-FU. The goal of this study was to determine the antitumor activity and toxicity of an oral regimen containing eniluracil, 5-FU, and LV in patients with colorectal carcinoma. METHODS. Sixty eligible patients who had previously untreated, measurable, metastatic colorectal carcinoma were treated with oral eniluracil 50 mg on Days 1-7, 5-FU 20 mg/m(2) on Days 2-6, and LV 50 mg on Days 2-6. Cycles were repeated at 28-day intervals. RESULTS. The overall response rate was 13% (95% confidence interval [CI] = 6, 25%), with 1 complete response and 7 partial responses. Three additional patients had partial responses that were not confirmed at subsequent evaluations. The median time to progression of disease was 4.4 months (95% CI = 3.45, 7.69) and the median survival time was 12.6 months (95% CI = 9.1, 14.75). Grade 3-5 toxicity (1 toxic death) occurred in 51 patients (85%). Grade 4 neutropenia occurred in 25 patients (42%), and 18 patients (30%) had Grade 3-4 diarrhea. Twenty-one patients (35%) were hospitalized for toxicity, and 12 (20%) had febrile neutropenia. Baseline creatinine clearance was associated inversely with severe toxicity (P = 0.001). CONCLUSIONS. Although antitumor activity was observed, the frequent occurrence of severe toxicity with this regimen limited its clinical utility. Alternate schedules with a more favorable therapeutic index are undergoing clinical testing and should pursued. The high level of toxicity observed with orally administered low dose 5-FU underscored the potency of eniluracil as a biochemical modulator. (C) 2001 American Cancer Society. C1 Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. CALGB Stat Ctr, Durham, NC USA. Univ Chicago, Ctr Canc, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Meropol, NJ (reprint author), Fox Chase Canc Ctr, Div Med Sci, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [CA31946-19] NR 20 TC 7 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 2001 VL 91 IS 7 BP 1256 EP 1263 DI 10.1002/1097-0142(20010401)91:7<1256::AID-CNCR1126>3.0.CO;2-V PG 8 WC Oncology SC Oncology GA 414CF UT WOS:000167647800009 PM 11283924 ER PT J AU Xu, LL Wain, JC Miller, DP Thurston, SW Su, L Lynch, TJ Christiani, DC AF Xu, LL Wain, JC Miller, DP Thurston, SW Su, L Lynch, TJ Christiani, DC TI The NAD(P)H : quinone oxidoreductase 1 gene polymorphism and lung cancer: Differential susceptibility based on smoking behavior SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DT-DIAPHORASE; NAD(P)H; IDENTIFICATION; ASSOCIATION; EXPRESSION; MUTATION; GENOTYPE; DIOXIN; CDNA; NQO1 AB We conducted a hospital-based case-control study of 814 lung cancer patients and 1123 controls to examine the association of the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene polymorphism with lung cancer susceptibility, Using PCR-RFLP genotyping assay techniques, we analyzed DNA samples to detect the variant forms of the NQO1 gene in exon 6 on chromosome 16q. We examined the relationship between lung cancer odds and NQO1 genotypes after adjusting for age, gender, and smoking behavior using generalized additive modeling. We found no overall association between NQO1 genotypes and lung cancer susceptibility, regardless of age, gender, family history of cancer, or histological cell type. However, our data demonstrated that in both former and current smokers, there was an association between NQO1 genotypes and lung cancer susceptibility that was dependent upon cigarette smoking duration and smoking intensity. For both current and former smokers, smoking intensity was more important in predicting cancer risk than smoking duration for all of the genotypes. Among former smokers, individuals with the T/T genotype mere predicted to have a greater cancer risk than those with the C/C genotype for smoking durations up to 37 years. The predicted cancer risk for former smokers with the C/T versus T/T genotype depended on both smoking intensity and smoking duration. Our results support the concept that differential susceptibility to lung cancer is a function of both an inheritable trait in NQO1 metabolism and individual smoking characteristics. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES00002, ES/CA06409]; PHS HHS [T3207069] NR 26 TC 56 Z9 60 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2001 VL 10 IS 4 BP 303 EP 309 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 427BH UT WOS:000168384600003 PM 11319169 ER PT J AU George, DJ Shepard, TF Ma, J Giovannucci, E Kantoff, PW Stampfer, MJ AF George, DJ Shepard, TF Ma, J Giovannucci, E Kantoff, PW Stampfer, MJ TI PTEN polymorphism (IVS4) is not associated with risk of prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Adult Oncol,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP George, DJ (reprint author), Dana Farber Canc Inst, Dept Oncol, 44 Binney St, Boston, MA 02115 USA. NR 6 TC 14 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2001 VL 10 IS 4 BP 411 EP 412 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 427BH UT WOS:000168384600019 PM 11319185 ER PT J AU Jacobs, A Tjuvajev, JG Dubrovin, M Akhurst, T Balatoni, J Beattie, B Joshi, R Finn, R Larson, SM Herrlinger, U Pechan, PA Chiocca, EA Breakefield, XO Blasberg, RG AF Jacobs, A Tjuvajev, JG Dubrovin, M Akhurst, T Balatoni, J Beattie, B Joshi, R Finn, R Larson, SM Herrlinger, U Pechan, PA Chiocca, EA Breakefield, XO Blasberg, RG TI Positron emission tomography-based imaging of transgene expression mediated by replication-conditional, oncolytic herpes simplex virus type 1 mutant vectors in vivo SO CANCER RESEARCH LA English DT Article ID THYMIDINE KINASE GENE; EXPERIMENTAL BRAIN-TUMORS; RIBONUCLEOTIDE REDUCTASE; IMMUNOCOMPETENT RATS; ANTITUMOR-ACTIVITY; MALIGNANT GLIOMAS; VIRAL MUTANT; THERAPY; GANCICLOVIR; GROWTH AB To evaluate the efficiency of gene delivery in gene therapy strategies for malignant brain tumors, it is important to determine the distribution and magnitude of transgene expression in target tumor cells over time, Here, we assess the time- and vector dose-dependent kinetics of recombinant herpes simplex virus (HSV)-1 vector-mediated gene expression and vector replication in culture and irt vivo by a recently developed radiotracer method for noninvasive imaging of gene expression (J. G. Tjuvajev et al., Cancer Res., 55: 61.26-6132, 1995), The kinetics of viral infection of rat 91, gliosarcoma cells by the replication-conditional HSV-1 vector, hrR3, was studied by measuring the accumulation rate of 2-[C-14]-fluoro-5-iodo-1-beta -D-arabinofurano (FIAU), a selective substrate for viral thymidine kinase (TK). The level of viral TR activity in 9L cells was monitored by the radiotracer assay to assess various vector doses and infection times, allowing vector replication and spread. In parallel, viral yields and levels of Escherichia coli beta -galactosidase activity were assessed quantitatively. To study vector replication, spread and HSV-1-tk and lacZ gene coexpression in vivo, first- or second-generation recombinant HSV-1 vectors (hrR3 or MGH-1) were injected into s.c. growing mt 9L or human U87 Delta EGFR gliomas in nude rats at various times (8 h to 8 days) and at various vector doses [1 x 10(6) to 2 x 10(9) plaque-forming units (PFUs)] Drier to imaging. For noninvasive assessment of HSV-l-tk gene expression (I-124-labeled FIAU % dose/g), 0.15 mCi of I-124-labeled FIAU was injected i.v. 8 h after the last vector administration, and FIAU positron emission tomography (PET) was performed 48 h later, For the assessment of HSV-l-tk and lacZ gene coexpression, 0.2 mCi of I-131-labeled FIAU was injected i.v, 24 h after the last vector administration. Forty-eight h later, animals were killed, and tumors were dissected for quantitative autoradiographical and histochemical assessment of regional distribution of radioactivity (TK expression measured as I-131-labeled FIAU % dose/g) and coexpressed lacZ gene activity. The rates of FIAU accumulation (Ki) in hrR3-infected 91, cells in culture, which reflect the levels of HSV-l-tk gene expression, ranged between 0.12 and 3.4 ml/g/min. They increased in a vector dose- and infection time-dependent manner and correlated with the virus yield (PFUs/ml), where the PFUs:Ki ratios remained relatively constant over time, Moreover, a linear relationship was observed between lacZ gene expression and FIAU accumulation 5-40 h after infection of 9L cells with a multiplicity of infection of 1.5, At later times (>52 h postinjection), high vector doses (multiplicity of infection, 1.5) led to a decrease of FIAU accumulation rates, viral yield, and cell pellet weights, indicating vector-mediated cell toxicity, Various levels of HSV-l-tk gene expression could be assessed by FIAU-PET after in vivo infection of s.c. tumors. The levels of FIAU accumulation were comparatively low (similar to ranging from 0.00013 to 0.003% injected dose/g) and were spatially localized; this may reflect viral-induced cytolysis of infected tumor cells and limited lateral spread of the virus, Image coregistration of tumor histology, HSV-l-tk related radioactivity (assessed by autoradiography), and lacZ gene expression (assessed by beta -galactosidase staining) demonstrated a characteristic pattern of gene expression around the injection sites. A rim of lacZ gene expression immediately adjacent to necrotic tumor areas was observed, and this zone was surrounded by a narrow band of HSV-l-tk-related radioactivity, primarily in viable-appearing tumor tissue. These results demonstrate that recombinant HSV-I vector-mediated HSV-l-tk gene expression can be monitored noninvasively by PET, where the areas of FIAU-derived radioactivity identify the viable portion of infected tumor tissue that retains FIAU accumulation ability, and that the accumulation rate of FIAU in culture, Ki, reflects the number of HSV-1 viral particles in the infected tumor cell population [4.1 +/- 0.6 x 106 PFUs/Ki unit PFUs + ml/min/g)l. Moreover, time-dependent and spatial relationships of HSV-l-tk and lacZ gene coexpression in culture and in vivo indicate the potential for indirect in vivo imaging of therapeutic gene expression in tumor tissue infected with any recombinant HSV-1 vector where a therapeutic gene is substituted for the lacZ gene. C1 Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurooncol Unit, Boston, MA USA. Max Planck Inst Neurol Res, D-50931 Cologne, Germany. RP Blasberg, RG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. EM blasberg@neurol.mskcc.org RI Beattie, Bradley/K-8981-2012 OI Beattie, Bradley/0000-0001-9891-8271 FU NCI NIH HHS [R01CA76117, R01CA60706, CA69246] NR 64 TC 123 Z9 128 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2001 VL 61 IS 7 BP 2983 EP 2995 PG 13 WC Oncology SC Oncology GA 419UM UT WOS:000167967100032 PM 11306477 ER PT J AU Wu, A Mazumder, A Martuza, RL Liu, X Thein, M Meehan, KR Rabkin, SD AF Wu, A Mazumder, A Martuza, RL Liu, X Thein, M Meehan, KR Rabkin, SD TI Biological purging of breast cancer cells using an attenuated replication-competent herpes simplex virus in human hematopoietic stem cell transplantation SO CANCER RESEARCH LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; BONE-MARROW TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; TYPE-1 MUTANT G207; PERIPHERAL-BLOOD; TUMOR-CELLS; AUTOLOGOUS TRANSPLANTATION; PROGENITOR CELLS; ANTITUMOR IMMUNITY; SAFETY EVALUATION AB Autologous hematopoietic stem cell transplantation after myelosuppressive chemotherapy is used for the treatment of high-risk breast cancer and other solid tumors. However, contamination of the autologous graft with tumor cells may adversely affect outcomes. Human hematopoietic bone marrow cells are resistant to herpes simplex virus type 1 (HSV-1) replication, whereas human breast cancer cells are sensitive to HSV-1 cytotoxicity. Therefore, we examined the utility of G207, a safe replication-competent multimutated HSV-1 vector, as a biological purging agent for breast cancer in the setting of stem cell transplantation. G207 infection of human bone marrow cells had no effect on the proportion or clonogenic capacity of CD34(+) cells but did enhance the proliferation of bone marrow cells in culture and the proportion of CD14(+) and CD38(+) cells. On the other hand, G207 at a multiplicity of infection of 0.1 was able to purge bone marrow of contaminating human breast cancer cells. Because G207 also stimulates the proliferation of human hematopoietic cells, it overcomes a limitation of other purging methods that result in delayed reconstitution of hematopoiesis. The efficient infection of human bone marrow cells in the absence of detected toxicity suggests that HSV vectors may also prove useful for gene therapy to hematopoietic progenitor cells. C1 Georgetown Univ, Ctr Med, Mol Neurosurg Lab, Washington, DC 20007 USA. Georgetown Univ, Ctr Med, Bone Marrow Transplantat Program, Washington, DC 20007 USA. Georgetown Univ, Ctr Med, Dept Neurosurg, Washington, DC 20007 USA. Georgetown Univ, Ctr Med, Dept Microbiol & Immunol, Washington, DC 20007 USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp East, Mol Neurosurg Lab, 13th St,Bldg 149,Box 17, Charlestown, MA 02129 USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NINDS NIH HHS [R01-NS32677] NR 66 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2001 VL 61 IS 7 BP 3009 EP 3015 PG 7 WC Oncology SC Oncology GA 419UM UT WOS:000167967100035 PM 11306480 ER PT J AU Hideshima, T Richardson, P Chauhan, D Palombella, VJ Elliott, PJ Adams, J Anderson, KC AF Hideshima, T Richardson, P Chauhan, D Palombella, VJ Elliott, PJ Adams, J Anderson, KC TI The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; CANCER-THERAPY; ADHESION; DEATH; ACTIVATION; TUMOR; INTERLEUKIN-6; THALIDOMIDE; EXPRESSION; INDUCTION AB Human multiple myeloma (MM) is a presently incurable hematological malignancy, and novel biologically based therapies are urgently needed. Proteasome inhibitors represent a novel potential anticancer therapy. In this study, we demonstrate that the proteasome inhibitor PS-341 directly inhibits proliferation and induces apoptosis of human MM cell lines and freshly isolated patient MM cells; inhibits mitogen-activated protein kinase growth signaling in MM cells; induces apoptosis despite induction of p21 and p27 in both p53 wild-type and p53 mutant MM cells; overcomes drug resistance; adds to the anti-MM activity of dexamethasone; and overcomes the resistance to apoptosis in MM cells conferred by interleukin-6. PS-341 also inhibits the paracrine growth of human MM cells by decreasing their adherence to bone marrow stromal cells (BMSCs) and related nuclear factor KB-dependent induction of interleukin-6 secretion in BMSCs, as well as inhibiting proliferation and growth signaling of residual adherent MM cells. These data, therefore, demonstrate that PS-341 both acts directly on MM cells and alters cellular interactions and cytokine secretion in the BM millieu to inhibit tumor cell growth, induce apoptosis, and overcome drug resistance. Given the acceptable animal and human toxicity profile of PS-341, these studies provide the framework for clinical evaluation of PS-341 to improve outcome for patients with this universally fatal hematological malignancy. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Millenium Pharmaceut Inc, Cambridge, MA 02139 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU PHS HHS [P0-1 78378] NR 35 TC 1050 Z9 1101 U1 8 U2 72 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2001 VL 61 IS 7 BP 3071 EP 3076 PG 6 WC Oncology SC Oncology GA 419UM UT WOS:000167967100044 PM 11306489 ER PT J AU Tootell, RBH Hadjikhani, N AF Tootell, RBH Hadjikhani, N TI Where is 'dorsal V4' in human visual cortex? Retinotopic, topographic and functional evidence SO CEREBRAL CORTEX LA English DT Review ID MONKEY PRESTRIATE CORTEX; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HUMAN OCCIPITAL LOBE; MACAQUE MONKEY; AREA V4; RHESUS-MONKEY; CORTICAL CONNECTIONS; STRIATE CORTEX; EXTRASTRIATE CORTEX AB In flattened human visual cortex, we defined the topographic homologue of macaque dorsal V4 (the 'V4d topologue'), based on neighborhood relations among visual areas (i.e. anterior to V3A, posterior to MT+, and superior to ventral V4). Retinotopic functional magnetic resonance imaging (fMRI) data suggest that two visual areas ('LOC' and 'LOP') are included within this V4d topologue. Except for an overall bias for either central or peripheral stimuli (respectively), the retinotopy within LOC and LOP was crude or nonexistent. Thus the retinotopy in the human V4d topologue differed from previous reports in macaque V4d. Unlike some previous reports in macaque V4d, the human V4d topologue was not significantly color-selective. However, the V4d topologue did respond selectively to kinetic motion boundaries, consistent with previous human fMRI reports. Because striking differences were found between the retinotopy and functional properties of the human topologues of 'V4v' and 'V4d', it is unlikely that these two cortical regions are subdivisions of a singular human area 'V4'. C1 Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Tootell, RBH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU NEI NIH HHS [EY07980] NR 104 TC 171 Z9 171 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2001 VL 11 IS 4 BP 298 EP 311 DI 10.1093/cercor/11.4.298 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 413BP UT WOS:000167590300002 PM 11278193 ER PT J AU Hirayasu, Y Tanaka, S Shenton, ME Salisbury, DF DeSantis, MA Levitt, JJ Wible, C Yurgelun-Todd, D Kikinis, R Jolesz, FA McCarley, RW AF Hirayasu, Y Tanaka, S Shenton, ME Salisbury, DF DeSantis, MA Levitt, JJ Wible, C Yurgelun-Todd, D Kikinis, R Jolesz, FA McCarley, RW TI Prefrontal gray matter volume reduction in first episode schizophrenia SO CEREBRAL CORTEX LA English DT Article ID 1ST-EPISODE SCHIZOPHRENIA; BRAIN MORPHOLOGY; CORTEX; MRI; DEFICITS; DISORDER; PSYCHOSIS; DENSITY; SCALE AB Functional measures have consistently shown prefrontal abnormalities in schizophrenia. However, structural magnetic resonance imaging (MRI) findings of prefrontal volume reduction have been less consistent. In this study, we evaluated prefrontal gray matter volume in first episode [first hospitalized) patients diagnosed with schizophrenia, compared with first episode patients diagnosed with affective psychosis and normal comparison subjects, to determine the presence in and specificity of prefrontal abnormalities to schizophrenia. Prefrontal gray and white matter volumes were measured from first episode patients with schizophrenia (n = 17), and from gender- and parental socio-economic status-matched subjects with affective (mainly manic) psychosis (n = 17) and normal comparison subjects (n = 17), age-matched within a narrow age range (18-29 years). Total (left and right) prefrontal gray matter volume was significantly reduced in first episode schizophrenia compared with first episode affective psychosis and comparison subjects. Follow-up analyses indicated significant left prefrontal gray matter volume reduction and trend level reduction on the right. Schizophrenia patients showed 9.2% reduction on the left and 7.7% reduction on the right compared with comparison subjects. White matter volumes did not differ among groups. These data suggest that prefrontal cortical gray matter Volume reduction is selectively present at first hospitalization in schizophrenia but not affective psychosis. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton Div,Dept Psychiat 116A, Brockton, MA 02301 USA. Brockton VA Med Ctr, Dept Psychiat, Neurosci Lab, Clin Neurosci Div, Brockton, MA USA. McLean Hosp, Cognit Neurosci Lab, Brockton, MA USA. McLean Hosp, Brain Imaging Ctr, Brockton, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,MRI Div,Surg Planning Lab, Boston, MA USA. RP McCarley, RW (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton Div,Dept Psychiat 116A, 940 Belmont St, Brockton, MA 02301 USA. EM martha_shenton@hms.harvard.edu; robert_mccarley@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NCRR NIH HHS [P41 RR13218-01, 1R01 RR11747-01A]; NIMH NIH HHS [MH 01110, MH 40977, MH 50740, R01 MH040799] NR 41 TC 102 Z9 104 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2001 VL 11 IS 4 BP 374 EP 381 DI 10.1093/cercor/11.4.374 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 413BP UT WOS:000167590300009 PM 11278200 ER PT J AU Faraone, SV Doyle, AE AF Faraone, SV Doyle, AE TI The nature and heritability of attention-deficit/hyperactivity disorder SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID DEFICIT-HYPERACTIVITY DISORDER; CATECHOL-O-METHYLTRANSFERASE; DOPAMINE TRANSPORTER GENE; HAPLOTYPE RELATIVE RISK; LEARNING-DISABILITIES; FAMILIAL ASSOCIATION; TOURETTE-SYNDROME; BEHAVIOR PROBLEMS; MATERNAL SMOKING; MORPHOMETRIC ANALYSIS AB This article reviews family, twin, and adoption studies, along with segregation analyses and molecular genetic studies, suggesting that both genetic and environmental factors contribute to the etiology of ADHD. Findings also indicate that the genetic mechanisms that predispose individuals to ADHD are likely to be complex, and the literature on ADHD raises many questions regarding clinical and pathophysiologic heterogeneity of the disorder. Although there is no single pathophysiologic profile of ADHD, data do implicate dysfunction in the frontosubcortical pathways that control attention and motor behavior. Moreover, the effectiveness of stimulants, along with animal models of hyperactivity, point to catecholamine dysregulation as at least one source of ADHD brain dysfunction. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Inst Psychiat Epidemiol & Genet, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St,Warren 705, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [1-R01HD37694-01, R01HD37999-01]; NIMH NIH HHS [R01MH57934] NR 135 TC 177 Z9 179 U1 5 U2 27 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 APR PY 2001 VL 10 IS 2 BP 299 EP + PG 20 WC Psychiatry SC Psychiatry GA 431RB UT WOS:000168643400008 PM 11351800 ER PT J AU Ino, Y Betensky, RA Zlatescu, MC Sasaki, H Macdonald, DR Stemmer-Rachamimov, AO Ramsay, DA Cairncross, JG Louis, DN AF Ino, Y Betensky, RA Zlatescu, MC Sasaki, H Macdonald, DR Stemmer-Rachamimov, AO Ramsay, DA Cairncross, JG Louis, DN TI Molecular subtypes of anaplastic oligodendroglioma: Implications for patient management at diagnosis SO CLINICAL CANCER RESEARCH LA English DT Article ID RECURRENT MALIGNANT GLIOMA; BRAIN-TUMOR SPECIMENS; CHROMOSOME 1P; PHASE-II; 19Q; P53; ASTROCYTOMAS; SURVIVAL; OLIGOASTROCYTOMA; PREDICTORS AB Purpose: In a prior study of anaplastic oligodendrogliomas treated with chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome Ip correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic management was not uniform, loss of Ip did not identify all chemosensitive tumors, nor did all patients whose tumors harbor a Ip loss have long survival. Experimental Design: To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic oligodendrogliomas, we studied a larger, more homogeneous group of 50 patients with histologically defined anaplastic oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy, Results: We demonstrate that these tumors can be divided genetically into four therapeutically and prognostically relevant subgroups. Patients whose tumors have combined but isolated losses of Ip and 19q have marked and durable responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome Ip alterations also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking Ip loss can also be divided into two subgroups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsive, aggressive tumors that are clinically and genotypically similar to glioblastomas. Conclusions: These data raise the possibility, for the first time, that therapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic oligodendroglioma. C1 London Reg Canc Ctr, London, ON N6A 4L6, Canada. Univ Western Ontario, Dept Clin Neurol Sci, London, ON N6A 4L6, Canada. Univ Western Ontario, Dept Oncol, London, ON N6A 4L6, Canada. Univ Western Ontario, Dept Pathol, London, ON N6A 4L6, Canada. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Cairncross, JG (reprint author), London Reg Canc Ctr, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. FU NCI NIH HHS [CA57683]; PHS HHS [MRC-MOP-37849] NR 30 TC 320 Z9 333 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2001 VL 7 IS 4 BP 839 EP 845 PG 7 WC Oncology SC Oncology GA 425NR UT WOS:000168297800013 PM 11309331 ER PT J AU Stern, JW Fang, JJ Shusterman, S Pierson, G Barr, R Pawel, B Diller, L Grupp, SA AF Stern, JW Fang, JJ Shusterman, S Pierson, G Barr, R Pawel, B Diller, L Grupp, SA TI Angiogenesis inhibitor TNP-470 during bone marrow transplant: Safety in a preclinical model SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-RISK NEUROBLASTOMA; TUMOR-GROWTH; ANTIANGIOGENIC THERAPY; RAPID-SEQUENCE; CANCER; CHILDREN AB High-dose therapy with stem cell rescue is a treatment option far patients with advanced solid tumors. Although this approach has promise for some pediatric cancers, especially neuroblastoma, it is limited by the risk of relapse posttransplant as well as concern about possible reinfused tumor cells in autologous stem cell products. Antiangiogenic agents given during and after recovery from high-dose therapy with stem cell rescue may decrease the risk of relapse. TNP-470 is an antiangiogenic agent now in clinical trials, Although it inhibits the growth of bone marrow (BM) colony-forming cells in vitro, no significant hematological toxicity has been seen in Phase I trials. To assess the feasibility of using antiangiogenic agents during the period of posttransplant hematapoietic engraftment, we have developed a model of stem cell transplant in mice. Mice mere lethally irradiated and then rescued with stem cells containing a transgene expressed in the hematopoietic lineage, Mice were then treated with TNP-470 or placebo, and assessed for survival, successful engraftment, and kinetics of engraftment, Both treated and control mice demonstrated reliable multilineage engraftment as well as normal lymphoid maturation with no excess mortality in the treated group. WBCs were lower but still within the normal range at d+28 in mice treated with bolus TNP-470, but not in those treated with continuous infusion TNP-470, compared with controls, These data indicate that inhibitors of angiogenesis do not adversely impact engraftment after stem cell transplantation. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat,Div Oncol, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat,Div Pathol, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Brighton, MA 02135 USA. RP Grupp, SA (reprint author), Childrens Hosp Philadelphia, ARC 902, 3516 Civic Ctr Blvd, Philadelphia, PA 19104 USA. RI Pawel, Bruce/G-5466-2011 NR 25 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2001 VL 7 IS 4 BP 1026 EP 1032 PG 7 WC Oncology SC Oncology GA 425NR UT WOS:000168297800036 PM 11309354 ER PT J AU Salem, RO Refaai, MA Cluette-Brown, JE Russo, JW Laposata, M AF Salem, RO Refaai, MA Cluette-Brown, JE Russo, JW Laposata, M TI Fatty acid ethyl esters in liver and adipose tissues as postmortem markers for ethanol intake SO CLINICAL CHEMISTRY LA English DT Article ID METABOLISM; MICROSOMES; SERUM AB Background: Fatty acid ethyl esters (FAEEs) are nonoxidative:metabolites of ethanol. FAEEs are found in liver, pancreas and adipose tissues up to 24 h after consumption of ethanol, and on that basis, they are potentially useful markers for ethanol intake. In this study with rats, we investigated the efficacy of using FAEEs in liver and in adipose tissue as postmortem markers for premortem ethanol ingestion. Methods: An animal study was conducted in which test rats received injections of ethanol and control rats received injections of normal saline. The rats were killed 2 h after the injections. The bodies of the animals were stored at 4 degreesC up to 12 h, and samples of liver and adipose tissues were collected at different time intervals and processed for FAEE quantification. In another set of experiments, the rats received injections and were killed as described above,:but bodies of animals from both groups were stored at 4, 25, or 37 degreesC;for up to 72 h, and liver samples were;collected and processed for FAEE quantification. Results: FAEEs were detected up to 12 h after death in liver-and adipose tissue samples from the bodies of ethanol-treated animals stored at 4 degreesC; negligible amounts. were detected in the bodies of animals that received normal saline. Adipose tissues contained higher amounts of FAEEs than liver, as well as more species. eight FAEE species in adipose tissue and five in liver tissue. Higher concentrations of FAEEs were detected in livers of treated animals stored at 25 degreesC for up to 48 h than in livers of controls stored under the same Conditions. Conclusions: For at least 12 h after death, FAEEs in liver and adipose tissues are useful postmortem markers of premortem ethanol ingestion. (C) 2001 American Association for Clinical Chemistry. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Room 235,Gray Bldg, Boston, MA 02114 USA. NR 20 TC 20 Z9 22 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2001 VL 47 IS 4 BP 722 EP 725 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 417QZ UT WOS:000167846800015 PM 11274023 ER PT J AU Wang, VJ Kuppermann, N Malley, R Barnett, ED Meissner, HC Schmidt, EV Fleisher, GR AF Wang, VJ Kuppermann, N Malley, R Barnett, ED Meissner, HC Schmidt, EV Fleisher, GR TI Meningococcal disease among children who live in a large metropolitan area, 1981-1996 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; NEISSERIA-MENINGITIDIS; EPIDEMIOLOGY; INFECTIONS; PNEUMONIA; PREVENTION; VACCINES AB Neisseria meningitidis is an important cause of serious bacterial infections in children. We undertook a study to identify meningococcal infections of the blood, cerebrospinal fluid, or both of children in a defined geographic area to describe the burden of disease and the spectrum of illness. We reviewed the medical records of all children aged <18 years who had meningococcal infections at the 4 pediatric referral hospitals in Boston, Massachusetts, from 1981 through 1996. We identified 231 patients with meningococcal disease; of these 231 patients, 194 (84%) had overt disease and 37 (16%) had unsuspected disease. Clinical manifestations included meningitis in 150 patients, hypotension in 26, and purpura in 17. Sixteen patients (7%) died. Although meningococcal disease is devastating to a small number of children, we found that the burden of pediatric disease that it caused at the 4 pediatric referral centers in this geographic region was limited; that patients with overt meningococcal disease are most likely to have meningitis; and that individual practitioners are unlikely to encounter a patient with unsuspected meningococcal disease. C1 Childrens Hosp Los Angeles, Div Emergency & Transport Med, Dept Pediat, Los Angeles, CA 90027 USA. Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA. Univ Calif Davis, Dept Internal Med, Div Emergency Med, Davis, CA 95616 USA. Massachusetts Gen Hosp, Dept Pediat, Div Infect Dis, Boston, MA 02114 USA. New England Med Ctr, Dept Pediat, Div Infect Dis, Boston, MA 02111 USA. Boston Med Ctr, Dept Pediat, Boston, MA USA. Boston Med Ctr, Maxwell Finland Lab Infect Dis, Boston, MA USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Wang, VJ (reprint author), Childrens Hosp Los Angeles, Div Emergency & Transport Med, Dept Pediat, 4650 Sunset Blvd, Los Angeles, CA 90027 USA. NR 28 TC 17 Z9 18 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2001 VL 32 IS 7 BP 1004 EP 1009 DI 10.1086/319595 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 414EY UT WOS:000167654100002 PM 11264027 ER PT J AU Klietmann, WF Ruoff, KL AF Klietmann, WF Ruoff, KL TI Bioterrorism: Implications for the clinical microbiologist SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID PUBLIC-HEALTH INFRASTRUCTURE; BIOLOGICAL WARFARE; CASE-HISTORY; SMALLPOX; ANTHRAX; THREAT; PREVENTION; TERRORISM; WEAPONS; MISIDENTIFICATION AB The specter of bioterrorism has captured the attention of government and military officials, scientists, and the general public. Compared to other sectors of the population clinical microbiologists are more directly impacted by concerns about bioterrorism. This review focuses on the role envisioned for clinical laboratories in response to a bioterrorist event. The microbiology and clinical aspects of the biological agents thought to be the mast likely tools of bioterrorists are presented. The historical background of the problem of bioterrorism and an overview of current U.S. preparedness planning, with an emphasis on the tales of health care professionals, are also included. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Microbiol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ruoff, KL (reprint author), Massachusetts Gen Hosp, Dept Pathol, GRB526,Fruit St, Boston, MA 02114 USA. NR 55 TC 86 Z9 94 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD APR PY 2001 VL 14 IS 2 BP 364 EP + DI 10.1128/CMR.14.2.364-381.2001 PG 19 WC Microbiology SC Microbiology GA 421DV UT WOS:000168047600007 PM 11292643 ER PT J AU Hazan, EJ Hornicek, FJ Tomford, W Gebhardt, MC Mankin, HJ AF Hazan, EJ Hornicek, FJ Tomford, W Gebhardt, MC Mankin, HJ TI The effect of adjuvant chemotherapy on osteoarticular allografts SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID BANKING; BONE AB Two hundred lower extremity osteoarticular allografts (in 200 patients) performed for aggressive or malignant bone tumors between 1976 and 1997 included 124 grafts of the distal femur, 36 of the proximal tibia, and 30 of the proximal femur. Seventy-four patients did not receive chemotherapy, and 126 received either adjuvant or neoadjuvant therapy. The diagnoses, mean ages, and length of followup were different for the two groups because most of the patients in the chemotherapy group had osteosarcoma, whereas the largest number in the control group had chondrosarcoma or parosteal osteosarcoma. The extent of the surgery was essentially the same for both patient groups, as is reflected by a low recurrence rate (7% for the control and 6% for the chemotherapy group), A statistical comparison of the various parameters showed that the infection, fracture, and amputation rates were the same, but the nonunion rate was markedly increased in the patients who received chemotherapy (32% versus 12%), Cox regression and Kaplan-Meier studies showed that chemotherapy had a significant effect on outcome, with the success rates for the two groups being quite different (72% versus 56%). The results for the distal femur showed a greater effect than for either the proximal tibia or the proximal femur. Analysis of these data suggest the distal femur is perhaps the most prone to healing problems, possibly based in part on the extent of the surgery, A final study supports the concept that the results improved in later years, suggesting a modification or application of the drugs used, better selection of patients, and improvements in surgical technique. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Gray 604, Boston, MA 02114 USA. NR 18 TC 34 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2001 IS 385 BP 176 EP 181 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 417PB UT WOS:000167842400028 PM 11302311 ER PT J AU Maher, MM McDermott, SR Fenlon, HM Conroy, D O'Keane, JC Carney, DN Stack, JP AF Maher, MM McDermott, SR Fenlon, HM Conroy, D O'Keane, JC Carney, DN Stack, JP TI Imaging of primary non-Hodgkin's lymphoma of the liver SO CLINICAL RADIOLOGY LA English DT Article DE lymphoma; liver; primary hepatic lymphoma; imaging; ultrasound; computed tomography; MRI ID PRIMARY HEPATIC LYMPHOMA; MALIGNANT-LYMPHOMA; VIRUS; MRI; CT AB AIM: To describe the radiological findings in primary liver lymphoma, which is a rare entity, presenting usually as a localized liver mass. MATERIALS AND METHODS: We reviewed retrospectively the imaging findings at presentation, of patients in whom a diagnosis of primary liver lymphoma was finally made histologically, The study period covered a 10-year period between January 1990 and December 1999, There were seven patients, all men, with a mean age of 49.6 years. Each patient presented with hepatobiliary disease without peripheral adenopathy, Imaging prior to diagnosis included ultrasonography (seven patients), computed tomography (seven patients) and magnetic resonance imaging (MRI) (two patients). Appearances during and after aggressive chemotherapy were reviewed. RESULTS: Imaging appearances were of either single or multiple Liver lesions simulating Liver metastases, On ultrasound all foci of primary hepatic lymphoma (PHL) were hypoechoic relative to normal liver. Computed tomography (CT) showed hypoattenuating lesions in all cases, and two cases showed rim enhancement following contrast administration. The MRI appearances were variable, and no pathognomonic feature of PHL was identified, so that histology was required in all patients to establish the diagnosis. CONCLUSIONS: This paper demonstrates the spectrum of findings encountered on various imaging modalities in PHL, We conclude that although PHL is a rare condition, it should always be considered in the differential diagnosis of liver metastases when no primary tumour is apparent. (C) 2001 The Royal College of Radiologists. C1 Mater Misericordiae Hosp, Dept Radiol, Dublin 7, Ireland. Mater Misericordiae Hosp, Dept Oncol, Dublin 7, Ireland. Mater Misericordiae Hosp, Dept Pathol, Dublin 7, Ireland. RP Maher, MM (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 17 TC 44 Z9 61 U1 0 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD APR PY 2001 VL 56 IS 4 BP 295 EP 301 DI 10.1053/crad.2000.0649 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 421GC UT WOS:000168055700007 PM 11286581 ER PT J AU Crowson, JJ Frueh, BC Snyder, CR AF Crowson, JJ Frueh, BC Snyder, CR TI Hostility and hope in combat-related posttraumatic stress disorder: A look back at combat as compared to today SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE hostility; hope; cognitions; posttraumatic stress disorder; military veterans; positive and negative affect ID AUTOMATIC THOUGHTS QUESTIONNAIRE; COMPENSATION-SEEKING STATUS; VIETNAM VETERANS; PSYCHOMETRIC PROPERTIES; PTSD; SCALE; VALIDATION; VALIDITY; SYMPTOMS; ANGER AB Thirty-seven male veterans with combat-related PTSD completed measures of hostile automatic thoughts, hope, nd positive and negative affect. Responses to the items of each measure were presented in two formats: (a) the veteran's feelings today and (b) (on a separate form) how he felt while in combat. Veterans reported significantly higher levels of hostility and negative affect in combat as opposed to today. Contrary to predictions, high levels of both positive affect and automatic positive thoughts also were reported in combat relative to today. Hope levels varied primarily as a function of being employed rather than unemployed. The implications and limitations of this methodology and these findings for combat veterans and other groups are discussed. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Crowson, JJ (reprint author), USN, Personnel Command, NPRST, PERS 13, 5720 Integr Dr, Millington, TN 38033 USA. NR 50 TC 13 Z9 13 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2001 VL 25 IS 2 BP 149 EP 165 DI 10.1023/A:1026439102180 PG 17 WC Psychology, Clinical SC Psychology GA 415LZ UT WOS:000167724200003 ER PT J AU Cruz, GD Galvis, DL Kim, M Le-Geros, RZ Barrow, SYL Tavares, M Bachiman, R AF Cruz, GD Galvis, DL Kim, M Le-Geros, RZ Barrow, SYL Tavares, M Bachiman, R TI Self-perceived oral health among three subgroups of Asian-Americans in New York City: a preliminary study SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE Asian-Americans; ethnicity; minorities; oral health; self-perceived oral health ID OLDER ADULTS; POPULATION; NEED; CARE AB Objectives: The aim of this preliminary study was to compare the perception of oral health among subgroups of Asian-American residents of New York City, USA. Methods: A close-ended questionnaire was administered to 255 Chinese, 134 Indian and 84 Pakistani adults, aged 18-65 years, during 1994-95. A comprehensive dental and oral examination was also performed. The associations of demographic and oral health variables with perceived oral health were evaluated using multivariate ordinal regression models. Results: When data were analyzed in a multivariate context, only ethnicity and income were significant predictors of perceived oral health, after adjusting for DMFT. The within-group multivariate analysis of the three ethnic subgroups' results were as follows: Among the Chinese there were no significant predictors, only income was strongly suggestive; among the Indians, number of missing teeth and number of years in the USA were significant predictors; and within the Pakistani group, DMFT was the only significant predictor. Conclusions: Results suggest that there are ethnic differences in the perception of oral health status even after adjusting for clinical variables as well as for demographic variables in this particular group of Asian-American residents of New York City. Predictors associated with the perception of oral health are different for each ethnic group. When designing oral health promotion activities to diverse ethnic groups, the cultural characteristics of each subgroup should be considered. C1 NYU, Coll Dent, Minor Oral Hlth Res Ctr, New York, NY 10010 USA. NYU, Sch Med, Dept Environm Med, New York, NY USA. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Cruz, GD (reprint author), NYU, Coll Dent, Minor Oral Hlth Res Ctr, 345 E 24th St,Room 806, New York, NY 10010 USA. FU NIDCR NIH HHS [P20 DE10593] NR 32 TC 17 Z9 19 U1 1 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD APR PY 2001 VL 29 IS 2 BP 99 EP 106 DI 10.1034/j.1600-0528.2001.290204.x PG 8 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 410CE UT WOS:000167421800004 PM 11300178 ER PT J AU Chen, JN van Bebber, F Goldstein, AM Serluca, FC Jackson, D Childs, S Serbedzija, G Warren, KS Mably, JD Lindah, P Mayer, A Haffter, P Fishman, MC AF Chen, JN van Bebber, F Goldstein, AM Serluca, FC Jackson, D Childs, S Serbedzija, G Warren, KS Mably, JD Lindah, P Mayer, A Haffter, P Fishman, MC TI Genetic steps to organ laterality in zebrafish SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Article DE symmetry; heterotaxy; situs inversus; fork head gene ID LEFT-RIGHT ASYMMETRY; SITUS-INVERSUS; FORK-HEAD; EXPRESSION; VERTEBRATE; PATHWAYS; MUTATION; VISCERUM; PATTERN; LEFTY-1 AB All internal organs are asymmetric along the left-right axis. Here we report a genetic screen to discover mutations which perturb organ laterality. Our particular focus is upon whether, and how, organs are linked to each other as they achieve their laterally asymmetric positions. We generated mutations by ENU mutagenesis and examined F3 progeny using a cocktail of probes that reveal early primordia of heart, gut, liver and pancreas. From the 750 genomes examined, we isolated seven recessive mutations which affect the earliest left-right positioning of one or all of the organs. None of these mutations caused discernable defects elsewhere in the embryo at the stages examined. This is in contrast to those mutations we reported previously (Chen et al., 1997) which, along with left-right abnormalities, cause marked perturbation in gastrulation, body form or midline structures. We find that the mutations can be classified on the basis of whether they perturb relationships among organ laterality. In Class I mutations, none of the organs manifest any left-right asymmetry. The heart does not jog to the left and normally left-predominant BMP4 in the early heart tube remains symmetric. The gut tends to remain midline. There frequently is a remarkable bilateral duplication of liver and pancreas. Embryos with Class 2 mutations have organotypic asymmetry but, in any given embryo, organ positions can be normal, reversed or randomized. Class 3 reveals a hitherto unsuspected gene that selectively affects laterality of heart. We find that visceral organ positions are predicted by the direction of the preceding cardiac jog. We interpret this as suggesting that normally there is linkage between cardiac and visceral organ laterality. Class I mutations, we suggest, effectively remove the global laterality signals, with the consequence that organ positions are effectively symmetrical. Embryos with Class 2 mutations do manifest linkage among organs, but it may be reversed, suggesting that the global signals may be present but incorrectly orientated in some of the embryos. That laterality decisions of organs may be independently perturbed, as in the Class 3 mutation, indicates that there are distinctive pathways for reception and organotypic interpretation of the global signals. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Max Planck Inst Entwicklungsbiol, Genet Abt, D-72076 Tubingen, Germany. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM fishman@cvrc.mgh.harvard.edu OI Chen, Jau-Nian/0000-0001-8807-3607 NR 28 TC 37 Z9 37 U1 1 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PD APR PY 2001 VL 2 IS 2 BP 60 EP 68 DI 10.1002/cfg.74 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 485RL UT WOS:000171771300002 PM 18628903 ER PT J AU Smeaton, LM DeGruttola, V Robbins, GK Shafer, RW AF Smeaton, LM DeGruttola, V Robbins, GK Shafer, RW TI ACTG (AIDS Clinical Trials Group) 384: A strategy trial comparing consecutive treatments for HIV-1 SO CONTROLLED CLINICAL TRIALS LA English DT Article DE clinical trials design; phase III study; randomized; controlled; multicenter; double-blind; trial; AIDS ID IMMUNODEFICIENCY-VIRUS INFECTION; PROTEASE INHIBITORS; ANTIRETROVIRAL THERAPY; DRUG-RESISTANCE; PLUS INDINAVIR; DOUBLE-BLIND; ZIDOVUDINE; LAMIVUDINE; DIDANOSINE; MUTATIONS AB ACTG (AIDS Clinical Trials Group) 384 is designed to evaluate different strategies for antiretroviral treatment in HIV-1-infected individuals with no previous exposure to antiretroviral treatment. The study is a randomized, partially double-blinded, controlled trial with 980 subjects at 81 centers in the United States and Italy. The study has a factorial design that addresses the following scientific questions: (1) Does the best initial choice of therapy include both a protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) in a four-drug combination with nucleoside analogue (NRTI) drugs, or should these agents be used sequentially in three-drug combinations?; (2) Which sequence is best in a three-drug regimen-PI followed by NNRTI or NNRTI followed by PI ?; (3) Which is the best sequence of dual NRTI combinations-zidovudine plus lamivudine followed by didanosine plus stavudine, or the converse? Subjects in the three-drug combination arms are offered a salvage regimen after failure of their second regimen; subjects in the four-drug combination arm are offered a salvage regimen after failure of their first regimen. The primary endpoint of the study is the time until salvage; secondary endpoints include time to virological failure and time to toxicity related discontinuation of therapy. A Division of AIDS Data and Safety Monitoring Board will review the trial for safety and efficacy. (C) Elsevier Science Inc. 2001. C1 Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Smeaton, LM (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 651 Huntington Ave,Francois-Xavier Bagnound Bldg, Boston, MA 02115 USA. RI Robbins, Gregory/F-7988-2011 FU NIAID NIH HHS [U01 AI038858, U01 AI038855, R01 AI046148, AI-38855, AI-38858] NR 30 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD APR PY 2001 VL 22 IS 2 BP 142 EP 159 DI 10.1016/S0197-2456(00)00126-4 PG 18 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 421TE UT WOS:000168079000007 PM 11306153 ER PT J AU McCowen, KC Ling, PR Ciccarone, A Mao, YL Chow, JC Bistrian, BR Smith, RJ AF McCowen, KC Ling, PR Ciccarone, A Mao, YL Chow, JC Bistrian, BR Smith, RJ TI Sustained endotoxemia leads to marked down-regulation of early steps in the insulin-signaling cascade SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Parenteral-and-Enteral-Nutrition CY JAN, 1998 CL ORLANDO, FLORIDA SP Amer Soc Parenter & Enter DE catabolic stress; endotoxin; endotoxin tolerance; insulin receptor; insulin resistance; insulin signaling; insulin receptor substrate proteins; malnutrition; phosphatidylinositide 3-kinase; tyrosine phosphorylation ID TUMOR-NECROSIS-FACTOR; SKELETAL-MUSCLE; RECEPTOR SUBSTRATE-1; GLUCOSE-UPTAKE; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; TYROSINE PHOSPHORYLATION; RESISTANCE; TOLERANCE; RATS AB Objectives: To determine the effects of sustained, 3-day endotoxin infusion on early steps of the insulin-signaling pathway in rat liver and skeletal muscle in vivo; to examine insulin signaling in well-established acute endotoxin models of insulin resistance. Design: Prospective, controlled animal study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats: 24 in the 3-day endotoxin study, 22 in each acute endotoxin study, Interventions: In prolonged endotoxemia studies, endotoxin (1 mg.kg(-1).24 hrs(-1)) was administered via jugular venous catheter for 74 hrs, Insulin was then injected, and liver and skeletal muscle were removed after 5 mins, In acute endotoxemia studies, an endotoxin bolus (1 mg/kg) was administered, and insulin-signaling responses were studied after 4 hrs, Measurements and Main Results:ln liver of rats with sustained endotoxemia, there were significant decreases in insulin-stimulated tyrosine phosphorylation of insulin receptors (74%), insulin receptor substrate (IRS)-1 (74%), and IRS2 (53%); binding of the p85 subunit of phosphatidylinositide 3-kinase to IRS1 (80%); and IRS1-precipitable phosphatidylinositide 3-kinase activity (>90%). These findings were associated with significant reductions in abundance of insulin receptors (37%), IRS1 (60%), and IRS2 (23%). Signaling in skeletal muscle was similarly affected, with reduced IRS1 phosphorylation (49%), IRS1 abundance (50%), and binding of p85 to IRS1 (57%). Insulin signaling 4 hrs after endotoxin administration was not different from controls. Conclusions: Prolonged endotoxemia is associated with marked deficits in early steps of the insulin-signaling pathway, which are at least partly explained by reduced abundance of the insulin receptor and IRS proteins. Signaling defects were not evident 4 hrs after endotoxin administration under conditions of adequate nutrition, indicating that insulin resistance develops gradually, may require concomitant malnutrition, and is not reversed by the development of endotoxin tolerance. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Smith, RJ (reprint author), Rhode Isl Hosp, Browr Med Sch, Div Endocrinol, 593 Eddy St, Providence, RI 02903 USA. FU NIDDK NIH HHS [DK-43038, DK-50411] NR 39 TC 27 Z9 28 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2001 VL 29 IS 4 BP 839 EP 846 DI 10.1097/00003246-200104000-00032 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 421KN UT WOS:000168063700022 PM 11373480 ER PT J AU Okamura, H Rao, A AF Okamura, H Rao, A TI Transcriptional regulation in lymphocytes SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID KAPPA-B ACTIVATION; KINASE C-THETA; CYTOKINE GENE-EXPRESSION; T-CELL DIFFERENTIATION; HISTONE ACETYLATION; V(D)J RECOMBINATION; NUCLEOSOMAL DNA; FACTOR GATA-3; FACTOR NFAT1; TH1 CELLS AB Lymphocytes have been used to investigate many cellular processes, including lineage commitment, differentiation, proliferation and apoptosis. The transcription factors that mediate these processes are often expressed broadly in many cell types. The emerging theme is one of cell-type-specific regulation, affecting not only the functional activation of transcription factors but also their access to appropriate regions of DNA. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Okamura, H (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA72320-04, CA42471]; NIAID NIH HHS [AI44432, AI40127] NR 55 TC 17 Z9 17 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 2001 VL 13 IS 2 BP 239 EP 243 DI 10.1016/S0955-0674(00)00203-9 PG 5 WC Cell Biology SC Cell Biology GA 413NT UT WOS:000167619200017 PM 11248559 ER PT J AU Dale, AM Halgren, E AF Dale, AM Halgren, E TI Spatiotemporal mapping of brain activity by integration of multiple imaging modalities SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID EVENT-RELATED FMRI; HUMAN VISUAL-CORTEX; DEPTH-RECORDED POTENTIALS; FUNCTIONAL MRI; CORTICAL ACTIVITY; RETINOTOPIC ORGANIZATION; SENSORY STIMULATION; OCCIPITAL CORTEX; AUDITORY ODDBALL; LIGHT-SCATTERING AB Functional magnetic resonance imaging (fMRI) and positron emission tomography measure local changes in brain hemodynamics induced by cognitive or perceptual tasks. These measures have a uniformly high spatial resolution of millimeters or less, but poor temporal resolution (about 1 s). Conversely, electroencephalography (EEG) and magnetoencephalography (MEG) measure instantaneously the current flows induced by synaptic activity, but the accurate localization of these current flows based on EEG and MEG data alone remains an unsolved problem. Recently, techniques have been developed that, in the context of brain anatomy visualized with structural MRI, use both hemodynamic and electromagnetic measures to arrive at estimates of brain activation with high spatial and temporal resolution. These methods range from simple juxtaposition to simultaneous integrated techniques. Their application has already led to advances in our understanding of the neural bases of perception, attention, memory and language. Further advances in multi-modality integration will require an improved understanding of the coupling between the physiological phenomena underlying the different signal modalities. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Dale, AM (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, 149 13th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [R01-RR13609, P41-RR14075]; NINDS NIH HHS [R01-NS18741, R01-NS39581] NR 82 TC 205 Z9 207 U1 3 U2 21 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2001 VL 11 IS 2 BP 202 EP 208 DI 10.1016/S0959-4388(00)00197-5 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 429FN UT WOS:000168505500009 PM 11301240 ER PT J AU Caviness, VS AF Caviness, VS TI Research strategies in autism: a story with two sides SO CURRENT OPINION IN NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Caviness, VS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2001 VL 14 IS 2 BP 141 EP 143 DI 10.1097/00019052-200104000-00001 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 430GA UT WOS:000168565100001 PM 11262726 ER PT J AU Mochida, GH Walsh, CA AF Mochida, GH Walsh, CA TI Molecular genetics of human microcephaly SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID LINKED MENTAL-RETARDATION; SIMPLIFIED GYRAL PATTERN; NIJMEGEN BREAKAGE SYNDROME; VARIABLY SHORT STATURE; MUTATIONAL SPECTRUM; RETT-SYNDROME; MAPS; DNA; PROTEIN; LOCUS AB Human microcephaly comprises a heterogeneous group of conditions that are characterized by a failure of normal brain growth. Microcephaly can be caused by many injurious or degenerative conditions, or by developmental malformations in which the growth of the brain is impaired as a result of defects in pattern formation, cell proliferation, cell survival, cell differentiation, or cell growth. These latter forms of congenital microcephaly are frequently inherited, usually as recessive traits, and are associated with mental retardation and sometimes epilepsy, Some of the genes that cause congenital microcephaly are likely to control crucial aspects of neural development, and may also be involved in the evolutionary explosion of cortical size that characterizes primates. There has recently been a rapid advance in the use of genetic mapping techniques to identify genetic loci responsible for microcephaly, Although several loci have been mapped, the condition is clearly genetically and clinically heterogeneous, curt Opin Neurol 14:151-156 (C) 2001 Lippincott Williams & Wilkins. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Div Neurogenet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Clin Investigator Training Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. RP Walsh, CA (reprint author), Beth Israel Deaconess Med Ctr, Harvard Inst Med, Dept Neurol, Room 816,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NINDS NIH HHS [R01 NS 32457, R01 NS 35129] NR 40 TC 114 Z9 116 U1 7 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2001 VL 14 IS 2 BP 151 EP 156 DI 10.1097/00019052-200104000-00003 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 430GA UT WOS:000168565100003 PM 11262728 ER PT J AU MacCollin, M Kwiatkowski, D AF MacCollin, M Kwiatkowski, D TI Molecular genetic aspects of the phakomatoses: tuberous sclerosis complex and neurofibromatosis 1 SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID GERM-LINE MOSAICISM; NF1 GENE; TSC2 GENE; MUTATIONAL SPECTRUM; SOMATIC MUTATION; SPLICING DEFECTS; EKER RAT; TYPE-1; HAMARTIN; IDENTIFICATION AB The phakomatoses are a diverse group of diseases characterized by skin lesions in early childhood followed by the development of tumors in many other organs. Tuberous sclerosis complex and neurofibromatosis 1 are of special interest to the neurologist because of their prominent neuro-oncological and neuro-developmental consequences. The cloning of genes responsible for these two diseases has led to the identification of causative mutations. an understanding of basic cellular pathophysiology and the development of animal models. Current laboratory investigations are focused on bringing clinical relevance to these findings, including the prospects of molecular diagnostics and rational therapeutics. Curr Opin Neurol 14:163-169. (C) 2001 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Neurol Serv, Charlestown, MA USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP MacCollin, M (reprint author), Massachusetts Gen Hosp E, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS35878, NS31535] NR 50 TC 12 Z9 13 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2001 VL 14 IS 2 BP 163 EP 169 DI 10.1097/00019052-200104000-00005 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 430GA UT WOS:000168565100005 PM 11262730 ER PT J AU Selkin, B Rajadhyaksha, M Gonzalez, S Langley, RG AF Selkin, B Rajadhyaksha, M Gonzalez, S Langley, RG TI In vivo confocal microscopy in dermatology SO DERMATOLOGIC CLINICS LA English DT Article ID SCANNING LASER MICROSCOPY; IN-VIVO; HUMAN SKIN; EPILUMINESCENCE MICROSCOPY; ROUTINE HISTOLOGY; CONTRAST; LESIONS AB Confocal microscopy is an optical imaging tool that allows for high resolution, noninvasive imaging in vivo. Thin sections of human tissue can be imaged allowing visualization of cellular and nuclear detail without biopsy. This technique recently has been used to image benign and malignant pigmented skin lesions, nonmelanoma skin cancer, inflammatory skin conditions, and dynamic skin processes. C1 Dalhousie Univ, Dept Med, Div Dermatol, Halifax, NS B3H 2Y6, Canada. Albany Med Ctr, Albany, NY USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Wellman Lab, Boston, MA 02114 USA. RP Langley, RG (reprint author), Dalhousie Univ, Dept Med, Div Dermatol, Dickson Bldg,Room 4-195,1278 Tower Rd, Halifax, NS B3H 2Y6, Canada. NR 25 TC 32 Z9 33 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD APR PY 2001 VL 19 IS 2 BP 369 EP + DI 10.1016/S0733-8635(05)70274-6 PG 11 WC Dermatology SC Dermatology GA 468HD UT WOS:000170751300013 PM 11556245 ER PT J AU Khatri, KA AF Khatri, KA TI The effects of variable pulse width of Er : YAG laser on facial skin SO DERMATOLOGIC SURGERY LA English DT Article ID ERBIUM-YAG; RHYTIDES AB BACKGROUND. The use of CO2 and Er:YAG lasers for resurfacing has increased significantly in the past few years. Er:YAG laser causes pinpoint bleeding during and after treatment with a typical pulse width of 250 mu sec. A longer pulse of Er:YAG laser can potentially coagulate dermal blood vessels and increase the residual thermal damage (RTD). OBJECTIVE. To evaluate the effects of various pulse durations of Er,YAG laser on the depth of RTD and bleeding. METHODS. The preauricular skin of a volunteer was exposed to Er:YAG laser at 250-, 350-, and 700-mu sec pulse durations, with a fluence of 5 J/cm(2). The number of passes varied between 6 and 16. The treated skin was excised and a histologic evaluation was done. RESULTS. The maximum depth of RTD was 50 mum and there was decreased bleeding with a 700-mu sec pulse duration. CONCLUSION. The increased pulse duration of Er:YAG laser of 700 mus does not increase the maximum reported RTD and therefore would not change the recovery time and may have a beneficial effect on hemostasis. C1 Skin & Laser Surg Ctr New England, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Khatri, KA (reprint author), Skin & Laser Surg Ctr New England, 777 Concord Ave,Suite 206, Cambridge, MA 02138 USA. NR 6 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD APR PY 2001 VL 27 IS 4 BP 332 EP 334 DI 10.1046/j.1524-4725.2001.00111.x PG 3 WC Dermatology; Surgery SC Dermatology; Surgery GA 420HL UT WOS:000167999500002 PM 11298701 ER PT J AU Snow, S Madjar, DD Hardy, S Bentz, M Lucarelli, MJ Bechard, R Aughenbaugh, W McFadden, T Sharata, H Dudley, C Landeck, A AF Snow, S Madjar, DD Hardy, S Bentz, M Lucarelli, MJ Bechard, R Aughenbaugh, W McFadden, T Sharata, H Dudley, C Landeck, A TI Microcystic adnexal carcinoma: Report of 13 cases and review of the literature SO DERMATOLOGIC SURGERY LA English DT Review ID SWEAT GLAND CARCINOMA; MOHS MICROGRAPHIC SURGERY; DUCT CARCINOMA; FOLLOW-UP; DIFFERENTIATION; INVASION; SKIN; LIP; EXCISION; NEOPLASM AB BACKGROUND. Microcystic adnexal carcinoma (MAC) is a rare tumor of the skin. Clinically it often masquerades as a firm, subcutaneous nodule on the head and neck regions. Microscopically it extends far beyond assessed clinical margins spreading locally in the dermal, subcutaneous, and perineural tissue planes. The local recurrence rate by standard excision is about 50%. Recent preliminary reports indicate more favorable cure rates with Mohs micrographic surgery (MMS). OBJECTIVE. TO present our data on 13 cases (12 patients) of MAC treated by MMS. In addition, we reviewed the medical literature to summarize the accumulated experience of MMS treatment in the management of MAC. We also present a case of bilateral MAC of the face and describe a renal transplant recipient on immunosuppressive therapy who developed MAC of the nasal bridge. METHODS. We reviewed and updated our series of MAC cases treated by MMS over the last 9 years. A total of 13 cases of MAC are reviewed. We also searched the literature for MAC treated by MMS with a follow-up of more than 2-years. RESULTS. One patient had bilateral MAC of the nose and cheek. Another patient developed a MAC of the nasal bridge 20 years after renal transplantation. In this patient predisposing factors were radiation for teenage acne and immunosuppression therapy. A total of 13 cases of MAC were treated by MMS with no recurrences, with a mean follow-up of 5.0 years (range 1.1-8.0 years). CONCLUSION. We update the medical literature with 13 MAC cases treated by MMS. To our knowledge there have been 148 cases of MAC reported in the world literature. Including our series, there have been 73 cases of MAC treated with MMS. There were only four treatment failures. Regional and/or distant metastasis from MAC is rare, with only one reported death. Following MMS, the 2-year success rate was 89.7% (35 of 39). The accumulated data continue to confirm that when MAC is discovered early and is readily accessible to excision by MMS and other subspecialty support, a favorable outcome can be expected. C1 Univ Wisconsin, Sch Med, Dept Surg, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Ophthalmol, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Hosp, Div Dermatol, Madison, WI USA. RP Snow, S (reprint author), Mohs Clin, 2880 Univ Ave, Madison, WI 53705 USA. NR 54 TC 61 Z9 62 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD APR PY 2001 VL 27 IS 4 BP 401 EP 408 DI 10.1046/j.1524-4725.2001.00208.x PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 420HL UT WOS:000167999500017 PM 11298716 ER PT J AU Lorenzen, JA Baker, SE Denhez, F Melnick, MB Brower, DL Perkins, LA AF Lorenzen, JA Baker, SE Denhez, F Melnick, MB Brower, DL Perkins, LA TI Nuclear import of activated D-ERK by DIM-7, an importin family member encoded by the gene moleskin SO DEVELOPMENT LA English DT Article DE corkscrew; receptor tyrosine kinase signaling; importin superfamily; MAP kinase; nuclear transport; moleskin; Drosophila ID DROSOPHILA EGF RECEPTOR; TYROSINE-PHOSPHATASE CORKSCREW; SIGNAL-TRANSDUCTION PATHWAY; MAP KINASE KINASE; PROTEIN-KINASE; NEURONAL DIFFERENTIATION; WING MORPHOGENESIS; REGULATED KINASE; CELL-MIGRATION; PS INTEGRINS AB The initiation of gene expression in response to Drosophila receptor tyrosine kinase signaling requires the nuclear import of the MAP kinase, D-ERK. However, the molecular details of D-ERK translocation are largely unknown. In this regard, we have identified D-Importin-7 (DIM-7), the Drosophila homolog of vertebrate importin 7, and its gene moleskin, DIM-7 exhibits a dynamic nuclear localization pattern that overlaps the spatial and temporal profile of nuclear, activated D-ERK. Co-immunoprecipitation experiments show that DIM-7 associates with phosphorylated D-ERK in Drosophila S2 cells. Furthermore, moleskin mutations enhance hypomorphic and suppress hypermorphic D-ERK mutant phenotypes. Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7. Mutations in the Drosophila Importin beta homolog Ketel, also reduce the nuclear localization of activated D-ERK. Together, these data indicate that DIM-7 and Ketel are components of the nuclear import machinery for activated D-ERK. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA 02114 USA. Univ Arizona, Dept Biochem, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. RP Perkins, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA 02114 USA. FU NIGMS NIH HHS [5F32GM19149, 5F32GM17901-03] NR 63 TC 59 Z9 59 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 2001 VL 128 IS 8 BP 1403 EP 1414 PG 12 WC Developmental Biology SC Developmental Biology GA 429CR UT WOS:000168498900017 PM 11262240 ER PT J AU Cox, DJ Gonder-Frederick, L Polonsky, W Schlundt, D Kovatchev, B Clarke, W AF Cox, DJ Gonder-Frederick, L Polonsky, W Schlundt, D Kovatchev, B Clarke, W TI Blood glucose awareness training (BGAT-2) - Long-term benefits SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; HYPOGLYCEMIA; IDDM; IMPACT AB OBJECTIVE - Blued glucose awareness training (BGAT) has been shown to improve awareness of blood glucose (BG! fluctuations among adults with type 1 diabetes. This study investigates the long-term (12-month) benefits of BGAT-2. RESEARCH DESIGN AND METHODS - A total of 73 adults with type diabetes participated in a 6-month repeated baseline design with a 12-month follow up. At 6 months and 1 month before BGAT-2 and at 1, 6, and 12 months after BGAT-2, subjects used a handheld computer for 50 trials and completed psychological tests. Throughout assessment, subjects completed diaries, recording occurrences of diabetic ketoacidosis, severe hypoglycemia, and motor vehicle violations. During follow-up, 50% of the subjects received booster training. RESULTS - During the first and last halves of both the baseline period and the follow-up period, dependent variables were generally stable. However, from baseline to follow-up. BGAT-2 led to I) improved detection of hypoglycemia and hyperglycemia; 2) improved judgment regarding when to lower high DG, raise low BG. and not drive while hypoglycemic; 3) reduction in occurrence of diabetic ketoacidosis, severe hypoglycemia. and motor vehicle violations; and 4) improvement in terms of worry about hypoglycemia, quality of life. and diabetes knowledge. Reduction in severe hypoglycemia was not associated with a worsening of metabolic control (HbA(t)). The presence or absence of booster training did not differentially affect these benefits. CONCLUSION - BGAT has sustained broad-ranging benefits, independent of booster Intervention. C1 Univ Virginia, Hlth Sci Ctr, Behav Med Ctr, Charlottesville, VA 22908 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Vanderbilt Univ, Dept Psychol, Nashville, TN USA. RP Cox, DJ (reprint author), Univ Virginia, Hlth Sci Ctr, Behav Med Ctr, Box 223, Charlottesville, VA 22908 USA. FU NIDDK NIH HHS [DK20579, DK27085, DK28288] NR 19 TC 106 Z9 111 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2001 VL 24 IS 4 BP 637 EP 642 DI 10.2337/diacare.24.4.637 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 415BX UT WOS:000167701600007 PM 11315822 ER PT J AU Barzilay, JI Jones, CL Davis, BR Basile, JN Goff, DC Ciocon, JO Sweeney, ME Randall, OS AF Barzilay, JI Jones, CL Davis, BR Basile, JN Goff, DC Ciocon, JO Sweeney, ME Randall, OS CA ALLHAT Collaborative Res Grp TI Baseline characteristics of the diabetic participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO DIABETES CARE LA English DT Article ID CORONARY-ARTERY DISEASE; CARDIOVASCULAR EVENTS; RANDOMIZED TRIAL; SYSTOLIC HYPERTENSION; CONVENTIONAL THERAPY; CALCIUM-ANTAGONISTS; RISK; INSULIN; HEALTH; MORTALITY AB Objective - Hypertension (HTN) is a major risk factor for cardiovascular disease (CVD) in the setting of diabetes. There is no consensus on how best to treat hypertension among those with diabetes. Here we describe the characteristics of a cohort of hypertensive adults with diabetes who are part of a large prospective blood pressure study. This study will help clarify the treatment of HTN in the setting of diabetes. Research design and methods - The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (AI.I.HAT) is a double-blind randomized trial of 42,448 high-risk hypertensive participants, ages greater than or equal to 55 years, designed to determine whether the incidence of fatal and nonfatal coronary heart disease (CHD) and combined cardiovascular events (fatal and nonfatal CHD, revascularization surgery, angina pectoris, congestive heart failure, and stroke) differs between diuretic (chlorthahdone) treatment and three alternative antihypertensive therapies: a calcium channel blocker (amlodipine), an ACE inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). The planned follow-up is an average of 6 years, to be completed in March 2002. Results - There are 15,297 diabetic individuals in the ALLHAT study (36.0% of the entire cohort). Of these individuals, 50.2% are male, 39.4% are African-American, and 17.7% are Hispanic. Demographic and laboratory characteristics of the cohort are similar to those of other studies of the U.S. elderly population with HTN. The sample size has 42 and 93% confidence respectively, for detecting a 16% difference between the diuretic and each of the nondiuretic treatments for the two study outcomes. Conclusions - The diabetic cohort in ALLHAT will be able to provide valuable information about the treatment of hypertension in older diabetic patients at risk for incident CVD. C1 Kaiser Permanente, Div Endocrinol, Tucker, GA 30084 USA. Univ Texas, Sch Publ Hlth, Dept Biometry, Houston, TX USA. Ralph H Johnson Vet Adm Med Ctr, Dept Med, Charleston, SC USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Cleveland Clin, Dept Geriatr Med, Ft Lauderdale, FL USA. Atlanta VA Med Ctr, Dept Hypertens & Lipid Metab, Atlanta, GA USA. Howard Univ, Div Cardiovasc Dis, Washington, DC 20059 USA. RP Barzilay, JI (reprint author), Kaiser Permanente, Div Endocrinol, 200 Crescent Ctr, Tucker, GA 30084 USA. NR 44 TC 14 Z9 17 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2001 VL 24 IS 4 BP 654 EP 658 DI 10.2337/diacare.24.4.654 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 415BX UT WOS:000167701600011 PM 11315826 ER PT J AU Chaturvedi, N Fuller, JH Pokras, F Rottiers, R Papazoglou, N Aiello, LP AF Chaturvedi, N Fuller, JH Pokras, F Rottiers, R Papazoglou, N Aiello, LP CA EUCLID Study Grp TI Circulating plasma vascular endothelial growth factor and microvascular complications of Type 1 diabetes mellitus: the influence of ACE inhibition SO DIABETIC MEDICINE LA English DT Article DE ACE inhibitors; retinopathy; Type 1 diabetes mellitus; VEGF ID EURODIAB IDDM COMPLICATIONS; FACTOR VEGF; RETINAL NEOVASCULARIZATION; SERUM LEVELS; RETINOPATHY; PERMEABILITY; CELLS; ADOLESCENTS; EXPRESSION; PLATELETS AB Aims To determine whether circulating plasma vascular endothelial growth factor (VEGF) is elevated in the presence of diabetic microvascular complications, and whether the impact of angiotensin-converting enzyme (ACE) inhibitors on these complications can be accounted for by changes in circulating VEGF. Methods Samples (299/354 of those with retinal photographs) from the EUCLID placebo-controlled clinical trial of the ACE inhibitor lisinopril in mainly normoalbuminuric non-hypertensive Type 1 diabetic patients were used. Albumin excretion rate (AER) was measured 6 monthly. Geometric mean VEGF levels by baseline retinopathy status, change in retinopathy over 2 years, and by treatment with lisinopril were calculated, Results No significant correlation was observed between VEGF at baseline and age, diabetes duration, glycaemic control, blood pressure, smoking, fibrinogen and von Willebrand factor. Mean VEGF concentration at baseline was 11.5 (95% confidence interval 6.0-27.9) pg/ml in those without retinopathy, 12.9 (6.0-38.9) pg/ml in those with non-proliferative retinopathy, and 16.1 (8.1-33.5) pg/ml in those with proliferative retinopathy (P = 0.06 for trend). Baseline VEGF was 15.2 pg/ml in those who progressed by at least one level of retinopathy by 2 years compared to 11.8 pg/ml in those who did not (P = 0.3). VEGF levels were not altered by lisinopril treatment. Results were similar for AER. Conclusions Circulating plasma VEGF concentration is not strongly correlated with risk factor status or microvascular disease in Type 1 diabetes, nor is it affected by ACE inhibition. Changes in circulating VEGF cannot account for the beneficial effect of ACE inhibition on retinopathy. C1 UCL, Dept Epidemiol & Publ Hlth, EURODIAB, London, England. Joslin Diabet Ctr, Sect Vasc Cell Biol, Boston, MA 02215 USA. Univ Ghent, Dept Endocrinol, B-9000 Ghent, Belgium. Agios Pavlos Gen Hosp, Diabet Unit, Thessaloniki, Greece. RP Chaturvedi, N (reprint author), St Marys Hosp, Imperial Coll Med, Dept Epidemiol & Publ Hlth, Norfolk Pl, London W2 1PG, England. EM n.chaturvedi@ic.ac.uk NR 38 TC 40 Z9 43 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD APR PY 2001 VL 18 IS 4 BP 288 EP 294 DI 10.1046/j.1464-5491.2001.00441.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 450QA UT WOS:000169753600006 PM 11437859 ER PT J AU Tambouret, R Bell, DA Centeno, BA AF Tambouret, R Bell, DA Centeno, BA TI Significance of histiocytes in cervical smears from peri/postmenopausal women SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE histiocytes; postmenopausal; perimenopausal; cervical smears; vaginal smears; endometrial neoplasia ID ENDOMETRIAL ADENOCARCINOMA AB Histiocytes in cervicovaginal smears from peri- or postmenopausal women have been viewed as a potential indicator of endometrial neoplasia, but recent studies have refuted that view. This study further defines the clinical significance of such findings. All cervical smears were selected from women (greater than or equal to 50 yr) in whom the presence of histiocytes was mentioned; pertinent clinical history, follow-up information, and selected slides were reviewed. Among 105,225 total cervicovaginal smears from a 3.5-yr period, 106 smears from 103 women were identified. Forty-two patients (41%) were on hormone replacement therapy (2 on tamoxifen), and 23 (22.3%) patients experienced vaginal bleeding, all of whom had biopsy or cytology follow-up. Ten (9.6%) patients had no follow-up, 35 (32%) had repeat smears only, and 58 (56.3%) had endometrial/endocervical sampling. In 28 patients, the index smear was categorized as other than within normal limits or benign cellular changes; of these, 24 had subsequent tissue sampling and 4 had cytology follow-up. Of the patients with tissue sampling, 51 (84%) had benign findings (including polyps), 2 (3.5%) had hyperplasia, and 5 (10%) had adenocarcinoma. All 5 patients with adenocarcinoma had endometrial glandular cells on the smear, and 4 had vaginal bleeding. One patient with hyperplasia had vaginal bleeding, and the other was on tamoxifen and had endometrial glandular cells on the smear. None of the patients having only histiocytes on their smears and no clinical symptoms or risk factors had endometrial adenocarcinoma or hyperplasia. These findings support the conclusion that the presence of histiocytes alone on cervicovaginal smears from peri- or postmenopausal women is nonspecific and of no major clinical significance in the absence of other clinical or cytologic findings. (C) 2001 Wiley-Liss, Inc. C1 Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp,James Homer Wright Labs, Boston, MA 02114 USA. RP Tambouret, R (reprint author), Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp,James Homer Wright Labs, 55 Fruit St, Boston, MA 02114 USA. NR 14 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD APR PY 2001 VL 24 IS 4 BP 271 EP 275 DI 10.1002/dc.1058 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 416YL UT WOS:000167808000010 PM 11285625 ER PT J AU Carter, PH Petroni, BD Gensure, RC Schipani, E Potts, JT Gardella, TJ AF Carter, PH Petroni, BD Gensure, RC Schipani, E Potts, JT Gardella, TJ TI Selective and nonselective inverse agonists for constitutively active type-1 parathyroid hormone receptors: Evidence for altered receptor conformations SO ENDOCRINOLOGY LA English DT Article ID JANSENS METAPHYSEAL CHONDRODYSPLASIA; PROTEIN-COUPLED RECEPTORS; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; PTH-RELATED PEPTIDE; N-TERMINAL REGION; BETA(2)-ADRENERGIC RECEPTOR; SIGNAL-TRANSDUCTION; INTERNALIZATION; ANTAGONISTS; ACTIVATION AB The spontaneous signaling activity of some G protein-coupled receptors and the capacity of certain ligands (inverse agonists) to inhibit such constitutive activity are poorly understood phenomena. We investigated these processes for several analogs of PTH-related peptide (PTHrP) and the constitutively active human PTH/PTHrP receptors (hP1Rcs) hP1Rc-H223R and hP1Rc-T410P. The N-terminally truncated antagonist PTHrP(5-36) functioned as a weak partial/neutral agonist with both mutant receptors but was converted to an inverse agonist for both receptors by the combined substitution of Leu(11) and D-Trp(12). The N-terminally intact analog [Bpa(2)]PTHrP(1-36)-a partial agonist with the wild-type hP1Rc-was a selective inverse agonist, in that it depressed basal cAMP signaling by hP1Rc-H223R but enhanced signaling by hP1Rc-T410P. The ability of [Bpa(2)]PTHrP(1-36) to discriminate between the two receptor mutants suggested that H223R and T410P confer constitutive receptor activity by inducing distinct conformational changes. This hypothesis was confirmed by the observations that: 1) the double mutant receptor hP1Rc-H223R/ T410P exhibited basal cAMP levels that were a-fold higher than those of either single mutant; and 2) hP1Rc-H223R and hP1Rc-T410P internalized I-125-PTHrP(5-36) to markedly different extents. The overall results thus reveal that two different types of inverse agonists are possible for PTHrP ligands (nonselective and selective) and that constitutively active PTH-1 receptors can access different conformational states. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM Gardella@helix.MGH.Harvard.edu FU NIDDK NIH HHS [DK-11794] NR 37 TC 27 Z9 28 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2001 VL 142 IS 4 BP 1534 EP 1545 DI 10.1210/en.142.4.1534 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 417QP UT WOS:000167845900021 PM 11250934 ER PT J AU Regan, S Egan, KM Hart, L Gragoudas, ES AF Regan, S Egan, KM Hart, L Gragoudas, ES TI Color Doppler imaging of untreated and irradiated choroidal melanomas SO EUROPEAN JOURNAL OF OPHTHALMOLOGY LA English DT Article DE color Doppler ultrasound; ocular melanoma ID UVEAL MELANOMA; TUMOR VASCULARITY; PROGNOSTIC INDICATOR; CILIARY BODY; ANGIOGENESIS; METASTASIS; SKIN; FLOW AB PURPOSE. We examined untreated and irradiated choroidal melanomas with color Doppler imaging (CDI), a noninvasive method providing quantitative measures of blood flow, to determine if the tumor vessel damage associated with irradiation can be detected using this technology. METHODS. CDI was performed on 122 untreated and 76 previously irradiated tumors using a Q2000 color Doppler ultrasound unit. Spectral analysis was performed on all detectable vascular regions within the tumor to obtain estimates of the peak systolic and end diastolic flow velocities and resistive index ((syst-diast)/syst). RESULTS. Vessels were detected in 93% of the untreated tumors and in 63% of the treated tumors (p < 0.001, X-2), and the median number of vascular regions found was higher among untreated tumors (3 vs I, p = 0.001, Wilcoxon Rank Sum). The effect of treatment status on the detection of tumor vessels was significant (p = 0.039), controlling for age, sex, largest tumor pretreatment diameter, and tumor height at CDI in a logistic regression model. Mean resistive index was lower in the untreated tumors (0.53 vs 0.58, p = 0.0050), controlling for tumor height and other covariates in an analysis of variance. CONCLUSIONS. On examination with CDI, irradiated tumors had fewer detectable vascular regions and greater resistance to flow than untreated tumors, a pattern consistent with known radiation effects. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP Gragoudas, ES (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 241 Charles St, Boston, MA 02114 USA. NR 16 TC 5 Z9 5 U1 0 U2 1 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1120-6721 J9 EUR J OPHTHALMOL JI Eur. J. Ophthalmol. PD APR-JUN PY 2001 VL 11 IS 2 BP 150 EP 155 PG 6 WC Ophthalmology SC Ophthalmology GA 450AL UT WOS:000169719300008 PM 11456016 ER PT J AU Goke, MN Cook, JR Kunert, KS Fini, ME Gipson, IK Podolsky, DK AF Goke, MN Cook, JR Kunert, KS Fini, ME Gipson, IK Podolsky, DK TI Trefoil peptides promote restitution of wounded corneal epithelial cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE ocular surface; corneal wound healing; cell migration ID EPIDERMAL GROWTH-FACTOR; CONJUNCTIVAL GOBLET CELLS; HUMAN RESPIRATORY-TRACT; RABBIT CORNEA; FACTOR-BETA; IN-VITRO; MIGRATION; EXPRESSION; FAMILY; PROLIFERATION AB The ocular surface shares many characteristics with mucosal surfaces. In both, healing is regulated by peptide growth factors, cytokines, and extracellular matrix proteins. However, these factors are not sufficient to ensure most rapid healing. Trefoil peptides are abundantly expressed epithelial cell products which exert protective effects and are key regulators of gastrointestinal epithelial restitution, the critical early phase of cell migration after mucosal injury, To assess the role of trefoil peptides in corneal epithelial wound healing, the effects of intestinal trefoil factor (ITF/ TFF3) and spasmolytic polypeptide (SP/TFF2) on migration and proliferation of corneal epithelial cells were analyzed. Both ITF and SP enhanced restitution of primary rabbit corneal epithelial cells in vitro. While the restitution-enhancing effects of TGF-alpha and TGF-beta were both inhibited by neutralizing anti-TGF-beta -antibodies, trefoil peptide stimulation of restitution was not. Neither trefoil peptide significantly affected proliferation of primary corneal epithelial cells. ITF but not SP or pS2 mRNA was present in rabbit corneal and conjunctival tissues. In summary, the data indicate an unanticipated role of trefoil peptides in healing of ocular surface and demand rating their functional actions beyond the gastrointestinal tract. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Tufts Univ, New England Eye Ctr, Sch Med, Vis Res Lab, Boston, MA 02111 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-719, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK41557, DK 46768] NR 47 TC 29 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 1 PY 2001 VL 264 IS 2 BP 337 EP 344 DI 10.1006/excr.2000.5116 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 417QF UT WOS:000167845100015 PM 11262190 ER PT J AU Cruz, JC Alsina, M Craig, F Yoneda, T Anderson, JL Dallas, M Roodman, GD AF Cruz, JC Alsina, M Craig, F Yoneda, T Anderson, JL Dallas, M Roodman, GD TI Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID HUMAN MARROW CULTURES; MULTIPLE-MYELOMA; INHIBITOR; BISPHOSPHONATES; PRECURSORS; RESORPTION; APOPTOSIS; PHENOTYPE; LESIONS; POTENT AB Objective. The benefits of bisphosphonate therapy for multiple myeloma bone disease have been clearly documented. However, the effects of bisphosphonates on the osteoclast stimulatory activity (OSA) that is present in the marrow of patients with multiple myeloma, even before the bone disease is detectable, are unknown. Therefore, we examined the effects of ibandronate (IB) treatment prior to the development of bone disease in a murine model of human myeloma. Materials and Methods. Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted with ARH-77 cells on day 0. These ARH-77 mice were treated daily with subcutaneous injections of IB started before or at different times after tumor injection as follows: group 1 was started on day -7; group 2 on day 0; group 3 on day +7; group 3 on day +14 after IB administration; and group 5 (control) received no IB. h lice were sacrificed after they developed paraplegia. Results. The onset of paraplegia was delayed in group 1 vs all other groups (mean day 27 vs day 32; p = 0.0098). The number of lytic lesions and the bone surface area of resorption (mm(2)) were significantly decreased in groups 1, 2, and 3, which were treated early with IB, when compared with groups 4 and 5 (p = 0.003 and 0.002, respectively). OSA, as measured by the capacity of bone marrow plasma from ARH-77 mice to induce osteoclast (OCL) formation in human bone marrow cultures, was decreased proportionally to the length of IB treatment. Group 1 had the lowest OSA compared with the other groups (p = 0.003). However, all mice eventually developed paraplegia, and at time of sacrifice, turner burden was not grossly different among the groups. Interestingly, macroscopic abdominal tumors were more frequent in mice treated with IB. Conclusion. These data demonstrate that early treatment of ARH-77 mice with IB prior to development of myeloma bone disease decreases OSA and possibly retards the development of lytic lesions, but not eventual tumor burden. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Audie L Murphy Mem Vet Hosp, Res Serv 151, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Gen Clin Res Ctr, San Antonio, TX 78284 USA. Texas Tech Univ, Dept Med, Lubbock, TX 79409 USA. Texas Tech Univ, Hlth Sci Ctr, Div Hematol, Lubbock, TX 79409 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Pathol, Lubbock, TX 79409 USA. Texas Tech Univ, Hlth Sci Ctr, Div Endocrinol, Lubbock, TX 79409 USA. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Hosp, Res Serv 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NCI NIH HHS [CA40035, CA69136] NR 23 TC 40 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 2001 VL 29 IS 4 BP 441 EP 447 DI 10.1016/S0301-472X(01)00618-X PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 419MP UT WOS:000167953100006 PM 11301184 ER PT J AU Quinn, J Davis, F Woodward, WR Eckenstein, F AF Quinn, J Davis, F Woodward, WR Eckenstein, F TI beta-amyloid plaques induce neuritic dystrophy of nitric oxide-producing neurons in a transgenic mouse model of Alzheimer's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE stress; oxidative; free radicals; disease models; animal ID NADPH-DIAPHORASE; OXIDATIVE STRESS; PRECURSOR PROTEIN; IN-VIVO; HIPPOCAMPAL-NEURONS; ALPHA-TOCOPHEROL; MEMORY DEFICITS; NEUROTOXICITY; MICE; SYNTHASE AB A causative role for nitric oxide has been postulated in a number of neurodegenerative diseases. Using histochemical and immunohistochemical methods, we examined the effect of beta -amyloid plaques on nitric oxide-producing cells in transgenic mice which overexpress a mutant human amyloid precursor protein (APP). In 14-month-old animals, nitric oxide synthase (NOS)positive dystrophic neurites were observed frequently in the cerebral cortex and hippocampus of all of 16 plaque-bearing transgenic animals and in none of 16 wild-type animals. Double labeling of NOS and beta -amyloid revealed that 90% of beta -amyloid plaques were associated with NOS-containing dystrophic neurites. In 7-month-old animals, beta -amyloid plaques were very rare, but those present were frequently associated with NOS-positive neuritic dystrophy, We conclude that beta -amyloid plaques induce neuritic dystrophy in cortical neurons containing NOS in this model of AD, and hypothesize that this finding may be relevant to the mechanism of beta -amyloid neurotoxicity in human AD. (C) 2001 Academic Press. C1 Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. OHSU, Dept Cellular & Dev Biol, Portland, OR 97201 USA. OHSU, Dept Neurol, Portland, OR 97201 USA. RP Quinn, J (reprint author), Portland Vet Affairs Med Ctr, P3 R&D,SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NCCIH NIH HHS [AT00066-01]; NIA NIH HHS [AG08017, AG07424] NR 58 TC 15 Z9 16 U1 0 U2 1 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 APR PY 2001 VL 168 IS 2 BP 203 EP 212 DI 10.1006/exnr.2000.7598 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 418RA UT WOS:000167904100001 PM 11259108 ER PT J AU Yamada, M Natsume, A Mata, M Oligino, T Goss, J Glorioso, J Fink, DJ AF Yamada, M Natsume, A Mata, M Oligino, T Goss, J Glorioso, J Fink, DJ TI Herpes simplex virus vector-mediated expression of Bcl-2 protects spinal motor neurons from degeneration following root avulsion SO EXPERIMENTAL NEUROLOGY LA English DT Article DE gene therapy; herpes simplex; apoptosis; motor neuron; trauma ID INDUCED CELL-DEATH; CILIARY NEUROTROPHIC FACTOR; NERVE GROWTH-FACTOR; CHOLINE-ACETYLTRANSFERASE; NEONATAL MOTONEURONS; HYPOGLOSSAL NUCLEUS; TRANSGENIC MICE; GENE-TRANSFER; MOUSE MODEL; IN-VIVO AB Proximal axotomy in adult animals results in delayed death of motor neurons. Features characteristic of both necrosis and apoptosis have been described in motor neurons of the spinal cord following proximal avulsion of the ventral roots. We have previously demonstrated that a genomic herpes simplex virus (HSV)based vector expressing the anti-apoptotic peptide Bcl-2 protects dopaminergic neurons of the substantia nigra from neurotoxin-induced apoptotic cell death and preserves the neurotransmitter phenotype of those cells. In this study we examined whether the same vector could protect adult rat lumbar motor neurons from cell death following proximal ventral root avulsion. Injection of the Bcl-2-expressing vector 1 week prior to root avulsion increased the survival of lesioned motor neurons, determined by retrograde Fluorogold labeling, by 50%. The Bcl-8-expressing vector did not preserve choline acetyltransferase neurotransmitter phenotype of the lesioned cells. These results shed light on the mechanism of cell death following axonal injury, and have implications for developing an effective treatment for the clinical problem of proximal root avulsion, (C) 2001 Academic Press. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. GRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Fink, DJ (reprint author), S-520 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. RI Natsume, Atsushi/I-7364-2014 OI Natsume, Atsushi/0000-0002-9113-0470 NR 35 TC 36 Z9 43 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 APR PY 2001 VL 168 IS 2 BP 225 EP 230 DI 10.1006/exnr.2000.7597 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 418RA UT WOS:000167904100003 PM 11259110 ER PT J AU Noll, ENE Lin, J Nakatsuji, Y Miller, RH Black, PM AF Noll, ENE Lin, J Nakatsuji, Y Miller, RH Black, PM TI GM3 as a novel growth regulator for human gliomas SO EXPERIMENTAL NEUROLOGY LA English DT Article DE glial tumors; cell death; gangliosides; cell proliferation; astrocytes; oligodendrocytes ID NEURO-BLASTOMA; TYROSINE PHOSPHORYLATION; GANGLIOSIDE COMPOSITION; BRAIN-DEVELOPMENT; FACTOR RECEPTOR; CELLS; RAT; DIFFERENTIATION; OUTGROWTH; THERAPY AB The simple ganglioside GM3 inhibits proliferation and induces apoptosis in proliferating immature rodent CNS cells. To determine whether GM3 influenced the expansion of human neural tumors the effects of GM3 treatment on primary human brain tumors were assayed. Here we demonstrate that GM3 treatment dramatically reduces cell numbers in primary cultures of high-grade human glioblastoma multiforme (GBM) tumors and the rat 9L cell gliosarcoma cell line. By contrast, GM3 treatment had little effect on cell number in cultures of normal human brain. A single injection of GM3 3 days after intracranial implantation of 9L tumor cells in a murine xenograft model system resulted in a significant increase in the symptom-free survival period of host animals. The effects of GM3 were not restricted to GBMs and 9L cells. Cultures of high-grade ependymomas, mixed gliomas, astrocytomas, oligodendrogliomas, and gangliogliomas were all susceptible to GM3 treatment. These results suggest that GM3 may have considerable value as a selectively toxic chemotherapeutic agent for human high-grade gliomas, (C) 2001 Academic Press. C1 Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Childrens Hosp, Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Neurosurg, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Miller, RH (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. FU NINDS NIH HHS [NS 36674] NR 54 TC 26 Z9 30 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 APR PY 2001 VL 168 IS 2 BP 300 EP 309 DI 10.1006/exnr.2000.7603 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 418RA UT WOS:000167904100011 PM 11259118 ER PT J AU Andreassen, OA Ferrante, RJ Klivenyi, P Klein, AM Dedeoglu, A Albers, DS Kowall, NW Beal, MF AF Andreassen, OA Ferrante, RJ Klivenyi, P Klein, AM Dedeoglu, A Albers, DS Kowall, NW Beal, MF TI Transgenic ALS mice show increased vulnerability to the mitochondrial toxins MPTP and 3-nitropropionic acid SO EXPERIMENTAL NEUROLOGY LA English DT Article DE mitochondria; Parkinson's disease; amyotrophic lateral sclerosis; oxidative damage; 3-nitropropionic acid; MPTP ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU,ZN SUPEROXIDE-DISMUTASE; PARKINSONS-DISEASE; HYDROGEN-PEROXIDE; ANIMAL-MODEL; IN-VIVO; K-M; MUTATION; DEGENERATION; NEURONS AB The pathogenesis of neurodegenerative diseases may involve a genetic predisposition acting in concert with environmental toxins. To test this hypothesis we examined whether transgenic mice with the G93A mutation in Cu,Zn superoxide dismutase show increased vulnerability to either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 3-nitropropionic acid (3-NP), Compared to littermate controls G93A transgenic mice showed a greater loss of striatal dopamine, DOPAC, and HVA at 50, 70, and 120 days of age following administration of MPTP; however, cell loss in the substantia nigra was not greater. The G93A transgenic mice showed significantly increased vulnerability to striatal lesions produced by 3-NP compared with littermate controls at 120 days of age. The finding that G93A mice show increased vulnerability to mitochondrial toxins further implicates mitochondrial dysfunction in the pathogenesis of neuronal death in these mice. The findings support the hypothesis that a genetic defect can increase susceptibility to environmental toxins and that this may play a role in the pathogenesis of neurodegenerative diseases. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Neurol, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Dept Vet Affairs, Bedford, MA USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. RP Andreassen, OA (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA NIH HHS [P01 AG12292]; NINDS NIH HHS [NS37102, NS31579, NS35255] NR 40 TC 16 Z9 16 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 APR PY 2001 VL 168 IS 2 BP 356 EP 363 DI 10.1006/exnr.2001.7627 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 418RA UT WOS:000167904100016 PM 11259123 ER PT J AU Andreassen, OA Dedeoglu, A Friedlich, A Ferrante, KL Hughes, D Szabo, C Beal, MF AF Andreassen, OA Dedeoglu, A Friedlich, A Ferrante, KL Hughes, D Szabo, C Beal, MF TI Effects of an inhibitor of poly(ADP-ribose) polymerase, desmethylselegiline, trientine, and lipoic acid in transgenic ALS mice SO EXPERIMENTAL NEUROLOGY LA English DT Article DE apoptosis; oxidative damage; free radicals; copper; amyotrophic lateral sclerosis; trienterine; lipoic acid; poly(ADP-ribose) polymerase ID AMYOTROPHIC-LATERAL-SCLEROSIS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; SUPEROXIDE-DISMUTASE; CEREBRAL-ISCHEMIA; IN-VITRO; PEROXYNITRITE; APOPTOSIS; SOD1; DEGENERATION; DISEASE AB The development of transgenic mouse models of amyotrophic lateral sclerosis (ALS) allows the testing of neuroprotective agents. We evaluated the effects of five agents in transgenic mice with the G93A Cu,Zn superoxide dismutase mutation. A novel inhibitor of poly(ADP-ribose) polymerase showed no effects on survival. Desmethylselegiline and CGP3466 are agents that exert antiapoptotic effects in vitro by preventing nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase, They had no significant effects on survival in the G93A mice. Trientine, a copper chelator, produced a modest significant increase in survival, Similarly administration of lipoic acid in the diet produced a significant improvement in survival. These results therefore provide evidence for potential therapeutic effects of copper chelators and lipoic acid in the treatment of ALS. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Inotek Corp, Beverly, MA 01915 USA. RP Andreassen, OA (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. FU NIA NIH HHS [P01-AG12292] NR 34 TC 53 Z9 56 U1 0 U2 2 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 APR PY 2001 VL 168 IS 2 BP 419 EP 424 DI 10.1006/exnr.2001.7633 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 418RA UT WOS:000167904100023 PM 11259130 ER PT J AU Andreadis, ST Hamoen, KE Yarmush, ML Morgan, JR AF Andreadis, ST Hamoen, KE Yarmush, ML Morgan, JR TI Keratinocyte growth factor induces hyperproliferation and delays differentiation in a skin equivalent model system SO FASEB JOURNAL LA English DT Article DE KGF; fibroblast growth factor; cell proliferation; rete ridges ID HUMAN EPIDERMAL-CELLS; TERMINAL DIFFERENTIATION; FACTOR EXPRESSION; ELECTRICAL CAPACITANCE; DEVELOPMENT SUGGESTS; LAMELLAR ICHTHYOSIS; BARRIER FUNCTION; ATHYMIC MICE; GENE; RECEPTOR AB Keratinocyte growth factor (KGF) is a paracrine mediator of epithelial cell growth. To examine the direct effects of KGF on the morphogenesis of the epidermis, we generated skin equivalents in vitro by seeding human keratinocytes on the papillary surface of acellular dermis and raising them up to the air-liquid interface. KGF was either added exogenously or expressed by keratinocytes via a recombinant retrovirus encoding KGF. KGF induced dramatic changes to the 3-dimensional organization of the epidermis including pronounced hyperthickening, crowding, and elongation of the basal cells, flattening of the rete ridges, and a ripple-like pattern in the junction of stratum corneum and granular layers. Quantitative immunostaining for the proliferation antigen, Ki67, revealed that in addition to increasing basal proliferation, KGF extended the proliferative compartment by inducing suprabasal cell proliferation. KGF also induced expression of the integrin alpha5 beta1 and delayed expression of keratin 10 and transglutaminase, However, barrier formation of the epidermis was not disrupted. These results demonstrate for the first time that a single growth factor can alter the 3-dimensional organization and proliferative function of an in vitro epidermis, In addition to new strategies for tissue engineering, such a well-defined system will be useful for analyzing growth factor effects on the complex links between cell proliferation, cell movement and differentiation within a stratified tissue. C1 Shriners Burn Hosp, Boston, MA 02114 USA. 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. RP Morgan, JR (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM jmorgan@sbi.org OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [HD-28528] NR 44 TC 96 Z9 105 U1 0 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2001 VL 15 IS 6 BP 898 EP 906 DI 10.1096/fj.00-0324com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 419QC UT WOS:000167959300003 PM 11292649 ER PT J AU Bo-Abbas, YY Martin, KA Liberman, RF Cramer, DW Barbieri, RL AF Bo-Abbas, YY Martin, KA Liberman, RF Cramer, DW Barbieri, RL TI Serum and follicular fluid hormone levels during in vitro fertilization after short- or long-course treatment with a gonadotropin-releasing hormone agonist SO FERTILITY AND STERILITY LA English DT Article DE androgens; IVF; leuprolide acetate ID GAMETE INTRAFALLOPIAN TRANSFER; HUMAN MENOPAUSAL GONADOTROPIN; INVITRO FERTILIZATION; OVARIAN STIMULATION; LUTEINIZING-HORMONE; CLOMIPHENE CITRATE; HUMAN OOCYTES; LUTEAL-PHASE; GNRH-A; CYCLES AB Objective: To examine the impact of flare (short) vs. down-regulation (long) GnRH agonist (GnRH-a) on serum and follicular fluid (FF) LH and androgen concentrations in women undergoing IVF treatment cycles. Design: Prospective observational study. Setting: IVF clinic. Patient(s): One hundred sixteen ovulatory subjects undergoing IVF. Intervention(s): Fifty-eight ovulatory patients undergoing a down-regulation regimen matched with 58 undergoing the flare regimen as part of an IVF cycle. Main Outcome Measure(s): Serum concentrations of LH, FSH, Progesterone (P4), Androstenedione (A), T, and a on the day of hCG administration were compared between the two groups. In addition, the FF P4, 170HP4. A, T. and E-2 levels were compared in the two groups. Result(s): Serum LH was significantly higher with the flare regimen (15.2 +/- 1.14 IU/L, P<.05) when compared with results with the down-regulation protocol (9.5 : 0.77 IU/L). In addition, FF A was significantly higher in the flare protocol (57.3 +/- 13.3 ng/mL, P<.05) compared with in the dawn-regulation protocol (27 2.44 ng/mL). Serum and FF P4, 170H P4, T, and E, were not statistically significantly different between the two groups. Conclusion(s): Serum LH and FF A are significantly higher in the flare regimen in comparison with the down-regulation regimen. Circulating LH appears to play a role in determining FF a concentration. (C) 2001 by American Society for Reproductive Medicine. C1 Brigham & Womens Hosp, Infertil Obstet & Gynecol Epidemiol Unit, Dept Obstet & Gynecol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Cramer, DW (reprint author), Brigham & Womens Hosp, Infertil Obstet & Gynecol Epidemiol Unit, Dept Obstet & Gynecol, 221 Longwood Ave, Boston, MA 02115 USA. FU NCRR NIH HHS [RR1066]; NICHD NIH HHS [U54HD29164, R01HD32153] NR 40 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD APR PY 2001 VL 75 IS 4 BP 694 EP 699 DI 10.1016/S0015-0282(01)01676-4 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 419QL UT WOS:000167960100010 PM 11287021 ER PT J AU Ginsburg, ES Yanushpolsky, EH Jackson, KV AF Ginsburg, ES Yanushpolsky, EH Jackson, KV TI In vitro fertilization for cancer patients and survivors SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY SEP 25-29, 1999 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Reprod Med DE cancer; in vitro fertilization; embryo transfer; cryopreservation; embryo; bone marrow transplant; breast cancer ID INFERTILE WOMEN; FERTILITY; CAPACITY; COHORT; RISK AB Objective: To determine in vitro fertilization (IVF) outcome in cancer patients. Design: Retrospective record review. Setting: Academic, hospital-based assisted reproductive technology (ART) program. Patient(s): Sixty-nine women undergoing 113 IVF/gamete intrafallopian transfer (GIFT) cycles after cancer treatment in one partner, and 13 women undergoing 13 IVF cycles for embryo cryopreservation before chemotherapy/radiation. Intervention(s): IVF, intracytoplasmic sperm injection (ICSI), assisted hatching, and gamete intrafallopian transfer as indicated. Main Outcome Measure(s): Delivery rate, spontaneous abortion rate, number of embryos cryopreserved, cancer diagnosis, systemic or local cancer treatment, female age, amount of gonadotropin used, treatment duration, peak estradiol level, and number of oocytes and embryos. Result(s): The women undergoing IVF after chemotherapy had poorer responses to gonadotropins than did the women with locally treated cancers even though they were younger (33.5 +/- 1.3 vs. 36.5 +/- 0.5 years; P<.05). The delivery rates after the women had undergone chemotherapy tended to be lower among the systemic treatment group than it was for the local cancer treatment group: (13.3% [2 of 15] vs. 40% [14 of 56, P=NS]). The women who had cryopreserved all embryos before chemotherapy produced more oocytes (18.7 3.2 vs. 14.5 +/- 1.2) and embryos (11.3 +/- 1.9 vs. 7.5 +/- 0.7) than did the women who had had a history of local cancer treatment. Male factor infertility as a result of cancer treatment is well treated with IVF or intracytoplasmic sperm injection, where indicated (32% delivery rate/cycle), with no difference between the frozen sperm banked before cancer treatment and fresh sperm produced after treatment. Conclusion(s): Chemotherapy diminishes the response to ovulation induction in assisted reproductive technologies. IVF with cryopreservation of embryos allows embryo banking before chemotherapy for women who have been newly diagnosed with cancer. Factors related to the partner affect the success of IVF for male factor infertility as a result of cancer treatment. (C) 2001 by American Society for Reproductive Medicine. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Reprod Endocrinol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ginsburg, ES (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Reprod Endocrinol, 75 Francis St,ASB 1,3rd Floor, Boston, MA 02115 USA. NR 7 TC 55 Z9 62 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD APR PY 2001 VL 75 IS 4 BP 705 EP 710 DI 10.1016/S0015-0282(00)01802-1 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 419QL UT WOS:000167960100012 PM 11287023 ER PT J AU Akiba, Y Furukawa, O Guth, PH Engel, E Ishii, H Kaunitz, JD AF Akiba, Y Furukawa, O Guth, PH Engel, E Ishii, H Kaunitz, JD TI Intracellular bicarbonate protects rat duodenal mucosa from acid-induced injury SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Keio Univ, Sch Med, Tokyo, Japan. W Los Angeles VAMC, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 793 BP A148 EP A149 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700731 ER PT J AU Ang, P Schrag, D Schneider, K Shannon, K Johnson, J Hiller, E Emmons, K Garber, J Syngal, S AF Ang, P Schrag, D Schneider, K Shannon, K Johnson, J Hiller, E Emmons, K Garber, J Syngal, S TI Colorectal cancer knowledge and screening rates are lower than for breast cancer even in individuals at high risk of cancer SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Natl Canc Ctr, Singapore, Singapore. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2001 VL 120 IS 5 SU 1 MA 3985 BP A741 EP A741 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703686 ER PT J AU Arnold, CN Goel, A Chang, DK Wasserman, L Compton, C Niedzwiecki, D Mayer, RJ Bertagnolli, MM Boland, CR AF Arnold, CN Goel, A Chang, DK Wasserman, L Compton, C Niedzwiecki, D Mayer, RJ Bertagnolli, MM Boland, CR TI Microsatellite high (MSI-H) tumors are not associated with LOH at the APC locus compared to microsatellite-low/stable (MSI-L/MSS) tumors SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. McGill Univ, Dept Pathol, Montreal, PQ, Canada. Duke Univ, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. VAMC, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1531 BP A296 EP A296 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701467 ER PT J AU Arnold, CN Goel, A Carethers, JM Wasserman, L Compton, C Niedzwiecki, D Mayer, RJ Bertagnolli, MM Boland, CR AF Arnold, CN Goel, A Carethers, JM Wasserman, L Compton, C Niedzwiecki, D Mayer, RJ Bertagnolli, MM Boland, CR TI A panel of mono- and dinucleotide microsatellite markers is required for reliable determination of the MSI status in colorectal cancer SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. VAMC, La Jolla, CA USA. McGill Univ, Montreal, PQ, Canada. Duke Univ, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2001 VL 120 IS 5 SU 1 MA 3040 BP A599 EP A599 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702970 ER PT J AU Balcom, JH Keck, T Antoniu, B Warshaw, AL Lauwers, GY Castillo, CF AF Balcom, JH Keck, T Antoniu, B Warshaw, AL Lauwers, GY Castillo, CF TI Perioperative matrix metalloproteinase inhibition therapy does not impair wound or anastomotic healing SO GASTROENTEROLOGY 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 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 APR PY 2001 VL 120 IS 5 SU 1 MA 2049 BP A400 EP A400 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701984 ER PT J AU Balcom, JH Keck, T Antoniu, B Warshaw, AL Graeme-Cook, F Fernandez-Del Castillo, C AF Balcom, JH Keck, T Antoniu, B Warshaw, AL Graeme-Cook, F Fernandez-Del Castillo, C TI Prevention of clinically significant pancreatic fistulae with a new synthetic, absorbable sealant after distal pancreatectomy in the normal dog SO GASTROENTEROLOGY 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 1 U2 1 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 APR PY 2001 VL 120 IS 5 SU 1 MA 1800 BP A350 EP A350 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701735 ER PT J AU Bandipalliam, P Lunetta, K Syngal, S AF Bandipalliam, P Lunetta, K Syngal, S TI Meta-analysis of genotype-phenotype correlations in Familial Adenomatous Polyposis SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3974 BP A739 EP A739 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703675 ER PT J AU Bashir, MEH Shi, HN Andersen, P Melendro, EI Nagler-Anderson, C AF Bashir, MEH Shi, HN Andersen, P Melendro, EI Nagler-Anderson, C TI Enteric helminth infection does not induce an allergic response to a food antigen SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1650 BP A320 EP A320 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701586 ER PT J AU Brand, SA Sakaguchi, T Gu, XB Colgan, SP Reinecker, HC AF Brand, SA Sakaguchi, T Gu, XB Colgan, SP Reinecker, HC TI CX3CR1 mediated signals regulate cell-survival and immune-modulatory mediators in Intestinal Epithelial Cells (IEG) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 310 BP A59 EP A59 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700291 ER PT J AU Cario, E Mizoguchi, E Mizoguchi, A Bhan, AK Podolsky, DK AF Cario, E Mizoguchi, E Mizoguchi, A Bhan, AK Podolsky, DK TI TLR expression is selectively altered in murine models of inflammatory bowel disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, CSIBD,Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, CSIBD,Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1012 BP A192 EP A192 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700950 ER PT J AU Chitkara, DK Schoffner, J Buie, T Flores, A AF Chitkara, DK Schoffner, J Buie, T Flores, A TI Abnormalities in gastrointestinal motility as a presentation of diseases of oxidative phosphorylation in children. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Tufts Univ, Sch Med, Floating Hosp Children, Boston, MA 02111 USA. Childrens Healthcare Atlanta, Atlanta, GA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1190 BP A227 EP A227 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701126 ER PT J AU Dai, CY Gibson, SL Gee, MS Lee, WM Lee, HW Depinho, RA Enders, GH AF Dai, CY Gibson, SL Gee, MS Lee, WM Lee, HW Depinho, RA Enders, GH TI Suppression of mouse colon tumor angiogenesis by the INK4a/ARF locus. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Sungkyunkwan Univ, Seoul, South Korea. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1530 BP A296 EP A296 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701466 ER PT J AU De Jong, YP Coyle, AJ Rietdijk, ST Mizoguchi, E Bhan, AK Gutierrez-Ramos, JC Terhorst, C AF De Jong, YP Coyle, AJ Rietdijk, ST Mizoguchi, E Bhan, AK Gutierrez-Ramos, JC Terhorst, C TI Blocking ICOS in combination with CD28 impairs the proper activation of aggressor Th1 cells but is not necessary for suppression by regulatory T cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Millenium Pharmaceut, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 244 BP A47 EP A47 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700230 ER PT J AU Doble, MA Tola, VB Chamberlain, SL Van Hoek, A Soybel, DI AF Doble, MA Tola, VB Chamberlain, SL Van Hoek, A Soybel, DI TI Luminal regulation of Na+/H+ exchanger (NHE) gene expression in rat ileal mucosa SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Boston VA Healthcare Syst, W Roxbury, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2001 VL 120 IS 5 SU 1 MA 1804 BP A350 EP A351 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701739 ER PT J AU Dulai, GS Chen, J Oh, D Jensen, DM Shekelle, P Ganz, P Gornbein, J AF Dulai, GS Chen, J Oh, D Jensen, DM Shekelle, P Ganz, P Gornbein, J TI Cancer risk, EGD biopsy workload & reporting in a VA Barrett's cohort SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. GLAVAHCS, CURE, Los Angeles, CA USA. Univ Calif Los Angeles, GLAVAHCS, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2129 BP A416 EP A417 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702064 ER PT J AU El-Serag, HB Everhart, JE Richardson, PA AF El-Serag, HB Everhart, JE Richardson, PA TI Risk factors for hepatocellular carcinoma: A case control study among US veterans. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1191 BP A227 EP A227 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701127 ER PT J AU El-Serag, HB Bailey, N Gilger, M Rabeneck, L AF El-Serag, HB Bailey, N Gilger, M Rabeneck, L TI Absence of Barrett's esophagus in neurologically normal children with gastroesophageal reflux disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Texas Childrens Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2109 BP A412 EP A412 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702044 ER PT J AU El-Serag, HB Kunik, M Richardson, PA Rabeneck, L AF El-Serag, HB Kunik, M Richardson, PA Rabeneck, L TI Psychiatric and drug use disorders among veterans infected with hepatitis C virus. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2092 BP A409 EP A409 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702027 ER PT J AU El-Zimaity, HMT Katsuyama, T Ota, H Watanabe, H Hattori, T Graham, DY AF El-Zimaity, HMT Katsuyama, T Ota, H Watanabe, H Hattori, T Graham, DY TI Gastric histology in patients with carcinoma at the gastro-esophageal junction SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Shinshu Univ Hosp, Matsumoto, Nagano, Japan. Shiga Univ Med Sci, Shiga, Japan. Niigata Univ, Niigata, Japan. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1292 BP A249 EP A249 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701228 ER PT J AU El-Zimaity, HMT Kim, JG Graham, DY AF El-Zimaity, HMT Kim, JG Graham, DY TI Clarification of clinical relevance of gastric intestinal metaplasia SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Korea Univ, Coll Med, Seoul 136701, South Korea. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3083 BP A607 EP A607 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703013 ER PT J AU Esnaola, NF Lauwers, GY Mirza, NQ Nagorney, DM Doherty, DA Ikai, I Belghiti, J Yamaoka, Y Curley, SA Ellis, LM Vauthey, JN AF Esnaola, NF Lauwers, GY Mirza, NQ Nagorney, DM Doherty, DA Ikai, I Belghiti, J Yamaoka, Y Curley, SA Ellis, LM Vauthey, JN TI Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplanation. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Kyoto Univ, Grad Sch Med, Kyoto, Japan. Hosp Beaujon, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 483 BP A90 EP A90 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700443 ER PT J AU Farrell, JJ Taupin, D Koh, T Podolsky, DK Wang, TC AF Farrell, JJ Taupin, D Koh, T Podolsky, DK Wang, TC TI Targetted gene deletion of murine SP/TTF2 results in decreased gastric proliferation, increased basal acid secretion and increased susceptibility to NSAID injury SO GASTROENTEROLOGY 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 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 APR PY 2001 VL 120 IS 5 SU 1 MA 744 BP A139 EP A139 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700682 ER PT J AU Furukawa, O Hirokawa, M Guth, PH Engel, E Itz, JDK AF Furukawa, O Hirokawa, M Guth, PH Engel, E Itz, JDK TI Role of protein kinases on acid-induced duodenal bicarbonate secretion in rats SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles VAMC, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 830 BP A156 EP A156 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700768 ER PT J AU Germano, PM Le, S Fan, R Pisegna, JR AF Germano, PM Le, S Fan, R Pisegna, JR TI The PACAP Type I receptor (PAC1) is expressed and is coupled to signaling cascades in human colonic tumors SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Med, Digest Dis Res Ctr, CURE, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Digest Dis Res Ctr, CURE, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA GLAHS, Div GI, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2516 BP A494 EP A494 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702449 ER PT J AU Goel, A Arnold, CN Ricciardiello, L Chang, DK Wasserman, L Compton, C Niedzwiecki, D Mayer, RJ Bertagnolli, MM Boland, R AF Goel, A Arnold, CN Ricciardiello, L Chang, DK Wasserman, L Compton, C Niedzwiecki, D Mayer, RJ Bertagnolli, MM Boland, R TI Somatic frameshift mutations in MBD4 (MED1) are not exclusively associated with microsatellite high (MSI-H) colorectal tumors SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif San Diego, Ctr Canc, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. McGill Univ, Dept Pathol, Montreal, PQ, Canada. Duke Univ, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. VAMC, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1516 BP A293 EP A293 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701452 ER PT J AU Goel, A Arnold, CN Chang, DK Ricciardiello, L Chauhan, DP Carethers, JM Wasserman, L Compton, C Niedzwiecki, D Mayer, RJ Bertagnolli, MM Boland, CR AF Goel, A Arnold, CN Chang, DK Ricciardiello, L Chauhan, DP Carethers, JM Wasserman, L Compton, C Niedzwiecki, D Mayer, RJ Bertagnolli, MM Boland, CR TI Chromosomal vs microsatellite instability in colorectal cancers: Evidence for previously unrecognized pathways SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. VAMC, La Jolla, CA USA. McGill Univ, Dept Pathol, Montreal, PQ, Canada. Duke Univ, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR PY 2001 VL 120 IS 5 SU 1 MA 867 BP A163 EP A163 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700805 ER PT J AU Graham, DY Osato, MS El-Zimaity, HMT AF Graham, DY Osato, MS El-Zimaity, HMT TI Azithromycin triple therapy for Helicobacter pylori infection SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2955 BP A581 EP A582 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702885 ER PT J AU Gralnek, IM Hays, RD Kilbourne, A Mayer, EA AF Gralnek, IM Hays, RD Kilbourne, A Mayer, EA TI Racial differences in the impact of irritable bowel syndrome (IBS) on health-related quality of life (HRQOL) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RI Hays, Ronald/D-5629-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 4073 BP A759 EP A759 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703774 ER PT J AU Hisamatsu, T Poneros, JM Tearney, GJ Bouma, BE Nishioka, NS Podolsky, DK AF Hisamatsu, T Poneros, JM Tearney, GJ Bouma, BE Nishioka, NS Podolsky, DK TI In vivo monitoring of intestinal wound healing using optical coherence tomography SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 800 BP A150 EP A150 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700738 ER PT J AU Hokama, A Tanaka, Y Mizaguchi, E Snapper, SB Bhan, AK Mizoguchi, A AF Hokama, A Tanaka, Y Mizaguchi, E Snapper, SB Bhan, AK Mizoguchi, A TI Colonic epithelial cell-derived galectin-4 as a potential pathogenic mediator in the chronic colitis of TCR alpha knockout mice SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 655 BP A122 EP A122 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700599 ER PT J AU Huang, L Koziel, MJ Fowler, N Schmidt, E AF Huang, L Koziel, MJ Fowler, N Schmidt, E TI Hepatocytes expressing HCV structural proteins enhance apoptosis of activated T cells SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 33 BP A7 EP A7 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700034 ER PT J AU Huerta, S Sebastian, J Heber, D Licinio, J Wong, ML Hannestad, J Livingston, EH AF Huerta, S Sebastian, J Heber, D Licinio, J Wong, ML Hannestad, J Livingston, EH TI Downregulation of homeobox genes HOX1, HOX2 and HOX7 in metastatic colon cancer SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1534 BP A297 EP A297 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701470 ER PT J AU Huerta, S Heber, D Licinio, J Wong, ML Hannestad, J Livingston, EH AF Huerta, S Heber, D Licinio, J Wong, ML Hannestad, J Livingston, EH TI Large scale expression array analysis of a colon cancer progression model reveals altered regulation of 1251 genes including the downregulation of transglutaminase. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 902 BP A170 EP A170 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700840 ER PT J AU Keck, T Balcom, JH Antoniu, BA Fernandez-Del-Castillo, C Warshaw, AL AF Keck, T Balcom, JH Antoniu, BA Fernandez-Del-Castillo, C Warshaw, AL TI Matrix metalloproteinase-9 (MMP-9) enhances leukocyte trafficking and alveolar capillary leakage in pancreatitis-associated lung injury by basement membrane digestion SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 598 BP A111 EP A111 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700542 ER PT J AU Kohler, H Rodrigues, SP Maurelli, AT Carlo, E Podolsky, DK McCormick, BA AF Kohler, H Rodrigues, SP Maurelli, AT Carlo, E Podolsky, DK McCormick, BA TI Invasion of Shigella flexneri into model human intestinal epithelia is dependent on a specific lipopolysaccharide interaction with the host cell SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hlth Sci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 371 BP A70 EP A70 DI 10.1016/S0016-5085(01)80348-6 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700347 ER PT J AU Ku, NO Gish, RG Wright, TL Omary, MB AF Ku, NO Gish, RG Wright, TL Omary, MB TI Keratin 8 mutations in patient with cryptogenic liver disease SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Palo Alto VA Med Ctr, Palo Alto, CA USA. Stanford Univ, Palo Alto, CA 94304 USA. Calif Pacific Med Ctr, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 234 BP A45 EP A45 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700220 ER PT J AU Kuo, B Camilleri, M Burton, D Viramontes, BE McKinzie, S Thomforde, GM O'Connor, MK Brinkmann, BH AF Kuo, B Camilleri, M Burton, D Viramontes, BE McKinzie, S Thomforde, GM O'Connor, MK Brinkmann, BH TI 5-HT3 antagonism of upper gastrointestinal symptoms after a dyspepsia-inducing meal SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 714 BP A134 EP A134 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700658 ER PT J AU Kwon, DH Lee, M Kim, JJ Osato, MS El-Zaatari, FAK Graham, DY AF Kwon, DH Lee, M Kim, JJ Osato, MS El-Zaatari, FAK Graham, DY TI Emergence of acquired-multidrug resistant Helicobacter pylori among clinical isolates SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Samsung Med Ctr, Seoul, South Korea. VA Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2616 BP A514 EP A514 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702548 ER PT J AU Lew, EA Risch, HA Chow, WH Gammon, MD Vaughan, TL Schoenberg, JB Stanford, JL Farrow, D West, AB Rotterdam, H Blot, WJ Fraumeni, JF AF Lew, EA Risch, HA Chow, WH Gammon, MD Vaughan, TL Schoenberg, JB Stanford, JL Farrow, D West, AB Rotterdam, H Blot, WJ Fraumeni, JF TI Epidemiological study of risk factors for gastric carcinoids SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Yale Univ, New Haven, CT 06520 USA. NCI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. NYU Med Ctr, New York, NY 10016 USA. Columbia Univ, New York, NY USA. Inst Int Epidemiol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1326 BP A256 EP A256 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701262 ER PT J AU Lew, EA Risch, HA Chow, WH Gammon, MD Vaughan, TL Schoenberg, JB Stanford, JL West, AB Rotterdam, H Blot, WJ Blaser, MJ Fraumeni, JF AF Lew, EA Risch, HA Chow, WH Gammon, MD Vaughan, TL Schoenberg, JB Stanford, JL West, AB Rotterdam, H Blot, WJ Blaser, MJ Fraumeni, JF TI Helicobacter pylori, gastroesophageal reflux, their interrelationships, and the risk of esophageal adenocarcinoma SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Yale Univ, New Haven, CT 06520 USA. Natl Canc Inst, Bethesda, MD USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. NYU Med Ctr, New York, NY 10016 USA. Columbia Univ, New York, NY USA. Int Epidemiol Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 159 BP A31 EP A31 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700150 ER PT J AU Malaty, HM Tanaka, E Kumagai, T Ota, H Akamatsu, ET Kiyosawa, K Graham, DY Katsuyama, T AF Malaty, HM Tanaka, E Kumagai, T Ota, H Akamatsu, ET Kiyosawa, K Graham, DY Katsuyama, T TI A birth cohort study of the seroepidemiologic association of Helicobacter pylori infection and Hepatitis A virus in rural Japan SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Shinshu Univ, Sch Med, Matsumoto, Nagano 390, Japan. VA Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 686 BP A128 EP A128 DI 10.1016/S0016-5085(08)80631-2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700630 ER PT J AU Malaty, HM Graham, DY Elkasabany, A Reddy, SG Srinivasan, SR Berenson, GS AF Malaty, HM Graham, DY Elkasabany, A Reddy, SG Srinivasan, SR Berenson, GS TI Natural history of Helicobacter pylori infection from infancy to adulthood: A 21-year follow-up cohort study SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Tulane Univ, Sch Publ Hlth, New Orleans, LA 70118 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 683 BP A128 EP A128 DI 10.1016/S0016-5085(08)80631-2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700627 ER PT J AU Mason, AC Eloubeidi, MA El-Serag, HB AF Mason, AC Eloubeidi, MA El-Serag, HB TI Temporal trends in survival of patients with esophageal adenocarcinoma in the United States: 1973-1997 SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 155 BP A30 EP A30 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700146 ER PT J AU Mizoguchi, A Mizoguchi, E De Jong, YP Takedatsu, H Preffer, FI Terhorst, C Bhan, AK AF Mizoguchi, A Mizoguchi, E De Jong, YP Takedatsu, H Preffer, FI Terhorst, C Bhan, AK TI Role of CD5 expression on TCR gamma delta T cell-differentiation and development of chronic intestinal inflammation SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2629 BP A517 EP A517 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702561 ER PT J AU Mizoguchi, E Mizoguchi, A Takedatsu, H Cario, E De Jong, YP Ooi, CJ Xavier, RJ Terhorst, CP Podolsky, DK Bhan, AK AF Mizoguchi, E Mizoguchi, A Takedatsu, H Cario, E De Jong, YP Ooi, CJ Xavier, RJ Terhorst, CP Podolsky, DK Bhan, AK TI TNF receptor type II (TNFR2)-mediated colonic epithelial alteration in chronic intestinal inflammation. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 312 BP A59 EP A60 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700293 ER PT J AU Mizoguchi, E Takedatsu, H Hokama, A Imai, Y Tanaka, Y Mizoguchi, A Bhan, AK AF Mizoguchi, E Takedatsu, H Hokama, A Imai, Y Tanaka, Y Mizoguchi, A Bhan, AK TI Development of granulomatous colonic inflammation in absence of B cells and IL-4 in T cell receptor-alpha knockout mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 191 BP A37 EP A38 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700182 ER PT J AU Muza, MM Schneeberger, E Koutsouris, A Hecht, G AF Muza, MM Schneeberger, E Koutsouris, A Hecht, G TI EPEC infection of intestinal epithelial cells induces formation of aberrant tight junction strands in the lateral membrane SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 592 BP A109 EP A110 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700536 ER PT J AU Nguyen, DD Liu, CH Mizoguchi, A Klein, C Takeshima, F Mizoguchi, E Bhan, AK Snapper, SB AF Nguyen, DD Liu, CH Mizoguchi, A Klein, C Takeshima, F Mizoguchi, E Bhan, AK Snapper, SB TI Lymphocytes are necessary and sufficient for colitis development in WASP-deficient mice SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hannover Med Sch, D-3000 Hannover, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2627 BP A516 EP A516 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702559 ER PT J AU Osato, MS Penland, RL Durden, M Graham, DY AF Osato, MS Penland, RL Durden, M Graham, DY TI Novel therapies for Helicobacter pylori infection: Potassium iodide SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2956 BP A582 EP A582 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702886 ER PT J AU Raychowdhury, R Schaefer, G Wang, TC Hoecker, M AF Raychowdhury, R Schaefer, G Wang, TC Hoecker, M TI Activation of Egr-1 is critical for gastrin and PMA dependent transactivation of the chromogranin A promoter in gastric cancer cells SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Charite, Berlin, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1575 BP A305 EP A305 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701511 ER PT J AU Rudolph, RE Dominitz, JA Lampe, JW Levy, L Bronner, MP Potter, JD AF Rudolph, RE Dominitz, JA Lampe, JW Levy, L Bronner, MP Potter, JD TI Magnification chromoendoscopy to identify aberrant crypt foci: A pilot study in humans SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. VA Puget Sound HCS, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3098 BP A610 EP A610 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703028 ER PT J AU Sakaguchi, T Koehler, H Gu, XB McCormick, BA Reinecker, HC AF Sakaguchi, T Koehler, H Gu, XB McCormick, BA Reinecker, HC TI Mechanistic repertoire of Shigella flexneri (Sh.f.) to regulate tight junctional complexes in human intestinal epithelial cells (IEC). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 676 BP A126 EP A126 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700620 ER PT J AU Sakaguchi, T Nishiyama, R Kinugasa, T Gu, XB Macdermott, RP Podolsky, DK Reinecker, HC AF Sakaguchi, T Nishiyama, R Kinugasa, T Gu, XB Macdermott, RP Podolsky, DK Reinecker, HC TI Intestinal barrier function can be regulated by distinct mechanisms modulating transmembrane or intracellular components of tight junctions (TJ). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Albany Med Coll, Albany, NY 12208 USA. NR 0 TC 0 Z9 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3781 BP A701 EP A701 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703483 ER PT J AU Sakaguchi, T Kinugasa, T Nanthakumar, N Gu, XB Reinecker, HC AF Sakaguchi, T Kinugasa, T Nanthakumar, N Gu, XB Reinecker, HC TI The proteasome inhibitor MG-132 reveals novel mechanisms specific for the activation of IL-8 mRNA expression in human intestinal epithelial cells (IEC). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2538 BP A498 EP A499 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702471 ER PT J AU Sands, BE Arsenault, J AF Sands, BE Arsenault, J CA Clin Alliance New England TI Risk of early surgery in Crohn's disease: Implications for early treatment strategies SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2291 BP A449 EP A450 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702226 ER PT J AU Selinger, RRE Norman, S Dominitz, JA AF Selinger, RRE Norman, S Dominitz, JA TI Failure of health care professionals to accurately interpret fecal occult blood tests (FOBT) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3068 BP A604 EP A604 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702998 ER PT J AU Servoss, JC Sherman, KE Robbins, G Liou, SH Reisler, R Polsky, B Murphy, R Theodore, D Miskovsky, E Peters, MG Chung, RT AF Servoss, JC Sherman, KE Robbins, G Liou, SH Reisler, R Polsky, B Murphy, R Theodore, D Miskovsky, E Peters, MG Chung, RT TI Hepatotoxicity in the US adult AIDS clinical trial group SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NIAID, Bethesda, MD 20892 USA. St Lukes Hosp, New York, NY USA. Northwestern Univ, Chicago, IL 60611 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Texas, Galveston, TX 77555 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 283 BP A54 EP A54 DI 10.1016/S0016-5085(08)80265-X PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700264 ER PT J AU Shah, U Dickinson, BL Fusunyan, RD Nanthakumar, N Lencer, W Walker, WA AF Shah, U Dickinson, BL Fusunyan, RD Nanthakumar, N Lencer, W Walker, WA TI The neonatal IgG receptor FcRn, is expressed in the human fetal intestine and the non-malignant fetal intestinal epithelial cell line. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Childrens Hosp, Charlestown, MA USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1563 BP A303 EP A303 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701499 ER PT J AU Shibata, T Takeshima, F Chen, F Alt, FW Snapper, SB AF Shibata, T Takeshima, F Chen, F Alt, FW Snapper, SB TI The role of Cdc42 in the invasion and the actin-based motility of Shigella flexneri SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU 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 APR PY 2001 VL 120 IS 5 SU 1 MA 1666 BP A323 EP A323 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701602 ER PT J AU Sinclair, NF McLauhglin, JT Raychowdhury, R Koh, TJ AF Sinclair, NF McLauhglin, JT Raychowdhury, R Koh, TJ TI Gastrin activates the human HB-EGF promoter via the MAP kinase signaling pathway through a GC rich gastrin response element SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1590 BP A308 EP A308 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701526 ER PT J AU Stockwell, DH Woo, P Jacobson, BC Syngal, S Remily, RM Wolf, J Farraye, FA AF Stockwell, DH Woo, P Jacobson, BC Syngal, S Remily, RM Wolf, J Farraye, FA TI Rates of Colorectal Cancer screening in women undergoing mammography increase with knowledge of the adenoma-carcinoma sequence SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Faulkner Hosp, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3072 BP A605 EP A605 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703002 ER PT J AU Strate, LL Davis, R Schnipper, J Syngal, S AF Strate, LL Davis, R Schnipper, J Syngal, S TI The impact of timing of colonoscopy on length of hospital stay in patients with acute lower gastrointestinal bleeding SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2068 BP A404 EP A404 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702003 ER PT J AU Stylopoulos, N Rattner, DW AF Stylopoulos, N Rattner, DW TI The development of achalasia secondary to laparoscopic Nissen fundoplication SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 229 BP A44 EP A44 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700215 ER PT J AU Sung, JY Lau, JY Chan, FK Graham, DY AF Sung, JY Lau, JY Chan, FK Graham, DY TI How often are endoscopic ulcers in NSAID trials diagnosed as actual ulcers by experienced endoscopists? SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Chinese Univ Hong Kong, Hong Kong, Hong Kong. VA Med Ctr, Houston, TX USA. NR 0 TC 5 Z9 5 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 APR PY 2001 VL 120 IS 5 SU 1 MA 3034 BP A597 EP A597 DI 10.1016/S0016-5085(08)82971-X PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702964 ER PT J AU Suzuki, M Podolsky, DK AF Suzuki, M Podolsky, DK TI Differential regulation of Toll-like receptors by pro- and anti-inflammatory cytokines between human intestinal epithelial and monocytic cell lines. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1684 BP A326 EP A326 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701620 ER PT J AU Takeshima, F Shibata, T Chen, F Liu, CH Nguyen, DD Alt, FW Snapper, SB AF Takeshima, F Shibata, T Chen, F Liu, CH Nguyen, DD Alt, FW Snapper, SB TI An essential role for N-WASP, but not Cdc42, in EPEC induced pedestal formation SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 675 BP A126 EP A126 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700619 ER PT J AU Tavakkolizadeh, A Stephen, AE Kaihara, S Mooney, DL Kim, BS Ashley, SW Vacanti, JP Whang, EE AF Tavakkolizadeh, A Stephen, AE Kaihara, S Mooney, DL Kim, BS Ashley, SW Vacanti, JP Whang, EE TI Tissue engineered intestine: Morphology and enterocyte dynamics SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 404 BP A75 EP A75 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700369 ER PT J AU Tsuzuki, Y Fukumura, D Jain, RK AF Tsuzuki, Y Fukumura, D Jain, RK TI Tumor-host interaction modulates production of antiangiogenic factors from human pancreatic cancer SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 20 BP A4 EP A5 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700021 ER PT J AU Valentine, JF Randall, M Lauwers, GY Grisham, MB AF Valentine, JF Randall, M Lauwers, GY Grisham, MB TI Intramuscular injection of a recombinant adeno-associated virus (rAAV) vector containing interleukin-10 (IL-10) reduces proximal colonic inflammation in IL-10 deficient mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Florida, Dept Med, Malcom Randall VAMC, Gainesville, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Louisiana State Univ, Med Ctr, Dept Mol & Cell Physiol, Shreveport, LA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3720 BP A689 EP A689 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703422 ER PT J AU Whary, MT Shi, HN White, H Nagler-Anderson, C Fox, JG AF Whary, MT Shi, HN White, H Nagler-Anderson, C Fox, JG TI Th2 responses to the Helminth Heligmosomoides polygyrus reduce Th1-promoted epithelial hyperplasia in a mouse model of Helicobacter hepaticus-associated inflammatory bowel disease (IBD) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1019 BP A194 EP A194 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700957 ER PT J AU Woo, P Stockwell, D Jacobson, B Remily, R Syngal, S Farraye, F Wolf, J AF Woo, P Stockwell, D Jacobson, B Remily, R Syngal, S Farraye, F Wolf, J TI Colorectal cancer screening in women: The role of the primary care provider in determining screening behavior SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Faulkner Hosp, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3067 BP A604 EP A604 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702997 ER PT J AU Zhang, XB Gaspard, JP Chung, DC AF Zhang, XB Gaspard, JP Chung, DC TI VEGF is regulated by the WNT pathway in colon cancer SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 19 BP A4 EP A4 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700020 ER PT J AU Nietsch, H Dominitz, JA AF Nietsch, H Dominitz, JA TI Post-polypectomy hemorrhage in von Willebrand disease SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID VONWILLEBRANDS-DISEASE; DDAVP C1 VA Puget Sound Hlth Care Syst, Seattle Div 111 S Gastro, Seattle, WA 98108 USA. Washington Univ, Sch Med, Div Gastroenterol, Dept Med, Seattle, WA USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div 111 S Gastro, 660 S Columbian Way, Seattle, WA 98108 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 16 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 4 BP 531 EP 533 DI 10.1067/mge.2001.112714 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 418TY UT WOS:000167908500032 PM 11275907 ER PT J AU Ayub, K AF Ayub, K TI EUS guided superior hypogastric plexus neurolysis: A new technique for the management of pelvic pain SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 3421 BP AB113 EP AB113 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800200 ER PT J AU Bounds, BC Brugge, WR AF Bounds, BC Brugge, WR TI EUS guided fine needle aspiration cytology and tumor marker analysis of pancreatic ductal fluid differentiates between IPMT and chronic pancreatitis. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 4185 BP AB163 EP AB163 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800373 ER PT J AU Brugge, WR Saltzman, JR Scheiman, JM Wallace, MB Jowell, PS Pochapin, MB Chak, A Stevens, PD Gress, FG Lewandrowski, K AF Brugge, WR Saltzman, JR Scheiman, JM Wallace, MB Jowell, PS Pochapin, MB Chak, A Stevens, PD Gress, FG Lewandrowski, K TI Diagnosis of cystic neoplasms of the pancreas by EUS: The report of the cooperative pancreatic cyst study. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Duke Univ, Sch Med, Durham, NC USA. New Hosp, New York, NY USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Columbia Presbyterian Hosp, New York, NY USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. NR 0 TC 8 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 573 BP AB71 EP AB71 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800054 ER PT J AU Jensen, DM Kovacs, TO Jutabha, R Gralnek, IM Dulai, GS Machicado, GA AF Jensen, DM Kovacs, TO Jutabha, R Gralnek, IM Dulai, GS Machicado, GA TI Prospective study of delayed post-polypectomy bleeding compared to other causes of severe hematochezia SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 4249 BP AB182 EP AB182 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800437 ER PT J AU Jensen, DM Machicado, GA Hirabayashi, K AF Jensen, DM Machicado, GA Hirabayashi, K TI Double blind randomized controlled study of polysaccharide gel compared to glue & other sclerosants for obliteration of large veins SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Heallthcare Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 4164 BP AB157 EP AB157 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800352 ER PT J AU Jensen, DM Machicado, GA Hirabayashi, K AF Jensen, DM Machicado, GA Hirabayashi, K TI Randomized double blind study of polysaccharide gel compared to other agents for endoscopic hemostasis of bleeding canine esophageal varices SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 4127 BP AB147 EP AB147 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800315 ER PT J AU Lai, RW Wiersema, MJ Sahai, A Chak, A Chang, KJ Kochman, ML Wallace, MB Palazzo, L Brugge, WR Mishra, G Vilmann, P Bounds, BC Catalano, M Mallery, S AF Lai, RW Wiersema, MJ Sahai, A Chak, A Chang, KJ Kochman, ML Wallace, MB Palazzo, L Brugge, WR Mishra, G Vilmann, P Bounds, BC Catalano, M Mallery, S TI Blinded comparison of linear and radial endoscopic ultrasound (EUS) for the evaluation of chronic pancreatitis (CP) SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Mayo Clin, Rochester, MN USA. Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Chao Family Clin Canc Res Ctr, Orange, CA USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Beaujon Hosp, Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Florida, Gainesville, FL USA. Gentofte Hosp, Hellerup, Denmark. GI Consultants Ltd, Milwaukee, WI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 4208 BP AB170 EP AB170 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800396 ER PT J AU Mokhashi, MS Glenn, TF Jost, C Wallace, MB Kim, CY Johnson, RH Gumustop, B Cotton, PB Hawes, RH AF Mokhashi, MS Glenn, TF Jost, C Wallace, MB Kim, CY Johnson, RH Gumustop, B Cotton, PB Hawes, RH TI A 4-minute unsedated office based screening esophagoscopy for Barrett's. A blinded prospective comparative study of diagnostic accuracy and tolerance of esophagoscopy with a battery powered esophagoscope (BPE) with a sedated standard video-endoscopy (SVE). SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 328 BP AB62 EP AB62 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800024 ER PT J AU Poneros, JM Tearney, GJ Bouma, BE Lauwers, GY Nishioka, NS AF Poneros, JM Tearney, GJ Bouma, BE Lauwers, GY Nishioka, NS TI Diagnosis of dysplasia in Barrett's esophagus using optical coherence tomography SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 3420 BP AB113 EP AB113 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800199 ER PT J AU Poneros, JM Shishkov, M Tearney, GJ Kelsey, PB Lauwers, GY Nishioka, NS Bouma, BE AF Poneros, JM Shishkov, M Tearney, GJ Kelsey, PB Lauwers, GY Nishioka, NS Bouma, BE TI Optical coherence tomography of the biliary tree during ERCP SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 3320 BP AB84 EP AB84 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800099 ER PT J AU Qureshi, MA Heiser, M Anand, BS AF Qureshi, MA Heiser, M Anand, BS TI Do the number of polyps seen at flexible sigmoidoscopy predict polyp numbers at colonoscopy? SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2001 VL 53 IS 5 SU S MA 4278 BP AB190 EP AB190 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429XG UT WOS:000168542800466 ER PT J AU Bogdanov, A Tung, CH Bredow, S Weissleder, R AF Bogdanov, A Tung, CH Bredow, S Weissleder, R TI DNA binding chelates for nonviral gene delivery imaging SO GENE THERAPY LA English DT Article DE gene delivery; nuclear imaging; chelate; technetium; expression vector ID GREEN FLUORESCENT PROTEIN; PLASMID DNA; PHASE-I; THERAPY; EXPRESSION; CANCER; MECHANISM; SYSTEMS; HYBRIDIZATION; PROSPECTS AB Noninvasive in vivo monitoring of gene delivery would provide a critically important information regarding the spatial distribution, local concentration, kinetics of removal and/or biodegradation of the expression vector. We developed a novel approach to noninvasive gene delivery imaging using heterobifunctional peptide-based chelates (PBC) bearing double-stranded DNA-binding groups and a technetium-binding amino acid motif. One of such chelates: Gly-Cys (Acm)-Gly-Cys(Acm)-Gly-Lys(4)-Lys-(N-epsilon-[4-(psoralen-8-yloxy)]butyrate)-NH2 has been characterized and labeled with reduced Tc-99m pertechnetate (oxotechnetate). The psoralen moiety (a DNA binding group of PBC) allowed linking to double-stranded DNA upon short-term irradiation with the near UV range light (>320 nm). Approximately 30-40% of added Tc-99m-labeled PBC was nonextractable and coeluted with a model pCMV-GFP vector during the gel-permeation chromatography. Nuclear imaging of 'naked' DNA and DNA complexes with lipid-based transfection reagents ('lipoplexes') has been performed after systemic or local administration of Tc-99m-PBC-labeled DNA in mice. Imaging results were corroborated with the biodistribution using (TC)-T-99m-PBC and P-32-labeled DNA and lipoplexes. A markedly different biodistribution of Tc-99m PBC-labeled DNA and lipoplexes was observed with the latter being rapidly trapped in the liver, spleen and lung. Tc-99m PBC-DNA was used as an imaging tracer during in vivo transfection of B16 melanoma by local injection of 'naked' Tc-99m PBC-DNA and corresponding lipoplexes. As demonstrated by nuclear imaging, Tc-99m PBC-DNA lipoplexes showed a slower elimination from the site of injection than Tc-99m PBC-DNA alone. This result correlated with a higher expression of marker mRNA and green fluorescent protein as determined using RT-PCR and immunohistochemistry, respectively. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Room 5420,Bldg 149,13th St, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [5RO1 CA74424-01]; NIDDK NIH HHS [1R21 DK55713-01]; NINDS NIH HHS [5RO1 NS35258-03] NR 41 TC 19 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 2001 VL 8 IS 7 BP 515 EP 522 DI 10.1038/sj.gt.3301410 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 419PQ UT WOS:000167958000003 PM 11319618 ER PT J AU Dal Cin, P Atkins, L Ford, C Ariyanayagam, S Armstrong, SA George, R Cleary, A Morton, CC AF Dal Cin, P Atkins, L Ford, C Ariyanayagam, S Armstrong, SA George, R Cleary, A Morton, CC TI Amplification of AML1 in childhood acute lymphoblastic leukemias SO GENES CHROMOSOMES & CANCER LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TRISOMY-21; CHROMOSOME-21 AB Amplification of AML1 has been confirmed by fluorescence in situ hybridization analysis in two cases of childhood acute lymphoblastic leukemia. It remains to be elucidated whether this amplification results in up-regulation of the normal AML I gene product or a potentially mutant AML1 transcript. (C) 2001 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Hematol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Dal Cin, P (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 17 TC 40 Z9 40 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD APR PY 2001 VL 30 IS 4 BP 407 EP 409 DI 10.1002/1098-2264(2001)9999:9999<::AID-GCC1107>3.0.CO;2-C PG 3 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 407LJ UT WOS:000167272800010 PM 11241794 ER PT J AU Crispino, JD Lodish, MB Thurberg, BL Litovsky, SH Collins, T Molkentin, JD Orkin, SH AF Crispino, JD Lodish, MB Thurberg, BL Litovsky, SH Collins, T Molkentin, JD Orkin, SH TI Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors SO GENES & DEVELOPMENT LA English DT Article DE GATA-4; FOG cofactor; coronary vasculature; heart ID TRANSCRIPTION FACTOR; VENTRAL MORPHOGENESIS; CARDIAC DEVELOPMENT; TARGETED MUTATION; TUBE FORMATION; MICE; DIFFERENTIATION; PROTEIN; CLONING AB GATA-family transcription factors are critical to the development of diverse tissues. In particular, GATA-4 has been implicated in formation of the vertebrate heart, As the mouse Gata-4 knock-out is early embryonic lethal because of a defect in ventral morphogenesis, the in vivo function of this factor in heart development remains unresolved. To search for a requirement for Gata4 in heart development, we created mice harboring a single amino acid replacement in GATA-4 that impairs its physical interaction with its presumptive cardiac cofactor FOG-2. Gata4(ki/ki) mice die just after embryonic day (E) 12.5 exhibiting features in common with Fog2(-/-) embryos as well as additional semilunar cardiac valve defects and a double-outlet right ventricle. These findings establish an intrinsic requirement for GATA-4 in heart development. We also infer that GATA-4 function is dependent on interaction with FOG-2 and, very likely, an additional FOG protein for distinct aspects of heart formation. C1 Univ Cincinnati, Childrens Hosp, Cincinnati, OH 45229 USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Med Sch, Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Univ Cincinnati, Childrens Hosp, Cincinnati, OH 45229 USA. OI Crispino, John/0000-0002-8182-8306 NR 32 TC 212 Z9 217 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2001 VL 15 IS 7 BP 839 EP 844 DI 10.1101/gad.875201 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 422RU UT WOS:000168133700004 PM 11297508 ER PT J AU Amann, ST Gates, LK Aston, CE Pandya, A Whitcomb, DC AF Amann, ST Gates, LK Aston, CE Pandya, A Whitcomb, DC TI Expression and penetrance of the hereditary pancreatitis phenotype in monozygotic twins SO GUT LA English DT Article DE hereditary pancreatitis; genetic; twins; penetrance; trypsinogen ID CATIONIC TRYPSINOGEN GENE; MUTATIONS; FAMILY; MAPS AB Background-Hereditary pancreatitis (HP) is a rare autosomal dominant disorder with variable expression and an overall lifetime penetrance of 80%. We hypothesised that (1) monozygotic twins within similar environments would develop the typical signs of HP at a similar age, and (2) if penetrance were due to modifier genes or environment, all twin pairs would be concordant for expression of HP. Aim-Identify monozygotic twins with HP and determine the penetrance, concordance, and age of onset of symptoms. Methods-Twins from HP kindreds were identified from the Midwest Multicenter Pancreatic Study group database, referrals, and literature searches. Each twin set was assessed for phenotypic expression, concordance, and difference in age of phenotypic onset of pancreatitis. The difference in onset of symptoms for symptomatic affected non-twin sibling pairs as well as non-twin pairs that were mutation, sex, and age matched were calculated as two comparison groups. Results-Seven of 11 monozygotic pairs identified were suitable for evaluation and four were concordant for pancreatitis. Forty eight affected sibling pairs and 33 pairs of mutation, sex, and age matched (cationic trypsinogen R122H (30 pairs) and N29I (three pairs)) subjects were identified for comparison groups. The median (quartiles Q1, Q3) difference in the age of phenotypic onset in the concordant twins was 1 (0, 2.4) years, 2 (1, 6) for the affected siblings, and 7 (2, 15) years in the comparison control group. Three of the seven sets of twins (43%) were discordant for phenotypic expression of pancreatitis. The overall penetrance in the seven pairs of monozygotic twins was 78.6%. Conclusions-Genetic and/or environmental factors contribute to expression and age of onset of HP. Nuclear genes or general environmental factors alone cannot explain the 80% penetrance. Determining the mechanism of non-penetrance may help in developing a strategy to prevent the phenotypic expression of pancreatitis in individuals with an underlying genetic predisposition. C1 Univ Florida, Dept Med, Div Gastroenterol Hepatol & Nutr, Gainesville, FL 32610 USA. Univ Kentucky, Med Ctr, Lexington, KY 40536 USA. Univ Pittsburgh, Ctr Gen Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15240 USA. RP Amann, ST (reprint author), N Mississippi Med Ctr, Pancreat Serv, POB 21, Tupelo, MS 38802 USA. FU NIAAA NIH HHS [AA10885]; NIDDK NIH HHS [DK51954] NR 29 TC 34 Z9 34 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2001 VL 48 IS 4 BP 542 EP 547 DI 10.1136/gut.48.4.542 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 413NU UT WOS:000167619300020 PM 11247900 ER PT J AU Boruta, DM Schorge, JO Duska, LA Crum, CP Castrillon, DH Sheets, EE AF Boruta, DM Schorge, JO Duska, LA Crum, CP Castrillon, DH Sheets, EE TI Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT Meeting of the New-England-Association-of-Gynecologic-Oncologists CY JUN 09-11, 2000 CL LENOX, MASSACHUSETTS SP New England Assoc Gynecol Oncol ID SMALL-CELL CARCINOMA; ADJUVANT CHEMOTHERAPY; LUNG-CANCER; CISPLATIN; ETOPOSIDE; DOXORUBICIN; TUMORS; CYCLOPHOSPHAMIDE; VINCRISTINE; ALTERNATION AB Objective. Patients with early-stage neuroendocrine cervical carcinoma (NECC) have a high mortality rate despite aggressive therapy. The rarity of this tumor precludes initiation of a randomized, prospective trial. We reviewed our experience in early stage disease and performed a meta-analysis of the literature to identify prognostic factors and determine optimal multimodality therapy. Methods. Eleven women with International Federation of Gynecology and Obstetrics (FIGO) early stage (IB-IIA) NECC were treated with surgery and chemotherapy at our institutions between 1978 and 1998, Administration of radiation therapy was recorded, but not required for inclusion in this study. A gynecologic pathologist reviewed all histopathologic sections. Medical records were retrospectively reviewed and clinical data obtained. Twenty-three early-stage NECC patients who were similarly treated during the study interval were identified by a Medline search of the English literature and included in the analysis. The Kaplan-Meier method and log-rank test were used for survival analysis. Results. The overall 2-year survival rate for the 34 patients was 38%. The median age was 37 years (range, 20-75 years). Median cervical tumor diameter was 3.2 cm (range 0.5-11.0 cm), Lymphovascular space invasion was present in 21 (78%) of 27 patients (7 unknown). Fifteen (52%) of twenty-nine had lymph node metastases (5 unknown). Fifteen patients received postoperative platinum/etoposide (PE), seven received vincristine/adriamycin/cyclophosphamide (VAC), two received alternating cycles of VAC and PE, and ten received other chemotherapy regimens. Twenty women were treated with radiation therapy. The presence of lymph node metastases was a poor prognostic factor (P < 0.001), PE and VAC chemotherapy was associated with increased survival (P < 0.01). Conclusion. NECC is a highly lethal variant of cervical cancer. The presence of lymph node metastases is the most important prognostic variable. Postoperative VAC or PE appears most likely to improve chances for survival, (C) 2001 Academic Press. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Sheets, EE (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. NR 23 TC 47 Z9 50 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2001 VL 81 IS 1 BP 82 EP 87 DI 10.1006/gyno.2000.6118 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 425AQ UT WOS:000168266500015 PM 11277655 ER PT J AU Bristow, RE Duska, LR Montz, FJ AF Bristow, RE Duska, LR Montz, FJ TI The role of cytoreductive surgery in the management of stage IV uterine papillary serous carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE uterine papillary serous carcinoma; surgery; cytoreduction ID EPITHELIAL OVARIAN-CARCINOMA; LONG-TERM SURVIVAL; ENDOMETRIAL CARCINOMA; NEOADJUVANT CHEMOTHERAPY; SURGICAL CYTOREDUCTION; ADENOCARCINOMA; CANCER; UPSC; CYCLOPHOSPHAMIDE; IRRADIATION AB Objective. The aim of this study was to evaluate the survival impact of cytoreductive surgery and other prognostic determinants in patients with Stage IV uterine papillary serous carcinoma (UPSC). Methods. All patients with PICO Stage IV UPSC diagnosed between January 1, 1989 and December 31, 1998 were identified from tumor registry databases. Individual patient data were collected retrospectively. Survival analysis and comparisons were performed using the method of Kaplan and Meier, the log-rank test, and the Cox proportional hazards regression model. Predictors of surgical outcome were evaluated using the log-rank test. Results. Thirty-one patients underwent primary cytoreductive surgery for Stage IV UPSC (median age, 65 years). The median survival for all patients was 14.4 months. Optimal cytoreduction was defined as residual disease less than or equal to1 cm in maximal diameter. The only significant predictor of a suboptimal surgical outcome was the presence of disease in three or more anatomic regions. Overall, 16 of 31 patients (51.6%) completed primary surgery with optimal disease status. Optimal cytoreduction was associated with a median survival of 26.2 months, compared with 9.6 months for patients left with suboptimal residual disease (P < 0.001). At 24 months, 57.1% of optimally cytoreduced patients were still alive, compared with just 6.7% of patients left with suboptimal disease. Furthermore, patients with only microscopic residual tumor had a significantly longer median survival (30.4 months) than both patients with 0.1- to 1.0-cm residual disease (20.5 months) and those left with suboptimal disease (P = 0.004). Postoperative platinum-based chemotherapy was associated with a median survival of 17.1 months, compared with 9.5 months without such therapy (P = 0.018). Patients receiving the combination of platinum + paclitaxel had a median survival rate of 29.1 months versus 14.4 months for patients receiving platinum + cyclophosphamide +/- doxorubicin (P = 0.054). On multivariate analysis, the only statistically significant predictor of survival was the cytoreductive surgical outcome. Conclusions. The strongest predictor of overall survival for patients with Stage IV UPSC was the amount of residual disease following surgery. Recommended management for this group of patients should consist of maximal surgical cytoreduction followed by platinum-based chemotherapy, preferably in combination with paclitaxel. (C) 2001 Academic Press. C1 Johns Hopkins Med Inst, Dept Gynecol & Obstet, Kelly Gynecol Oncol Serv, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Div Gynecol Oncol, Boston, MA 02114 USA. RP Bristow, RE (reprint author), Johns Hopkins Med Inst, Dept Gynecol & Obstet, Kelly Gynecol Oncol Serv, 600 N Wolfe St,Phipps 248, Baltimore, MD 21287 USA. NR 42 TC 50 Z9 54 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2001 VL 81 IS 1 BP 92 EP 99 DI 10.1006/gyno.2000.6110 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 425AQ UT WOS:000168266500017 PM 11277657 ER PT J AU Chawla, AK Willett, CG AF Chawla, AK Willett, CG TI Squamous cell carcinoma of the anal canal and anal margin SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; COMBINED-MODALITY THERAPY; HUMAN PAPILLOMAVIRUS DNA; DOSE RADIATION-THERAPY; HIV-POSITIVE PATIENTS; EPIDERMOID CARCINOMA; MITOMYCIN-C; INTRAEPITHELIAL LESIONS; CHEMORADIATION THERAPY; HUMAN-IMMUNODEFICIENCY AB Squamous cell carcinomas of the anal canal and margin are relatively uncommon neoplasms of the distal gastrointestinal tract and surrounding skin. The major risk factors for tumor development have been defined through various epidemiologic studies. Randomized, phase III trials have defined the standard of care for anal cancer tumors to be a combined modality approach of radiation therapy and chemotherapy. This nonsurgical, organ-sparing regimen results in good anal sphincter function in the majority of patients, and treatment efficacy is favorable when compared with historic surgical series. Anal margin tumors are staged and treated as skin cancers, with a more favorable prognosis. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02114 USA. RP Willett, CG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, 55 Fruit St, Boston, MA 02114 USA. NR 88 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2001 VL 15 IS 2 BP 321 EP + DI 10.1016/S0889-8588(05)70215-X PG 25 WC Oncology; Hematology SC Oncology; Hematology GA 434GR UT WOS:000168807200008 PM 11370496 ER PT J AU Brown, AL Zietman, AL Shipley, WU Kaufman, DS AF Brown, AL Zietman, AL Shipley, WU Kaufman, DS TI An organ-preserving approach to muscle-invading transitional cell cancer of the bladder SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID CISPLATIN-BASED CHEMOTHERAPY; COMBINED-MODALITY THERAPY; 5-YEAR FOLLOW-UP; QUALITY-OF-LIFE; RADICAL CYSTECTOMY; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; SPARING TREATMENT; PROSPECTIVE TRIAL AB Bladder-preserving treatment for muscle-invasive disease is based on the response of the tumor to induction combined modality therapy. in the future, an organ-conserving approach will be widely offered as a safe and reasonable alternative to radical cystectomy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Brown, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 3,100 Bloosom St, Boston, MA 02114 USA. NR 63 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2001 VL 15 IS 2 BP 345 EP + DI 10.1016/S0889-8588(05)70216-1 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA 434GR UT WOS:000168807200009 PM 11370497 ER PT J AU Munzenrider, JE AF Munzenrider, JE TI Uveal melanomas - Conservation treatment SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID PROTON-BEAM IRRADIATION; RELATIVE BIOLOGICAL EFFECTIVENESS; SURVIVAL FOLLOWING ENUCLEATION; CHOROIDAL MELANOMA; PLAQUE RADIOTHERAPY; RADIATION-THERAPY; CILIARY BODY; TRANSPUPILLARY THERMOTHERAPY; MALIGNANT-MELANOMA; OCULAR MELANOMA AB This article addresses clinical trials and conservation treatments associated with uveal melanoma-the most common adult ocular tumor. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Munzenrider, JE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. NR 67 TC 22 Z9 29 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2001 VL 15 IS 2 BP 389 EP + DI 10.1016/S0889-8588(05)70219-7 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA 434GR UT WOS:000168807200012 PM 11370500 ER PT J AU Fernandez-Santos, JM Utrilla, JC Conde, E Hevia, A Loda, M Martin-Lacave, I AF Fernandez-Santos, JM Utrilla, JC Conde, E Hevia, A Loda, M Martin-Lacave, I TI Decrease in calcitonin and parathyroid hormone mRNA levels and hormone secretion under long-term hypervitaminosis D-3 in rats SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE vitamin D-3; calcitonin; PTH; C cells; parathyroid cells; hypercalcemia ID VITAMIN-D METABOLITES; MESSENGER RIBONUCLEIC-ACID; C-CELLS; PREPROPARATHYROID HORMONE; GENE-TRANSCRIPTION; STORAGE GRANULES; SERUM-CALCIUM; RNA; HYPERCALCEMIA; INVIVO AB In calcium homeostasis, vitamin D-3 is a potent serum calcium-raising agent which in vivo regulates both calcitonin (CT) and parathyroid hormone (PTH) gene expression. Serum calcium is the major secretagogue for CT, a hormone product whose biosynthesis is the main biological activity of thyroid C-cells. Taking advantage of this regulatory mechanism, long-term vitamin D-3-induced hypercalcemia has been extensively used as a model to produce hyperactivation, hyperplasia and even proliferative lesions of C-cells, supposedly to reduce the sustained high calcium serum concentrations. We have recently demonstrated that CT serum levels did not rise after long-term hypervitaminosis D-3. Moreover, C-cells did not have a proliferative response, rather a decrease in CT-producing C-cell number was observed. In order to confirm the inhibitory effect of vitamin D-3 on C-cells, Wistar rats were administered vitamin D-3 chronically (25,000 IU/d) with or without calcium chloride (CaCl2). Under these long-term vitaminD(3)-hypercalcemic conditions, calcium, active metabolites of vitamin D-3, CT and PTH serum concentrations were determined by RIA; CT and PTH mRNA levels were analysed by Northern blot and in situ hybridization; and, finally, the ultrastructure of calciotrophic hormone-producing cells was analysed by electron microscopy. Our results show, that, in rats, long term administration of vitamin D-3 results in a decrease in hormone biosynthetic activities of both PTH and CT-producing cells, albeit at different magnitudes. Based upon these results, we conclude that hypervitaminosis D-3-based methods do not stimulate C-cell activity and can not be used to induce proliferative lesions of calcitonin-producing cells. C1 Univ Sevilla, Fac Med, Dept Citol & Histol Normal & Patol, Sch Med, E-41009 Seville, Spain. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Martin-Lacave, I (reprint author), Univ Sevilla, Fac Med, Dept Citol & Histol Normal & Patol, Sch Med, Av Sanchez Pizjuan S-N, E-41009 Seville, Spain. OI Utrilla, Jose Carmelo/0000-0001-5438-604X; Conde Amiano, Esperanza/0000-0003-3928-0110; Martin-Lacave, Ines/0000-0003-4645-0755; Fernandez-Santos, Jose Maria/0000-0003-4541-1033 NR 31 TC 4 Z9 5 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD APR PY 2001 VL 16 IS 2 BP 407 EP 414 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 421LC UT WOS:000168065000008 PM 11332696 ER PT J AU Lam, PYP Breakefield, XO AF Lam, PYP Breakefield, XO TI Potential of gene therapy for brain tumors SO HUMAN MOLECULAR GENETICS LA English DT Review ID HERPES-SIMPLEX VIRUS; ADENOVIRUS-MEDIATED TRANSFER; ENDOTHELIAL GROWTH-FACTOR; HUMAN-MALIGNANT GLIOMA; NEURAL STEM-CELLS; THYMIDINE KINASE GENES; VECTOR-PRODUCER CELLS; NERVOUS-SYSTEM TUMORS; HSV-TK GENE; IN-VITRO AB Brain tumors comprise a broad spectrum of biological and clinical entities making it unlikely for any single therapeutic approach to be universally applicable. In particular, malignant glioblastoma multiforme have defied all current therapeutic modalities. Gene therapy offers the potential to augment current neurosurgical, radiation and drug treatments with little increase in morbidity, Many therapeutic transgenes have shown efficacy in experimental models, including generation of toxic compounds, enzymatic activation of pro-drugs, expression of tumor suppressor or apoptotic proteins, inhibition of angiogenesis and enhancement of immune responses to tumor antigens, Vectors have been used as gene delivery vehicles and as cytotoxic agents in their own right by selective replication and lysis of tumor cells, thereby also generating vectors onsite. Brain tumors appear to offer some 'Achilles' heels' in that they are usually contained within the brain and represent a unique dividing cell population there. However, the heterogeneous and invasive characteristics of these tumor cells, as well as sequestration of tumor antigens within a relatively immune privileged location present serious problems for effective therapy. This review will focus on current transgene/vector strategies, including novel therapeutic genes, combinational therapies and new delivery modalities, the latter of which appears to be the rate limiting factor for gene therapy of brain tumors in humans. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. Natl Canc Ctr, Div Mol & Cellular Res, Singapore 169610, Singapore. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Mol Neurogenet, 13th St,Bldg 149, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69246]; NINDS NIH HHS [NS24279] NR 164 TC 48 Z9 50 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR PY 2001 VL 10 IS 7 SI SI BP 777 EP 787 DI 10.1093/hmg/10.7.777 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 424GH UT WOS:000168224100018 PM 11257112 ER PT J AU Montgomery, E Bronner, MP Goldblum, JR Greenson, JK Haber, MM Hart, J Lamps, LW Lauwers, GY Lazenby, AJ Lewin, DN Robert, ME Toledano, AY Shyr, Y Washington, K AF Montgomery, E Bronner, MP Goldblum, JR Greenson, JK Haber, MM Hart, J Lamps, LW Lauwers, GY Lazenby, AJ Lewin, DN Robert, ME Toledano, AY Shyr, Y Washington, K TI Reproducibility of the diagnosis of dysplasia in Barrett esophagus: A reaffirmation SO HUMAN PATHOLOGY LA English DT Article DE Barrett esophagus; dysplasia; interobserver; variability ID PHOTODYNAMIC THERAPY; SPECIALIZED MUCOSA; ADENOCARCINOMA; REDUCTION; ABLATION; CANCER AB Morphologic assessment of dysplasia in Barrett esophagus, despite limitations, remains the basis of treatment. We rigorously tested modified 1988 criteria, assessing intraobserver and interobserver reproducibility. Participants submitted slides of Barrett mucosa negative (BE) and indefinite (IND) for dysplasia, with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and with carcinoma. Two hundred fifty slides were divided into 2 groups. The first 125 slides were reviewed, without knowledge of the prior diagnoses, on 2 occasions by 12 gastrointestinal pathologists without prior discussion of criteria. Results were analyzed by kappa statistics, which correct for agreement by chance. A consensus meeting was then held, establishing, by group review of the index 125 slides, the criteria outlined herein. The second 125-slide set,vas then reviewed twice by each of the same 12 pathologists, and follow-up kappa statistics were calculated. When statistical analysis was performed using 2 broad diagnostic categories (BE, IND, and LG v HG and carcinoma), intraobserver agreement was near perfect both before and after the consensus meeting (mean kappa = 0.82 and 0.80). Interobserver agreement was substantial (kappa = 0.66) and improved after the consensus meeting (kappa = 0.70; P =.02). When statistical analysis was performed using 4 clinically relevant separations (BE; IND and LCD; HGD; carcinoma), mean intraobserver kappa improved from 0.64 to 0.68 (both substantial) after the consensus meeting, and mean interobserver kappa improved from 0.43 to 0.46 (both moderate agreement). When statistical analysis was performed using 4 diagnostic categories that required distinction between LGD and IND (BE; IND; LGD; HGD and carcinoma), the pre-consensus meeting mean intraobserver kappa was 0.60 (substantial agreement), improving to 0.65 after the meeting (P <.05). Interobserver agreement was poorer, with premeeting and postmeeting mean values unchanged ( = 0.43 at both times). Interobserver agreement was substantial for HGD/carcinoma (kappa = 0.65) moderate to substantial for BE (kappa = 0.58), fair for LGD (kappa = 0.32), and slight for IND (kappa = 0.15). The intraobserver reproductibility for the diagnosis of dysplasia in BE was substantial. Interobserver reproducibility was substantial at the ends of the spectrum (BE and HG/carcinoma) but slight for IND. Both intraobserver and interobserver variation improved overall after the application of a modified grading system developed at a consensus conference but not in separation of BE, IND, and LGD. The criteria used by the group are presented. C1 Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. MCP Hahnemann Univ, Dept Pathol, Philadelphia, PA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. Yale Univ, Dept Pathol, New Haven, CT 06520 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Arkansas, Little Rock, AR 72204 USA. Vanderbilt Univ, Dept Pathol, Nashville, TN USA. Vanderbilt Univ, Dept Prevent Med & Biostat, Nashville, TN USA. RP Montgomery, E (reprint author), Johns Hopkins Univ, Dept Pathol, Ross 632,720 Rutland Ave, Baltimore, MD 21205 USA. NR 14 TC 454 Z9 461 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 2001 VL 32 IS 4 BP 368 EP 378 DI 10.1053/hupa.2001.23510 PG 11 WC Pathology SC Pathology GA 427FX UT WOS:000168395100003 PM 11331953 ER PT J AU Sykes, M AF Sykes, M TI Mixed chimerism and transplant tolerance SO IMMUNITY LA English DT Review ID BONE-MARROW CHIMERAS; NATURAL-KILLER-CELLS; NONLETHAL PREPARATIVE REGIMEN; HEMATOPOIETIC STEM-CELLS; LONG-TERM SURVIVAL; LARGE-ANIMAL-MODEL; CLASS II+ CELLS; T-CELLS; COSTIMULATION BLOCKADE; ALLOGRAFT TOLERANCE C1 Harvard Univ, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Sch Med, Boston, MA 02129 USA. NR 68 TC 284 Z9 294 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 2001 VL 14 IS 4 BP 417 EP 424 DI 10.1016/S1074-7613(01)00122-4 PG 8 WC Immunology SC Immunology GA 424TB UT WOS:000168246700009 PM 11336687 ER PT J AU Barrington, R Zhang, M Fischer, M Carroll, MC AF Barrington, R Zhang, M Fischer, M Carroll, MC TI The role of complement in inflammation and adaptive immunity SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ACUTE SEPTIC PERITONITIS; T-DEPENDENT ANTIGEN; B-CELL RESPONSE; ANTIBODY-RESPONSE; LYMPHOCYTES-B; REPERFUSION INJURY; GERMINAL-CENTERS; GUINEA-PIGS; RECEPTOR; CD19 AB Major advances in our understanding of the immunobiology of complement were made within the past 5 years primarily due to the development of gene-targeting technology. New strains of mice bearing specific deficiencies in serum complement proteins or their receptors were developed using this approach. Characterization of these mice has provided new and exciting insights into the biology of the complement system. In this review, we discuss recent results on two important aspects of the complement system, i) host protection and inflammation, and ii) regulation of B lymphocytes of adaptive immunity. While these two roles appear distinct, they are linked. We discuss how natural antibody and classical pathway complement work together in host protection against bacterial infection on the one hand bur, on the other, they co-operate to induce inflammation as observed in reperfusion injury. Significantly, the lymphocytes that produce natural antibody, the B-1 lymphocytes, are regulated in part by the complement system. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Univ Vienna, Inst Immunol, Vienna, Austria. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 43 TC 123 Z9 130 U1 1 U2 12 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2001 VL 180 BP 5 EP 15 DI 10.1034/j.1600-065X.2001.1800101.x PG 11 WC Immunology SC Immunology GA 438XF UT WOS:000169079000001 PM 11414363 ER PT J AU Tu, ZC Dewhirst, FE Blaser, MJ AF Tu, ZC Dewhirst, FE Blaser, MJ TI Evidence that the Campylobacter fetus sap locus is an ancient genomic constituent with origins before mammals and reptiles diverged SO INFECTION AND IMMUNITY LA English DT Article ID SURFACE ARRAY PROTEINS; NESTED DNA INVERSION; LAYER PROTEINS; VIBRIO-FETUS; PATHOGENESIS; RECA; LIPOPOLYSACCHARIDE; INFECTIONS; SEQUENCES; RECOMBINATION AB Campylobacter fetus bacteria, isolated from both mammals and reptiles, may be either subsp. fetus or subsp. venerealis and either serotype A or serotype B. Surface layer proteins, expressed and secreted by genes in the sap locus, play an important role in C, fetus virulence. To assess whether the sap locus represents a pathogenicity island and to gain further insights into C. fetus evolution, we examined several C. fetus genes in 18 isolates. All of the isolates had 5 to 9 sapA or sapB homologs. One strain (85-387) possessed both sapA and sapB homologs, suggesting a recombinational event in the sap locus between sapA and sapB strains. When we amplified and analyzed nucleotide sequences from portions of housekeeping gene recA (501 bp) and sapD (450 bp), a part of the 6-kb sap invertible element, the phylogenies of the genes were highly parallel. Among the 15 isolates from mammals, serotype A and serotype B strains generally had consistent positions. The fact that the serotype A C. fetus subsp. fetus and subsp. venerealis strains were on the same branch suggests that their differentiation occurred after the type A-type B split. Isolates from mammals and reptiles formed two distinct tight phylogenetic clusters that were well separated. Sequence analysis of 16S rRNA showed that the reptile strains form a distinct phylotype between mammalian C. fetus and Campylobacter hyointestinalis. The phylogenies and sequence results showing that sapD and recA have similar G + C contents and substitution rates suggest that the sap locus is not a pathogenicity island but rather is an ancient constituent of the C. fetus genome, integral to its biology. C1 Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37212 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. Forsyth Inst, Dept Mol Genet, Boston, MA USA. RP Blaser, MJ (reprint author), NYU, Sch Med, Dept Med, 550 1st Ave, New York, NY 10016 USA. FU PHS HHS [R01 A124145] NR 48 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2001 VL 69 IS 4 BP 2237 EP 2244 DI 10.1128/IAI.69.4.2237-2244.2001 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 413MT UT WOS:000167616500032 PM 11254579 ER PT J AU Vorup-Jensen, T Sorensen, ES Jensen, UB Schwaeble, W Kawasaki, T Ma, Y Uemura, K Wakamiya, N Suzuki, Y Jensen, TG Takahashi, K Ezekowitz, RAB Thiel, S Jensenius, JC AF Vorup-Jensen, T Sorensen, ES Jensen, UB Schwaeble, W Kawasaki, T Ma, Y Uemura, K Wakamiya, N Suzuki, Y Jensen, TG Takahashi, K Ezekowitz, RAB Thiel, S Jensenius, JC TI Recombinant expression of human mannan-binding lectin SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE structural and functional comparison recombinant mannan-binding lectins carbohydrate affinity chromatography complement deficiency ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLLAGEN-LIKE DOMAIN; RHEUMATOID-ARTHRITIS; SERINE-PROTEASE; CYSTIC-FIBROSIS; STRUCTURAL GENE; MANNOSE; COMPLEMENT; SERUM; ASSOCIATION AB Mannan-binding lectin (MBL) constitutes an important part of the innate immune defend by effecting the deposition of complement on microbial surfaces. MBL deficiency is among the most common primary immunodeficiencies and is associated with recurrent infections and symptoms of poor immune complex clearance. Plasma-derived MBL has been used in reconstitution therapy but concerns over viral contamination and production capacity point to recombinant MBL (rMBL) as a future source of this protein for clinical use. Natural human MBL is an oligomer of up to 18 identical polypeptide chains. The synthesis of rMBL has been accomplished in several mammalian cell lines, however, the recombinant protein differed structurally from natural MEL. In this, study we compare rMBL produced in myeloma cells, Chinese hamster ovary (CHO) cells, human hepatocytes, and human embryonic kidney (HEK) cells. We report that rMBL structurally and functionally similar to natural MBL can be obtained through synthesis in the human embryonic kidney cells followed by selective carbohydrate affinity chromatography. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Aarhus, Dept Med Microbiol & Immunol, DK-8000 Aarhus C, Denmark. Aarhus Univ, Prot Lab, DK-8000 Aarhus, Denmark. Aarhus Univ, Dept Human Genet, DK-8000 Aarhus C, Denmark. Univ Leicester, Dept Microbiol & Immunol, Leicester LE1 9HN, Leics, England. Kyoto Univ, Grad Sch Pharmaceut Sci, Japan Sci & Technol Corp, Dept Biol Chem,Sakyo Ku, Kyoto 6068501, Japan. Kyoto Univ, Grad Sch Pharmaceut Sci, Japan Sci & Technol Corp, Core Res Evolut Sci & Technol Project,Sakyo Ku, Kyoto 6068501, Japan. Osaka Univ, Osaka Prefectural Inst Publ Hlth, Microbial Dis Res Inst, Suita, Osaka, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. RP Vorup-Jensen, T (reprint author), Univ Aarhus, Dept Med Microbiol & Immunol, Bartholin Bldg,Wilhelm Meyers Alle, DK-8000 Aarhus C, Denmark. RI Suzuki, Yasuhiko/F-6890-2012; OI Vorup-Jensen, Thomas/0000-0002-4140-6563 NR 47 TC 48 Z9 52 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD APR PY 2001 VL 1 IS 4 BP 677 EP 687 DI 10.1016/S1567-5769(00)00052-7 PG 11 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 434NF UT WOS:000168821800007 PM 11357880 ER PT J AU Ronald, AR Nicolle, LE Stamm, E Krieger, J Warren, J Schaeffer, A Naber, KG Hooton, TM Johnson, J Chambers, S Andriole, V AF Ronald, AR Nicolle, LE Stamm, E Krieger, J Warren, J Schaeffer, A Naber, KG Hooton, TM Johnson, J Chambers, S Andriole, V TI Urinary tract infection in adults: research priorities and strategies SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article; Proceedings Paper CT 6th International Symposium on Clinical Evaluation of Drug Efficacy in Urinary Tract Infection held at the 21st International Chemotherapy Congress CY JUL, 1999 CL BIRMINGHAM, ENGLAND DE urinary tract infection; prevention and care; adults; research priorities ID ESCHERICHIA-COLI; ASYMPTOMATIC BACTERIURIA; ANTIMICROBIAL TREATMENT; ACUTE PYELONEPHRITIS; NATURAL-HISTORY; WOMEN; THERAPY; PROSTATITIS; PREVENTION; DIAGNOSIS AB Waning interest in urinary tract infection (UTI) research has limited clinical advances during the past two decades. Although care has improved for some specific UTI syndromes. there is limited evidence for most of the decisions made each day in the management of these infections. Additional clinical research is necessary to improve UTI prevention and care strategies. (C) 2001 Published by Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. C1 Univ Manitoba, St Boniface Gen Hosp, Infect Dis Sect, Winnipeg, MB R2H 2A6, Canada. C4 Hlth Sci Ctr, Dept Med, Winnipeg, MB R3A IR9, Canada. Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Sect Urol I 12 LJR, Seattle, WA 98108 USA. Univ Maryland, Sch Med, Div Infect Dis, Baltimore, MD 21201 USA. Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA. Klinikum St Elisabeth, Urol Klin, D-94315 Straubing, Germany. Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. Christchurch Hosp, Dept Infect Dis, Christchurch, New Zealand. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. RP Ronald, AR (reprint author), Univ Manitoba, St Boniface Gen Hosp, Infect Dis Sect, Winnipeg, MB R2H 2A6, Canada. OI Ronald, Allan/0000-0002-5746-3490 NR 29 TC 52 Z9 55 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD APR PY 2001 VL 17 IS 4 BP 343 EP 348 DI 10.1016/S0924-8579(01)00303-X PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 421DH UT WOS:000168046500020 PM 11295419 ER PT J AU Nielsen, GP Young, RH AF Nielsen, GP Young, RH TI Mesenchymal tumors and tumor-like lesions of the female genital tract: A selective review with emphasis on recently described entities SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Review DE female genital tract; soft tissue tumors; benign mesenchymal neoplasms; malignant mesenchymal neoplasms; tumor-like lesions ID SMOOTH-MUSCLE TUMORS; PRIMITIVE NEUROECTODERMAL TUMOR; MALIGNANT FIBROUS HISTIOCYTOMA; SPINDLE-CELL NODULE; MASSIVE LOCALIZED LYMPHEDEMA; BENIGN NEOPLASM DISTINCT; SOFT-PART SARCOMA; AGGRESSIVE ANGIOMYXOMA; UTERINE CERVIX; GLOMUS TUMOR AB The diverse mesenchymal tumors and tumor-like lesions that occur within the female genital tract include a number of lesions that have only been recently characterized and others about which there is new information. In this group are the aggressive angiomyxoma, angiomyofibroblastoma, and cellular angiofibroma. Criteria for the distinction of these lesions are reviewed, as are the pathologic features of prognostic significance in assessing smooth muscle tumors of the vulva. The diagnostic problems that the epithelioid variant of smooth muscle tumors, both benign and malignant, may pose when they occur in various areas of the genital tract are discussed, particularly with regard to problems encountered in the ovary, a site where the diagnosis often is not considered. Recent information expanding the morphologic spectrum of fibroepithelial polyps of the genital tract is presented, and important non-neoplastic entities, including nodular fasciitis and the postoperative spindle cell nodule, are reviewed. Mesenchymal tumors of the various types seen in the soft tissues may be encountered anywhere in the female genital tract and have been the subject of particular recent interest in the ovary; issues relevant to differential diagnosis are re viewed. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. NR 202 TC 42 Z9 45 U1 1 U2 2 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 APR PY 2001 VL 20 IS 2 BP 105 EP 127 DI 10.1097/00004347-200104000-00002 PG 23 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 414WZ UT WOS:000167690300003 PM 11293156 ER PT J AU Sattler, M Griffin, JD AF Sattler, M Griffin, JD TI Mechanisms of transformation by the BCR/ABL oncogene SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Review DE BCR/ABL; signal transduction; chronic myelogenous leukemia ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; DNA-BINDING ACTIVITY; SIGNAL-TRANSDUCTION PATHWAYS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; GROWTH-FACTOR INDEPENDENCE; HEMATOPOIETIC-CELL LINES; CHRONIC MYELOMONOCYTIC LEUKEMIA AB The Philadelphia chromosome generates a chimeric oncogene in which the BCR and c-ABL genes ate fused. The product of this oncogene, BCR/ABL, has elevated ABL tyrosine kinase activity relocates to the cytoskeleton. and phosphorylates multiple cellular substrates. BCR/ABL transforms hematopoietic cells and exerts a wide variety of biological effects, including reduction in growth factor dependence, enhanced viability, and altered adhesion of chronic myelocytic leukemia (CML) cells. Elevated tyrosine kinase activity of BCR/ABL is critical for activating downstream signal transduction and for all aspects of transformation. This review will describe mechanisms of transformation by the BCR/ABL oncogene and opportunities for clinical intervention with specific signal transduction inhibitors such as STI-571 in CML. (C) 2001 The Japanese Society of Hematology. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Brigham & Womens Hosp, Dept Med, 44 Binney St, Boston, MA 02115 USA. EM james_griffin@dfci.harvard.edu NR 212 TC 40 Z9 43 U1 0 U2 6 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0925-5710 EI 1865-3774 J9 INT J HEMATOL JI Int. J. Hematol. PD APR PY 2001 VL 73 IS 3 BP 278 EP 291 DI 10.1007/BF02981952 PG 14 WC Hematology SC Hematology GA 430YZ UT WOS:000168604200002 PM 11345193 ER PT J AU Cubilla, AL Reuter, V Velazquez, E Piris, A Saito, S Young, RH AF Cubilla, AL Reuter, V Velazquez, E Piris, A Saito, S Young, RH TI Histologic classification of penile carcinoma and its relation to outcome in 61 patients with primary resection SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE penis; squamous cell carcinoma; histologic subtypes; prognosis ID SQUAMOUS-CELL-CARCINOMA; HUMAN PAPILLOMAVIRUS; VARIANTS; SURVIVAL; CANCER; TUMORS; BRAZIL; GRADE AB A retrospective review of the clinical and pathologic features of 61 cases of penile squamous cell carcinoma (SCC), all treated by primary surgical resection at the Memorial Sloan Kettering Cancer Center during the period 1949-1992, was undertaken. Inguinal lymph node dissection material was evaluated in 40 cases. All carcinomas were of squamous cell type and were classified as follows: usual type, 36 cases (59%); papillary, not otherwise specified (NOS), 9 cases (15%), basaloid, 6 cases (10%): warty (condylomatous), 6 cases (10%); verrucous, 2 cases (3%), and sarcomatoid, 2 cases (3%). A high rate of nodal metastasis and poor survival were found for the basaloid and sarcomatoid neoplasms (5 of 7 patients with metastasis, 71%, and 5 of 8 dead of disease, 63%). Only 1 patient with a verruciform tumor (defined as a tumor of nonspecific papillary, warty, or verrucous type) had inguinal node metastasis and none died from penile cancer. An intermediate rate of metastasis and mortality (14 of 26, 54%, and 13 of 36, 36%, respectively) was found for typical SCC. Penile carcinomas are morphologically heterogeneous, and there is a correlation of histologic type and biologic behavior. This mandates accurate histologic subtyping by the pathologist. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Inst Patol & Invest, Asuncion, Paraguay. NYU, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Reuter, V (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. NR 37 TC 54 Z9 55 U1 0 U2 2 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD APR PY 2001 VL 9 IS 2 BP 111 EP 120 DI 10.1177/106689690100900204 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 450XK UT WOS:000169770000004 PM 11484498 ER PT J AU Maluf, H Koerner, F AF Maluf, H Koerner, F TI Lobular carcinoma in situ and infiltrating ductal carcinoma: Frequent presence of DCIS as a precursor lesion SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lobular carcinoma in situ; ductal carcinoma in situ; infiltrating ductal carcinoma; E-cadherin; tubular carcinoma ID E-CADHERIN EXPRESSION; IN-SITU; BREAST-CANCER; INVASIVE CANCER; PROSPECTIVE NATIONWIDE; CHROMOSOME 11Q13; FEMALE BREAST; FOLLOW-UP; INSITU; HETEROZYGOSITY AB Infiltrating ductal carcinoma (IDC) occurs frequently in patients with lobular carcinoma in-situ (LCIS). LCIS is not thought to be the direct precursor of the invasive component. The authors analyzed 15 cases of coexisting LCIS and IDC and found ductal carcinoma in situ (DCIS) in 12. The DCIS and IDC were of similar grade and located in the same area. Selected cases stained with E-cadherin demonstrated a different immunophenotype for the lobular and ductal lesions. These results support the notion that DCIS is the direct precursor of IDC occurring in patients with LCIS. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Maluf, H (reprint author), Washington Univ, Sch Med, Dept Pathol, Div Surg Pathol, 660 S Euclid Ave,Box 8118, St Louis, MO 63110 USA. NR 30 TC 17 Z9 17 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD APR PY 2001 VL 9 IS 2 BP 127 EP 131 DI 10.1177/106689690100900206 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 450XK UT WOS:000169770000006 PM 11484500 ER PT J AU Werth, VP AF Werth, VP TI Dermatology vignette SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article C1 Univ Penn, Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Univ Penn, Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA 19104 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD APR PY 2001 VL 7 IS 2 BP 123 EP 123 DI 10.1097/00124743-200104000-00015 PG 1 WC Rheumatology SC Rheumatology GA 428HE UT WOS:000168455200015 PM 17039110 ER PT J AU Faraone, SV Biederman, J Monuteaux, MC AF Faraone, SV Biederman, J Monuteaux, MC TI Attention deficit hyperactivity disorder with bipolar disorder in girls: further evidence for a familial subtype? SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE ADHD; bipolar disorder; genetics; comorbidity; nosology ID ONSET MANIA; ADOLESCENTS; CHILDHOOD; COMORBIDITY; CHILDREN AB Background: To clarify, the nosologic status of girls with attention deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). Methods: Using blind raters and structured psychiatric interviews, we examined 140 girls with ADHD, 122 non-ADHD comparisons and their 786 first degree relatives. Analyses tested specific hypotheses about the familial relationship between ADHD and bipolar disorder in girls. Results: After stratifying our ADHD sample into those with and without BPD, we found that: (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls, (?) the two subgroups did not significantly differ in their relatives' risk for ADHD; (3) an elevated risk for bipolar disorder was observed among relatives when the proband child had BPD but not ADHD alone; (4) weak evidence of cosegregation between ADHD and BPD, and (5) no evidence of a trend for random mating between ADHD parents and those with mania. Limitations: Limitations of this study include the lack of direct interviewing of probands and the limited number of ADHD/BPD probands available. Conclusions: These Findings extend to girls what was previously documented in boys and suggest that comorbid ADI-ID with BPD in girls is familially distinct from other forms of ADHD and may be related to what others have termed childhood onset BPD. Future work could determine: if this subgroup has a characteristic course, outcome and response to treatment. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat,Harvard Inst Psychiat Epidemiol & G, Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA 02115 USA. Massachusetts Hlth Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, ACC 725,Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 29 TC 75 Z9 78 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2001 VL 64 IS 1 BP 19 EP 26 DI 10.1016/S0165-0327(00)00213-5 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 426KF UT WOS:000168347800002 PM 11292516 ER PT J AU Miotto, D Christodoulopoulos, P Olivenstein, R Taha, R Cameron, L Tsicopoulos, A Tonnel, AB Fahy, O Lafitte, JJ Luster, AD Wallaert, B Mapp, CE Hamid, Q AF Miotto, D Christodoulopoulos, P Olivenstein, R Taha, R Cameron, L Tsicopoulos, A Tonnel, AB Fahy, O Lafitte, JJ Luster, AD Wallaert, B Mapp, CE Hamid, Q TI Expression of IFN-gamma-inducible protein; monocyte chemotactic proteins 1, 3, and 4; and eotaxin in T(H)1-and T(H)2-mediated lung diseases SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE chemokines; eotaxin; monocyte chemotactic proteins.; interferon gamma inducible protein; asthma; sarcoidosis; tuberculosis ID PULMONARY SARCOIDOSIS; MESSENGER-RNA; BRONCHOALVEOLAR LAVAGE; CHEMOKINE RECEPTORS; BRONCHIAL BIOPSIES; GENE-EXPRESSION; T-LYMPHOCYTES; CELLS; CHEMOATTRACTANT; INFLAMMATION AB Background: Chemokines are involved in the influx of leukocytes into the airways in inflammatory lung diseases. The differential cell recruitment characteristic of T(H)1 versus T(H)2 immune responses may be associated with differential chemokine expression, Objective: We investigated the expression of chemokines; monocyte chemotactic proteins (MCPs) 1, 3, and 4; eotaxin; and IFN-gamma -inducible protein 10 (IP-10) in both T(H)1- and T(H)2-mediated lung diseases. Methods: By using immunocytochemistry and in situ hybridization, we examined the protein and mRNA expression, respectively. in bronchoalveolar lavage and biopsy samples in subjects with asthma, tuberculosis, sarcoidosis, and chronic bronchitis. Results: Increased immunoreactivity and mRNA expression of IP-10 and of the MCPs was found in the bronchoalveolar lavage fluid and biopsy specimens of subjects with asthma and tuberculosis compared with that of control subjects (P < .005), IP-10, however. was particularly increased in subjects with sarcoidosis (P < .001), Eotaxin, on the other hand, was increased only in patients with asthma when compared with control subjects (P < .005), Conclusion: This study demonstrates that MCP-1, MCP-3, and MCP-4 expression is not specifically associated with lung diseases characterized by a particular cytokine profile, In contrast, IP-10 is mostly expressed in T(H)1-mediated diseases, and eotaxin expression seems to be specifically associated with lung diseases of a T(H)2 cytokine profile. C1 McGill Univ, Meakins Christie Labs, Montreal, PQ H2X 2P2, Canada. Univ Padua, I-35100 Padua, Italy. McGill Univ, Montreal Chest Inst, Montreal, PQ H2X 2P2, Canada. CHR, Calmette Hosp, Inst Pasteur, INSERM,U416, Lille, France. Univ Lille, Lille, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Hamid, Q (reprint author), McGill Univ, Meakins Christie Labs, 3626 St Urbain St, Montreal, PQ H2X 2P2, Canada. NR 43 TC 108 Z9 111 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2001 VL 107 IS 4 BP 664 EP 670 DI 10.1067/mai.2001.113524 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 423RG UT WOS:000168190100019 PM 11295656 ER PT J AU Graybill, JR Bocanegra, R AF Graybill, JR Bocanegra, R TI Treatment alternatives for Mycobacterium kansasii SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NONTUBERCULOUS MYCOBACTERIA; CLARITHROMYCIN; AZITHROMYCIN; SUSCEPTIBILITY; SPARFLOXACIN AB Mycobacterium kansasii was administered intravenously to congenitally athymic (nude) mice. Beginning 1 week later, rifapentine, azithromycin, ethambutol or combined therapy was initiated orally. All three drugs were highly active individually. Although there was no evidence of antagonism, combined therapy was not more effective than either component used alone. C1 Vet Adm Hosp, Infect Dis Serv, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Graybill, JR (reprint author), Vet Adm Hosp, Infect Dis Serv, Box 111F,7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD APR PY 2001 VL 47 IS 4 BP 417 EP 420 DI 10.1093/jac/47.4.417 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 423MB UT WOS:000168179100007 PM 11266413 ER PT J AU Wexler, HM Molitoris, E Molitoris, D Finegold, SM AF Wexler, HM Molitoris, E Molitoris, D Finegold, SM TI In vitro activity of telithromycin (HMR 3647) against 502 strains of anaerobic bacteria SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID HMR-3004 RU-64004; ANTIMICROBIAL AGENTS; HMR-3647 RU-66647; PATHOGENS; GRACILIS; NOV AB In a previous study, we compared HMR 3004 with azithromycin, clarithromycin, erythromycin and roxithromycin against 502 anaerobic bacteria using NCCLS-approved procedures, This report extends this study by reporting the activity of telithromycin (HMR 3647) against these strains, Telithromycin inhibited 10% of Bacteroides fragilis, 50% of other B. fragilis group organisms and 93% of other Bacteroides spp, Telithromycin inhibited all Porphyromonas spp, and 98% of Prevotella spp. Activity against Bilophila wadsworthia (85-96%) was excellent, Telithromycin was not active against the Fusobacterium mortiferum/varium group, Telithromycin inhibited 100% of Clostridium perfringens, 46-56% of Clostridium difficile and Clostridium ramosum and approximately 90% of non-spore-forming Gram-positive bacilli. C1 VA Greater Los Angeles Healthcare Syst, Med Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 90024 USA. RP Wexler, HM (reprint author), Vet Adm Wadsworth Med Ctr, Microbial Dis Res Lab, Bldg 304,Room E3-224,691-151J, Los Angeles, CA 90073 USA. NR 10 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD APR PY 2001 VL 47 IS 4 BP 467 EP 469 DI 10.1093/jac/47.4.467 PG 3 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 423MB UT WOS:000168179100017 PM 11266423 ER PT J AU Fournier, B Truong-Bolduc, QC Zhang, XM Hooper, DC AF Fournier, B Truong-Bolduc, QC Zhang, XM Hooper, DC TI A mutation in the 5 ' untranslated region increases stability of norA mRNA, encoding a multidrug resistance transporter of Staphylococcus aureus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MESSENGER-RNA DEGRADATION; ESCHERICHIA-COLI; BACILLUS-SUBTILIS; FLUOROQUINOLONE RESISTANCE; REITERATIVE TRANSCRIPTION; EXPRESSION; GENE; BACTERIA; STRAINS; SYSTEMS AB NorA, a multidrug efflux pump in Staphylococcus aureus, protects the cell from multiple drugs, including quinolones, The flqB mutation (T-->G) in the 5' untranslated region upstream of norA causes norA overexpression of 4.9-fold in cis, as measured in norA::blaZ fusions. The transcriptional initiation site of norA mas unchanged in mutant and wild-type strains, but the half-life of norA mRNA was increased 4.8-fold in the flqB mutant compared to the wild-type strain. Computer generated folding of the first 68 nucleotides of the norA transcript predicts an additional stem-loop and changes in a putative RNase III cleavage site in the flqB mutant. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [AI23988, R01 AI023988, R37 AI023988]; NIDDK NIH HHS [P30 DK-43351, P30 DK043351] NR 29 TC 46 Z9 47 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2001 VL 183 IS 7 BP 2367 EP 2371 DI 10.1128/JB.183.7.2367-2371.2001 PG 5 WC Microbiology SC Microbiology GA 411RH UT WOS:000167512700028 PM 11244079 ER PT J AU McGibbon, CA Krebs, DE Puniello, MS AF McGibbon, CA Krebs, DE Puniello, MS TI Mechanical energy analysis identifies compensatory strategies in disabled elders' gait SO JOURNAL OF BIOMECHANICS LA English DT Article DE gait analysis; power flow; mechanical energy transfer; compensation; aging; disability ID SWING-THROUGH GAIT; EXPENDITURE PROBLEM; FRACTIONS APPROACH; STANCE PHASE; OLDER ADULTS; MUSCULAR EFFICIENCY; HUMAN LOCOMOTION; ELBOW CRUTCHES; LINK SYSTEM; JOINT POWER AB Current concepts in disablement emphasize the importance of identifying mobility impairments in aging humans to enable timely intervention and, ultimately, prevent disability. Because mobility impairments are likely to result in compensatory movement strategies, recognizing and understanding those strategies may be critical in designing effective interventions for preventing disability. We sought to determine if mechanical energy methods are useful for identifying and understanding lower extremity compensatory movement strategies due to disabilities. Aleshinski's method was used to compute mechanical energy expenditure (MEE) and mechanical energy compensation (MEC) for the sagittal plane stance leg and low-back joints of healthy elders (HE) and disabled elders (DE) during preferred speed and paced (120 steps min(-1)) gait. DE subjects expended less ankle energy in late-stance and more low-back energy in mid-stance than did the HE subjects. When controlling for walking speed, the difference in ankle MEE disappeared, but mid-stance hip MEE was significantly higher for the DE subjects. Despite increased hip and low-back MEE, the DE subjects compensated hip and low-back muscles greater then HE subjects by increasing energy transferred into the pelvis, particularly when walking faster than their self-selected speed. Increased energy transfers into the pelvis during mid-stance may be a strategy used to assist in advancing and controlling the contralateral limb's swing phase. Increased trunk energy, however, may compromise dynamic stability and increase the risk of falling. We conclude that mechanical energy methods are useful for identifying and understanding compensatory movement strategies in elders with disabilities. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed, Boston, MA USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, 40 Parkman St, Boston, MA 02114 USA. FU NIA NIH HHS [P50-AG11669, R01-AG12561] NR 49 TC 39 Z9 40 U1 4 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD APR PY 2001 VL 34 IS 4 BP 481 EP 490 DI 10.1016/S0021-9290(00)00220-7 PG 10 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 421XK UT WOS:000168088700009 PM 11266671 ER PT J AU Allemann, M Mizuno, S Eid, K Yates, KE Zaleske, D Glowacki, J AF Allemann, M Mizuno, S Eid, K Yates, KE Zaleske, D Glowacki, J TI Effects of hyaluronan on engineered articular cartilage extracellular matrix gene expression in 3-dimensional collagen scaffolds SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE tissue engineering; 3-dimensional hyaluronan/collagen scaffolds; in vitro engineered articular cartilage; chondrogenesis; cartilage-specific gene expression ID HUMAN DERMAL FIBROBLASTS; PROTEOGLYCAN SYNTHESIS; DEMINERALIZED BONE; ACID; CHONDROCYTES; CULTURE; CHONDROINDUCTION; CHONDROGENESIS; ATTACHMENT; COMPOSITE AB Hyaluronan (HA) is a component of cartilage matrix with known effects on chondrocytes. We tested the effects of adding HA to 3-dimensional (3-D) collagen sponges on chondrocyte function in vitro. Bovine articular chondrocytes isolated by collagenase digestion were injected into either collagen or HA/collagen scaffolds comprising different amounts of HA (2, 5, 10, and 14% w/w). Expression of aggrecan and type II collagen genes was measured by gene-specific quantitative competitive reverse tanscriptase-polymerase chain reactions, and the extracellular matrix was estimated by histomorphometrical analyses. After 7-day culture, the chondrocytes in 2% (w/w) HA sponges expressed fourfold more mRNA transcripts for type II collagen (p = 0.002) and twofold more mRNA transcripts for aggrecan (p = 0.022) than in control collagen sponges. Furthermore, there was 45% more extracellular matrix in 2% (w/w) HA sponges and 43% less matrix in the 10% (w/w) HA sponges compared with plain collagen sponges (p > 0.05). In sum, a small amount of HA in 3-D collagen scaffolds enhanced chondrogenesis, but a greater amount was inhibitory. This 3-D system represents a novel tool to identify mechanisms by which extracellular matrix molecules influence chondrocyte function. Further, these results show the potential for modifying scaffolds to improve production of engineered cartilage for in vivo applications. (C) 2000 John Wiley & Sons, Inc. C1 Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02115 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. NR 24 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD APR PY 2001 VL 55 IS 1 BP 13 EP 19 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 398JM UT WOS:000166753400002 ER PT J AU Gao, P Scheibel, S D'Amour, P John, MR Rao, SD Schmidt-Gayk, H Cantor, TL AF Gao, P Scheibel, S D'Amour, P John, MR Rao, SD Schmidt-Gayk, H Cantor, TL TI Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1-84: Implications for improvement of accurate assessment of parathyroid function SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE parathyroid hormone; immunoassay; hyperparathyroidism; uremia; parathyroid hormone fragment ID RENAL-FAILURE; 2-SITE ASSAY; INTACT; PTH; OSTEODYSTROPHY; HYPERCALCEMIA; RECEPTOR; CALCIUM; PLASMA; UREMIA AB We developed a novel immunoradiometric assay (IRMA; whole parathyroid hormone [PTH] IRMA) for PTH, which specifically measures biologically active whole PTH(1-84). The assay is based on a solid phase coated with anti-PTH(39-84) antibody, a tracer of I-125-labeled antibody with a unique specificity to the first N-terminal amino acid of PTH(1-84), and calibrators of diluted synthetic PTH(1-84). In contrast to the Nichols intact PTH IRMA, this new assay does not detect PTH(7-84) fragments and only detects one immunoreactive peak in chromatographically fractionated patient samples. The assay was shown to have an analytical sensitivity of 1.0 pg/ml with a linear measurement range up to 2300 pg/ml. With this assay, we further identified that the previously described non-(1-84)PTH fragments are aminoterminally truncated with similar hydrophobicity as PTH(7-84), and these PTH fragments are present not only in patients with secondary hyperparathyroidism (2 degrees -HPT) of uremia, but also in patients with primary hyperparathyroidism (1-HPT) and normal persons. The plasma normal range of the whole PTH(1-84) was 7-36 pg/ml (mean +/- SD: 22.7 a 7.2 pg/ml, n = 135), whereas over 93.9% (155/165) of patients with 1 degrees -HPT had whole PTH(1-84) values above the normal cut-off. The percentage of biologically active whole PTH(1-84) (pB%) in the pool of total immunoreactive "intact" PTH is higher in the normal population (median: 67.3%; SD: 15.8%; n = 56) than in uremic patients (median:53.8%; SD: 15.5%; n = 318; p < 0.001), although the whole PTH(1-84) values from uremic patients displayed a more significant heterogeneous distribution when compared with that of 1-HPT patients and normals. Moreover, the pB % displayed a nearly Gaussian distribution pattern from 20% to over 90% in patients with either 1 degrees -HPT or uremia. The specificity of this newly developed whole PTH(1-84) IRMA is the assurance, for the first time, of being able to measure only the biologically active whole PTH(1-84) without cross-reaction to the high concentrations of the aminoterminally truncated PTH fragments found in both normal subjects and patients. Because of the significant variations of pB % in patients, it is necessary to use the whole PTH assay to determine biologically active PTH levels clinically and, thus, to avoid overestimating the concentration of the true biologically active hormone. This new assay could provide a more meaningful standardization of future PTH measurements with improved accuracy in the clinical assessment of parathyroid function. C1 Scantibodies Lab Inc, Dept R&D & Diagnost, Santee, CA 92071 USA. Univ Montreal, Ctr Rech, Montreal, PQ, Canada. Univ Montreal, CHUM, Montreal, PQ, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Henry Ford Hosp, Detroit, MI 48202 USA. Dept Endocrinol & Oncol, Lab Grp, Heidelberg, Germany. RP Gao, P (reprint author), Scantibodies Lab Inc, Dept R&D & Diagnost, 936 Abraham Way, Santee, CA 92071 USA. NR 29 TC 236 Z9 244 U1 1 U2 1 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 APR PY 2001 VL 16 IS 4 BP 605 EP 614 DI 10.1359/jbmr.2001.16.4.605 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 413JV UT WOS:000167610000002 PM 11315988 ER PT J AU Sweeney, MO Ellison, KE Shea, JB Newell, JB AF Sweeney, MO Ellison, KE Shea, JB Newell, JB TI Provoked and spontaneous high-frequency, low-amplitude, respriophasic noise transients in patients with implantable cardioverter defibrillators SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Cardiology CY MAR 07-10, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Coll Cardiol DE defibrillation; pacemaker; arrhythmia; implantable cardioverter defibrillator; oversensing ID VENTRICULAR-FIBRILLATION; DEMAND PACEMAKERS; INHIBITION; SYSTEM AB Introduction: Ventricular oversensing (OS) of respirophasic noise transients may cause spurious detections and therapies and pacing inhibition among patients with implantable cardioverter defibrillators (ICDs), The incidence of OS and its relationship to clinical variables and ICD system design are unknown, Methods and Results: Three hundred twenty-nine patients performed provocative respiratory maneuvers at rest during intrinsic rhythm and continuous ventricular pacing, OS resulting in spurious ventricular detections was provoked in 3 (0.9%) of 329 patients during intrinsic rhythm and 34 (10.3%) of 329 during pacing. Noise transients not recognized and marked as sensed events, but visually evident on the local endocardial ventricular electrogram, were provoked in an additional 23 (7.0%) of 329 patients. Multivariate logistic regression identified history of spontaneous OS (P < 0.0005, odds ratio 9.7, 95% confidence interval [CI] 1.9 to 50.0). automatic gain control device (P < 0.0005, odds ratio 5.3, 95% CI 2.6 to 10.8) or integrated bipolar lead (P = 0.05, odds ratio 2.6, 95% CI 1.0 to 7.25), and male gender (P = 0.008, odds ratio 3.7, 95% CI 1.2 to 11.1) as predictive of provocable OS. Spontaneous OS resulting in spurious ventricular detections and therapies occurred in 12 (3.6%) patients during follow-up. Eleven of 12 spontaneous episodes occurred in male patients during ventricular pacing; 11 of 12 patients had automatic gain control devices and integrated bipolar leads, Conclusion: OS is commonly provoked in ICD patients during ventricular pacing and may occur spontaneously, causing spurious tachyarrhythmia therapies and pacing inhibition, Differences in the incidence of spontaneous and provoked OS between ICD systems can be explained on the basis of unique features of automatic sensing systems and sensing lead design. C1 Brigham & Womens Hosp, Cardiac Arrhythmia Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sweeney, MO (reprint author), Brigham & Womens Hosp, Cardiac Arrhythmia Serv, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 23 Z9 23 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD APR PY 2001 VL 12 IS 4 BP 402 EP 410 DI 10.1046/j.1540-8167.2001.00402.x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 423AY UT WOS:000168154300003 PM 11332558 ER PT J AU Sheng, M AF Sheng, M TI The postsynaptic NMDA-receptor-PSD-95 signaling complex in excitatory synapses of the brain SO JOURNAL OF CELL SCIENCE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. MGH, Boston, MA 02114 USA. RP Sheng, M (reprint author), MGH, Wellman 423,50 Blossom St, Boston, MA 02114 USA. NR 0 TC 46 Z9 54 U1 0 U2 2 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 APR PY 2001 VL 114 IS 7 BP 1251 EP 1251 PG 1 WC Cell Biology SC Cell Biology GA 423YK UT WOS:000168205200002 PM 11256991 ER PT J AU Criss, AK Ahlgren, DM Jou, TS McCormick, BA Casanova, JE AF Criss, AK Ahlgren, DM Jou, TS McCormick, BA Casanova, JE TI The GTPase Rac1 selectively regulates Salmonella invasion at the apical plasma membrane of polarized epithelial cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE Salmonella typhimurium; actin; epithelial cell; Rac1; Cdc42 ID NUCLEOTIDE EXCHANGE FACTOR; ACTIN STRESS FIBERS; NUCLEAR RESPONSES; RHO-GTPASES; BACTERIAL INVASION; SECRETED PROTEIN; GENE-EXPRESSION; MAMMALIAN-CELLS; HOST-CELL; TYPHIMURIUM AB The bacterial pathogen Salmonella typhimurium colonizes its animal hosts by inducing its internalization into intestinal epithelial cells, This process requires reorganization of the actin cytoskeleton of the apical plasma membrane into elaborate membrane ruffles that engulf the bacteria, Members of the Rho family of small GTPases are critical regulators of actin structure, and in nonpolarized cells, the GTPase Cdc42 has been shown to modulate Salmonella entry. Because the actin architecture of epithelial cells is organized differently from that of nonpolarized cells, we examined the role of two Rho family GTPases, Cdc42 and Rad, in invasion of polarized monolayers of MDCK cells by S. typhimurium. Surprisingly., we found that endogenous Rad, but not Cdc42, was activated during bacterial entry at the apical pole, and that this activation required the bacterial effector protein SopE, Furthermore, expression of dominant inhibitory Rac1 but not Cdc42 significantly inhibited apical internalization of Salmonella, indicating that Rad activation is integral to the bacterial entry process. In contrast, during basolateral internalization, both Cdc42 and Rad were activated; however, neither GTPase was required for entry, These findings, which differ significantly from previous observations in nonpolarized cells, indicate that the host cell signaling pathways activated by bacterial pathogens may vary with cell type, and in epithelial tissues may further differ between plasma membrane domains. C1 Univ Virginia, Dept Cell Biol, Charlottesville, VA 22908 USA. Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. RP Casanova, JE (reprint author), Univ Virginia, Dept Cell Biol, Charlottesville, VA 22908 USA. OI JOU, TZUU-SHUH/0000-0003-4341-5137 FU NIDDK NIH HHS [DK50989, DK52531] NR 53 TC 70 Z9 72 U1 1 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 APR PY 2001 VL 114 IS 7 BP 1331 EP 1341 PG 11 WC Cell Biology SC Cell Biology GA 423YK UT WOS:000168205200010 PM 11256999 ER PT J AU Gazitt, Y Reddy, SV Alcantara, O Yang, J Boldt, DH AF Gazitt, Y Reddy, SV Alcantara, O Yang, J Boldt, DH TI A new molecular role for iron in regulation of cell cycling and differentiation of HL-60 human leukemia cells: Iron is required for transcription of p21(WAF1/CIP1) in cells induced by phorbol myristate acetate SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; FAS-MEDIATED APOPTOSIS; GENE-EXPRESSION; P53-INDEPENDENT INDUCTION; MONOCYTIC DIFFERENTIATION; RIBONUCLEOTIDE REDUCTASE; PKC-BETA; T-CELLS; P21; ACTIVATION AB To investigate the role of iron in hematopoiesis, we studied effects of iron deprivation on PMA-induced monocyte/macrophage differentiation in HL-60 cells. Iron deprivation induced by desferrioxamine (DF) blocked PMA-induced differentiation and induced S-phase arrest and apoptosis in up to 60% of cells. Apoptosis was not related to a decrease of bcl-2 or to c-myc overexpression. In the presence of DF, PMA-induced upregulation of the cyclin dependent kinase inhibitor (CDKI), p21(WAF1/CIP1), was blocked and its expression could be restored in the presence of DF by supplementation with ferric citrate. Furthermore, ferrioxamine (iron saturated DF) did not block induction of p21(WAF1/CIP1) indicating that the changes were not due to a nonspecific toxic effect of DF. Similarly, hydroxyurea, an inhibitor of ribonucleotide reductase, did not block p21 expression. p21(WAF1/CIP1) antisense oligonucleotides caused cell cycle alterations similar to DF and p21 overexpression overcame effects of iron deprivation on both cell cycling and differentiation. Therefore, p21 is a key target for the effects of iron deprivation on HL-60 cell cycling and differentiation. Nuclear run-on transcription assays and p21 mRNA half-life studies indicated that iron was required to support transcriptional activation of p21(WAF1/CIP1) after a PMA stimulus. By contrast, iron deprivation did not inhibit expression of a second CDKI, p27(KIP1), These data demonstrate a new role for iron during monocyte/ macrophage differentiation. A key role of iron is to allow induction of p21(WAF1/ CIP1) in response to a differentiation stimulus subsequently blocking cells at the G(1)/S cell cycle interface and preventing premature apoptosis. This effect of iron is independent of its requirement in supporting the activity of the enzyme, ribonucleotide reductase. Because of the central role of p21(WAF1/CIP1) as regulator of the G(1)/S cell cycle checkpoint this requirement for iron to support p21 expression represents an important mechanism by which iron may modulate hematopoietic cell growth and differentiation. Published 2001 Wiley-Liss, Inc.(dagger). C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Gazitt, Y (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, 7703 Floyd Curl Dr,Mail Code 7880, San Antonio, TX 78229 USA. FU NCI NIH HHS [CA 40035]; NIDDK NIH HHS [DK 5042225] NR 59 TC 41 Z9 41 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD APR PY 2001 VL 187 IS 1 BP 124 EP 135 DI 10.1002/1097-4652(2001)9999:9999<::AID-JCP1061>3.0.CO;2-E PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 408BE UT WOS:000167306000014 PM 11241357 ER PT J AU Cao, GD Minami, M Pei, W Yan, CH Chen, DX O'Horo, C Graham, SH Chen, J AF Cao, GD Minami, M Pei, W Yan, CH Chen, DX O'Horo, C Graham, SH Chen, J TI Intracellular Bax translocation after transient cerebral ischemia: Implications for a role of the mitochondrial apoptotic signaling pathway in ischemic neuronal death SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral ischemia; apoptosis; Bax; caspases; mitochondria ID PERMEABILITY TRANSITION PORE; PROGRAMMED CELL-DEATH; CYTOCHROME-C RELEASE; DNA FRAGMENTATION; ANTIAPOPTOTIC BCL-2; ARTERY OCCLUSION; GLOBAL-ISCHEMIA; ACTIVATION; INDUCTION; EXPRESSION AB Activation of terminal caspases such as caspase-3 plays an important role in the execution of neuronal cell death after transient cerebral ischemia. Although the precise mechanism by which terminal caspases are activated in ischemic neurons remains elusive, recent studies have postulated that the mitochondrial cell death-signaling pathway may participate in this process. The bcl-2 family member protein Bax is a potent proapoptotic molecule that, on translocation from cytosol to mitochondria, triggers the activation of terminal caspases by increasing mitochondrial membrane permeability and resulting in the release of apoptosis-promoting factors, including cytochrome c. In the present study, the role of intracellular Bax translocation in ischemic brain injury was investigated in a rat model of transient focal ischemia (30 minutes) and reperfusion (1 to 72 hours). Immunochemical studies revealed that transient ischemia induced a rapid translocation of Bax from cytosol to mitochondria in caudate neurons, with a temporal profile and regional distribution coinciding with the mitochondrial release of cytochrome c and caspase-9. Further, in postischemic caudate putamen in vivo and in isolated brain mitochondria in vitro, the authors found enhanced heterodimerization between Bax and the mitochondrial membrane permeabilization-related proteins adenine nucleotide translocator (ANT) and voltage-dependent anion channel. The ANT inhibitor bongkrekic acid prevented Bax and ANT interactions and inhibited Bax-triggered caspase-9 release from isolated brain mitochondria in vitro. Bongkrekic acid also offered significant neuroprotection against ischemia-induced caspase-3 and caspase-9 activation and cell death in the brain. These results strongly suggest that the Bax-mediated mitochondrial apoptotic signaling pathway may play an important role in ischemic neuronal injury. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507 Biomed Sci Tower, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [NS 35965, NS 36736, NS 38650] NR 59 TC 163 Z9 185 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2001 VL 21 IS 4 BP 321 EP 333 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 421PT UT WOS:000168073300001 PM 11323518 ER PT J AU Sesmilo, G Biller, BMK Llevadot, J Hayden, D Hanson, G Rifai, N Klibanski, A AF Sesmilo, G Biller, BMK Llevadot, J Hayden, D Hanson, G Rifai, N Klibanski, A TI Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: A randomized controlled trial SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TOTAL HOMOCYSTEINE LEVELS; VASCULAR ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR RISK-FACTORS; HYPOPITUITARY ADULTS; INSULIN SENSITIVITY; ACUTE HYPERINSULINEMIA; PLASMA HOMOCYST(E)INE; BODY-COMPOSITION; HEART-DISEASE; BONE-DENSITY AB GH deficiency is associated with increased cardiovascular mortality and early manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been found to be associated with increased cardiovascular risk. The effect of GH replacement on homocyst(e)ine has not been investigated to date. We evaluated the effect of GH replacement on fasting homocyst(e)inemia in a group of men with adult-onset GH deficiency in a randomized, single blind, placebo-controlled trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo for 18 months. with dose adjustments made according to serum insulin-like growth factor I(IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and total T(3) levels were determined at baseline and 6 and 18 months. Anthropometry, IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months. Nutritional assessment, body composition, total T,, thyroid hormone binding index, and free T, index were assessed every 6 months. Homocyst(e)ine decreased in the GH-treated group compared with that in the placebo group (net difference, -1.2 +/- 0.6 mu mol/L; confidence interval, -2.4, -0.02 mu mol/L; P = 0.047). Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate (r = -0.41; P = 0.0087). Total T, increased in the GH-treated group us. that in the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confidence interval. 0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 levels did not significantly change between groups. Changes in homocyst(e)ine were negatively correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I, homocyst(e)ine decreased by 0.04 r 0.02 mu mol/L (P = 0.029). In contrast, changes in homocyst(e)ine did not correlate with changes in folate, vitamin B12, total T(3), C-reactive protein, interleukin-6, or insulin levels. This study shows that GH replacement decreases fasting homocyst(e)ine levels compared with placebo. This may be one of the mechanisms involved in the putative modulation of atherosclerosis and cardiovascular risk by GH replacement. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Lab Med & Pathol, Boston, MA 02114 USA. Childrens Hosp, Dept Lab Med & Pathol, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Fruit St,Bulfinch 457B, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [DK-08783] NR 56 TC 36 Z9 39 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 APR PY 2001 VL 86 IS 4 BP 1518 EP 1524 DI 10.1210/jc.86.4.1518 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 424QM UT WOS:000168243000014 PM 11297577 ER PT J AU Oliveira, LMB Seminara, SB Beranova, M Hayes, FJ Valkenburgh, SB Schipani, E Costa, EMF Latronico, AC Crowley, WF Vallejo, M AF Oliveira, LMB Seminara, SB Beranova, M Hayes, FJ Valkenburgh, SB Schipani, E Costa, EMF Latronico, AC Crowley, WF Vallejo, M TI The importance of autosomal genes in Kallmann syndrome: Genotype-phenotype correlations and neuroendocrine characteristics SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; SINGLE-BASE CHANGES; KAL GENE; LUTEINIZING-HORMONE; X-CHROMOSOME; GENOMIC DNA; GC-CLAMP; MUTATIONS; HETEROGENEITY; DELETION AB Kallmann syndrome (KS) consists of congenital, isolated, idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. The gene responsible for the X-linked form of KS, KAL, encodes a protein, anosmin, that plays a key role in the migration of GnRH neurons and olfactory nerves to the hypothalamus. In addition to X-linked pedigrees, autosomal dominant and recessive kindreds with KS have been reported. The relative importance of these autosomal vs. X-linked genes in producing KS, and the frequency of KAL mutations, are currently unknown because these are rare disorders and large series are unusual. We examined 101 individuals with IHH (+/- anosmia) and their families to determine their modes of inheritance, incidence of mutations in the coding sequence of KAL, genotype-phenotype correlations, and [in a subset (n = 38)] their neuroendocrine phenotype. Of the 101 patients, 59 had true KS (IHH + anosmia/hyposmia); whereas, in the remaining 42, no anosmia was evident in the patients or their families. Of the 59 KS patients, 21 were familial, whereas 38 were sporadic cases. Mutations in the coding sequence of KAL were identified in only 3 of 21 familial cases (14%) and 4 of 38 (11%) of the sporadic cases. Of the X-linked cases confirmed by mutational analysis, only 1 of 3 pedigrees appeared X-linked by inspection whereas the other 2 contained only affected brothers. Female members of known KAL mutation families (n = 3) exhibited no reproductive phenotype and were not anosmic, whereas families with anosmic women (n = 3)were not found to carry mutations in KAL. Mutations were uniformly absent in nonanosmic IHH probands (n = 42), as well as in families with both anosmic and nonanosmic members (n = 2). Overall, 4 novel mutations were identified (C172R, R191x, R457x, and delC@L600). With respect to neuroendocrine phenotype, KS men with documented KAL mutations (n = 8) had completely apulsatile LH secretion, whereas those with autosomal modes of inheritance demonstrated a more variable spectrum with evidence of enfeebled (but present) GnRH-induced LH pulses. Our conclusions are: 1) Confirmed mutations in the coding sequence of the KAL gene occur in the minority of KS cases, i.e. only 14% of familial and 11% of sporadic cases; 2) The majority of familial land presumably sporadic) cases of KS are caused by defects in at least two autosomal genes that are currently unknown; 3) Obligate female carriers in families with KAL mutations have no discernible phenotype; 4) KAL mutations are uniformly absent in patients with either normosmic IHH or in families with both anosmic and nonanosmic individuals: and 5) Patients with KAL mutations have apulsatile LH secretion consistent with a complete absence of GnRH migration of GnRH cells into the hypothalamus, whereas evidence of present (but enfeebled) GnRH-induced LH pulses may be present in autosomal KS cases. Taken together, these findings suggest that autosomal genes account for the majority of familial cases of KS, and that unique neuroendocrine phenotypes consistent with some GnRH neuronal migration may exist in these patients. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Sao Paulo, Fac Med, Unidade Endocrinol Desenvolvimento, Sao Paulo, Brazil. RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Reprod Endocrine Sci Ctr, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM crowley.william@mgh.harvard.edu RI Latronico, Ana Claudia/E-1198-2012; OI Latronico Xavier, Ana Claudia/0000-0001-6782-693X FU NICHD NIH HHS [R01 HD015788, U54 HD028138, U54 HD029164] NR 35 TC 132 Z9 138 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2001 VL 86 IS 4 BP 1532 EP 1538 DI 10.1210/jc.86.4.1532 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 424QM UT WOS:000168243000016 PM 11297579 ER PT J AU Beranova, M Oliveira, LMB Bedecarrats, GY Schipani, E Vallejo, M Ammini, AC Quintos, JB Hall, JE Martin, KA Hayes, FJ Pitteloud, N Kaiser, UB Crowley, WF Seminara, SB AF Beranova, M Oliveira, LMB Bedecarrats, GY Schipani, E Vallejo, M Ammini, AC Quintos, JB Hall, JE Martin, KA Hayes, FJ Pitteloud, N Kaiser, UB Crowley, WF Seminara, SB TI Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; GNRH RECEPTOR; GENE; MEN; EXPRESSION; SECRETION; DEFICIENCY; MOLECULES; INDUCTION; OVULATION AB Mutations in the GnRH receptor (GNRHR) have been described as a cause of reproductive failure in a subset of patients with idiopathic hypogonadotropic hypogonadism (IHH). Given the apparent rarity of these mutations, we set out to determine the frequency and distribution of GNRHR mutations in a heterogeneous population of patients with IHH who were well characterized with respect to diagnosis, phenotype, and mode of inheritance and to define their distribution within the receptor protein. One hundred and eight probands with IHH were screened for mutations in the coding sequence of GNRHR. Forty-eight of the 108 patients had a normal sense of smell, whereas the remaining 60 had anosmia or hyposmia (Kallmann syndrome). Exon segments in the GNRHR were screened for mutations using temperature gradient gel electrophoresis, and all mutations were confirmed by direct sequencing. Five unrelated probands (3 men and 2 women), all normosmic, were documented to have changes in the coding sequence of the GNRHR. Two of these probands were from a subgroup of 5 kindreds consistent with a recessive mode of inheritance, establishing a GNRHR mutation frequency of 2 of 5 (40%) in patients with normosmic, autosomal recessive IHH. The remaining 3 probands with GNRHR mutations were from a subgroup of 18 patients without evidence of familial involvement, indicating a prevalence of 3 of 18 (16.7%) in patients with sporadic IHH and a normal sense of smell. Among the five individuals bearing GNRHR mutations, a broad spectrum of phenotypes was noted, including testicular sizes in the male that varied from prepubertal to the normal adult male range. Three probands had compound heterozygous mutations, and two had homozygous mutations. Of the eight DNA sequence changes identified; four were novel: Thr(32)Ile, Cys(200)Tyr, Leu(266)Arg, and Cys(279)Tyr. COS-7 cells transiently transfected with complementary DNAs encoding the human GNRNR containing each of these four novel mutations failed to respond to GnRH agonist stimulation. We conclude that 1) the spectrum of phenotypes in patients with GNRHR mutations is much broader than originally anticipated; 2) the frequency of GNRNR mutations may be more common than previously appreciated in familial cases of normosmic IHH and infrequent in sporadic cases; and 3) functional mutations of the GNRHR are distributed widely throughout the protein. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Harvard Wide Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Endocrine Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi 110029, India. New York Hosp, Cornell Med Ctr, Dept Pediat, Div Pediat Endocrinol, New York, NY 10021 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Harvard Wide Reprod Endocrine Sci Ctr, Bartlett Hall Extens 505, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu RI PITTELOUD, Nelly/K-2709-2014 FU NICHD NIH HHS [P30 HD028138, R01 HD015788, R01-HD-19938, U54 HD028138, U54 HD029164, U54-HD-28138, U54-HD-29164] NR 35 TC 155 Z9 159 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2001 VL 86 IS 4 BP 1580 EP 1588 DI 10.1210/jc.86.4.1580 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 424QM UT WOS:000168243000024 PM 11297587 ER PT J AU Gimm, O Chi, HB Dahia, PLM Perren, A Hinze, R Komminoth, P Dralle, H Reynolds, PR Eng, C AF Gimm, O Chi, HB Dahia, PLM Perren, A Hinze, R Komminoth, P Dralle, H Reynolds, PR Eng, C TI Somatic mutation and germline variants of MINPP1, a phosphatase gene located in proximity to PTEN on 10q23.3, in follicular thyroid carcinomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INOSITOL POLYPHOSPHATE PHOSPHATASE; RILEY-RUVALCABA-SYNDROME; RET PROTOONCOGENE; COWDEN-SYNDROME; HIRSCHSPRUNG-DISEASE; OVER-REPRESENTATION; CODON-918 MUTATION; SEQUENCE VARIANTS; TUMORS; EXPRESSION AB Various genes have been identified to play a role in the pathogenesis of follicular thyroid tumors. Cowden syndrome is the only known familial syndrome with an increased risk of both follicular thyroid adenoma (FA) and carcinoma (FTC). Germline mutations in the tumor suppressor gene PTEN, which encodes a dual-specificity phosphatase, have been found in up to 80% of patients with Cowden syndrome suggesting a role of PTEN in the pathogenesis of follicular thyroid tumors. Although somatic intragenic mutations in PTEN, which maps to 10q23.3, are rarely found in follicular tumors, loss of heterozygosity (LOH) of markers within 10q22-24 occurs in about 25%. Recently, another phosphatase gene, MINPP1, has been localized to 10q23.3. MINPP1 has the ability to remove 3-phosphate from inositol phosphate substrates, a function that overlaps that of PTEN. Because of this overlapping function with PTEN and the physical location of MINPP1 to a region with frequent LOH in follicular thyroid tumors, we considered it to be an excellent candidate gene that could contribute to the pathogenesis of follicular thyroid tumors. We analyzed DNA from tumor and corresponding normal tissue from 23 patients with FA and 15 patients with FTC for LOH and mutations at the MINPP1 locus. LOH was identified in four malignant and three benign tumors. One of these FTCs with LOH was found to harbor a somatic c.122C > T or S41L mutation. We also found two germline sequence variants, c.809A > G (Q270R) and IVS3 + 34T > A. The c.809A > G variant was found in only one patient with FA but not in patients with FTC or normal controls. More interestingly, IVS3 + 34T > A was found in about 15% of FA cases and normal controls but not in patients with FTC. These results suggest a role for MINPP1 in the pathogenesis of at least a subset of malignant follicular thyroid tumors, and MINPP1 might act as a low penetrance predisposition allele for FTC. C1 Univ Cambridge, Human Canc Genet Res Grp, Canc Res Campaign, Cambridge CB2 2QQ, England. Univ Halle Wittenberg, Dept Gen Surg, D-06097 Halle, Germany. Univ Halle Wittenberg, Inst Pathol, D-06097 Halle, Germany. Univ Zurich, Dept Pathol, CH-8091 Zurich, Switzerland. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Rochester, Sch Med, Dept Orthoped, Rochester, NY 14642 USA. Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Human Canc Genet Program, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Eng, C (reprint author), Ohio State Univ, Human Canc Genet Program, Ctr Comprehens Canc, 420 W 12th Ave,Room 690C TMRF, Columbus, OH 43210 USA. EM eng-1@medctr.osu.edu OI Eng, Charis/0000-0002-3693-5145; Perren, Aurel/0000-0002-6819-6092 FU NCI NIH HHS [P30CA16058] NR 32 TC 27 Z9 30 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 APR PY 2001 VL 86 IS 4 BP 1801 EP 1805 DI 10.1210/jc.86.4.1801 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 424QM UT WOS:000168243000060 PM 11297621 ER PT J AU Mandelbrot, DA Oosterwegel, MA Shimizu, K Yamada, A Freeman, GJ Mitchell, RN Sayegh, MH Sharpe, AH AF Mandelbrot, DA Oosterwegel, MA Shimizu, K Yamada, A Freeman, GJ Mitchell, RN Sayegh, MH Sharpe, AH TI B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CD28-DEFICIENT MICE; CARDIAC ALLOGRAFTS; ACTIVATION; MOLECULES; B7-1; DIFFERENTIATION; STIMULATION; SUFFICIENT; REJECTION; SURVIVAL AB To examine whether B7 costimulation can be mediated by a molecule on T cells that is neither CD28 nor CTLA4, we generated mice lacking both of these receptors, CD28/CTLA4(-/-) mice resemble CD28(-/-) mice in having decreased expression of T-cell activation markers in vivo and decreased T-cell proliferation in vitro, as compared with wild-type mice. Using multiple approaches, we find B7-dependent costimulation in CD28/CTLA4-/- mice. The proliferation of CD28/CTLA4(-/-) T cells is inhibited by CTLA4-Ig and by the use of antigen-presenting cells lacking both B7-1 and B7-2, CD28/CTLA4(-/-) T-cell proliferation is increased by exposure to Chinese hamster ovary cells transfected with B7-1 or B7-2. Finally, administration of CTLA4-Ig to CD28/CTLA4(-/-) cardiac allograft recipients significantly prolongs graft survival. These data support the existence of an additional receptor for B7 molecules that is neither CD28 nor CTLA4. C1 Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Utrecht, Med Ctr, Dept Immunol, Utrecht, Netherlands. RP Sharpe, AH (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-75174]; NHLBI NIH HHS [HL 43364]; NIAID NIH HHS [P01 AI039671, P01 AI041521, R37 AI038310, AI-39671, R01 AI034965, AI-34965, AI-38310, AI-41584, AI-41521, R01 AI038310] NR 24 TC 62 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 APR PY 2001 VL 107 IS 7 BP 881 EP 887 DI 10.1172/JCI11710 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 418DN UT WOS:000167875800018 PM 11285307 ER PT J AU Sakai, Y Kishimoto, J Demay, MB AF Sakai, Y Kishimoto, J Demay, MB TI Metabolic and cellular analysis of alopecia in vitamin D receptor knockout mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MURINE HAIR CYCLE; HISTONE DEACETYLASE; TRANSCRIPTIONAL REPRESSION; CO-REPRESSOR; D DEFICIENCY; N-COR; FOLLICLE; RICKETS; DIFFERENTIATION; GENE AB Targeted ablation of the vitamin D receptor (VDR) results in hypocalcemia, hypophosphatemia, hyperparathyroidism, rickets, osteomalacia, and alopecia - the last a consequence of defective anagen initiation. To investigate whether the markedly elevated levels of 1,25-dihydroxyvitamin D led to the alopecia, we raised VDR-null mice in a ultraviolet light-free environment and fed them chow lacking vitamin D for five generations. Despite undetectable circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, alopecia persisted in the VDR-null mice, demonstrating that the alopecia was not secondary to toxic levels of 1,25-dihydroxyvitamin D interacting with an alternative receptor. Furthermore, alopecia was not seen in control littermates, suggesting that absence of ligand and absence of receptor cause different phenotypes. To identify the cell population responsible for the alopecia, we performed hair-reconstitution assays in nude mice and observed normal hair follicle morphogenesis, regardless of the VDR status of the keratinocytes and dermal papilla cells. However, follicles reconstituted with VDR-null keratinocytes demonstrated a defective response to anagen initiation. Hence, alopecia in the VDR-null mice is due to a defect in epithelial-mesenchymal communication that is required for normal hair cycling. Our results also identify the keratinocyte as the cell of origin of the defect and suggest that this form of alopecia is due to absence of ligand-independent receptor function. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Wellman 501,50 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-46974, R01 DK046974] NR 31 TC 86 Z9 89 U1 0 U2 1 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 APR PY 2001 VL 107 IS 8 BP 961 EP 966 DI 10.1172/JCI11676 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 423AD UT WOS:000168152000007 PM 11306599 ER PT J AU Kovacs, CS Manley, NR Moseley, JM Martin, TJ Kronenberg, HM AF Kovacs, CS Manley, NR Moseley, JM Martin, TJ Kronenberg, HM TI Fetal parathyroids are not required to maintain placental calcium transport SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HORMONE-RELATED PROTEIN; TARGETED DISRUPTION; PTH/PTHRP RECEPTOR; MOUSE; PTHRP; HYPERCALCEMIA; STIMULATION; EXPRESSION; METABOLISM; GLANDS AB We used Hoxa3 knockout mice and other mouse models to study the role of the fetal parathyroids in fetal calcium homeostasis. Hoxa3-null fetuses lack parathyroid glands, and absence of parathyroid hormone (PTH) was confirmed with a rodent PTH immunoradiometric assay. The ionized calcium level of Hoxa3-null fetuses was significantly lower than that of wild-type or heterozygous littermates or of the mother. Both the rate of placental calcium transfer and the plasma PTHrP level were normal in Hoxa3 mutants and their heterozygous siblings. Because we had previously observed an increase in placental calcium transfer in PTH/PTHrP receptor I-null (Pthr1-null) fetuses, we assayed plasma PTHrP in those mice. Prhr1-null fetuses had plasma PTHrP levels 11-fold higher than those of their littermates. Northern analysis, immunohistochemical, and in situ hybridization studies of Pthr1-null fetuses indicated that liver and placenta had increased expression of PTHrP. In summary, loss of fetal parathyroids in Hoxa3-null fetuses caused marked hypocalcemia but did not alter placental calcium transfer or the circulating PTHrP level. The findings in the Pthr1-null fetuses indicate that several tissues may contribute to the circulating PTHrP level in fetal mice. C1 Mem Univ Newfoundland, Fac Med Endocrinol, St Johns, NF A1B 3V6, Canada. Med Coll Georgia, Dept Pediat, Inst Mol Med & Genet, Augusta, GA 30912 USA. Univ Melbourne, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kovacs, CS (reprint author), Mem Univ Newfoundland, Fac Med Endocrinol, 300 Prince Philip Dr, St Johns, NF A1B 3V6, Canada. OI Kovacs, Christopher/0000-0002-5219-9993 FU NIDDK NIH HHS [DK-47038] NR 20 TC 52 Z9 52 U1 0 U2 1 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 APR PY 2001 VL 107 IS 8 BP 1007 EP 1015 DI 10.1172/JCI11321 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 423AD UT WOS:000168152000012 PM 11306604 ER PT J AU Clarridge, JE Attorri, SM Zhang, Q Bartell, J AF Clarridge, JE Attorri, SM Zhang, Q Bartell, J TI 16S ribosomal DNA sequence analysis distinguishes biotypes of Streptococcus bovis: Streptococcus bovis biotype II/2 is a separate genospecies and the predominant clinical isolate in adult males SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IDENTIFICATION AB We characterized 22 human clinical strains of Streptococcus bovis by genotypic (16S rRNA gene sequence analysis [MicroSeq]; Applied Biosystems, Foster City, Calif,) and phenotypic (API 20 Strep and Rapid ID32 Strep systems (bioMerieux Vitek, Hazelton, Mo.) methods. The strains, isolated from blood, cerebrospinal fluid (CSF), and urine, formed two distinct 16S ribosomal DNA sequence clusters, Three strains which were associated with endocarditis urinary tract infection (UTI), and sepsis clustered with the S, bovis type strain ATCC 33317 (cluster 1); other closely related type strains were S, equinus and S. infantarius. Nineteen strains clustered at a distance of about 2.5% dissimilarity to the S. bovis type strain (cluster 2) and were associated with central nervous system (CNS) disease in addition to endocarditis, UTI, and sepsis, All strains were distinct front S, gallolyticus. Within cluster 2, a single strain grouped with ATCC strain 43143 (cluster 2a) and may be phenotypically distinct, All the other strains formed a second subgroup (cluster 2b) that was biochemically similar to S, bovis biotype II/2 (mannitol negative and beta galactosidase, alpha galactosidase, beta glucuronidase, and trehalose positive). The API 20 Strep system identified isolates of cluster 2b as S, bovis biotype II/2, those of cluster 1 as S, bovis biotype II/1, and that of cluster 2a as S, bovis biotype I. There was an excellent col,1,elation of biotype and genotype: S, bovis biotype II/2 isolates form a separate genospecies distinct from the S, bovis, S. gallolyticus, and S, infantarius type strains and are the most common isolates in adult males. C1 VA Med Ctr, Pathol & Lab Med Serv 113, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. MIDI Inc, Newark, DE USA. RP Clarridge, JE (reprint author), VA Med Ctr, Pathol & Lab Med Serv 113, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 10 TC 41 Z9 43 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2001 VL 39 IS 4 BP 1549 EP 1552 DI 10.1128/JCM.39.4.1549-1552.2001 PG 4 WC Microbiology SC Microbiology GA 419JX UT WOS:000167946500057 PM 11283085 ER PT J AU Fox, JG Handt, L Sheppard, BJ Xu, S Dewhirst, FE Motzel, S Klein, I AF Fox, JG Handt, L Sheppard, BJ Xu, S Dewhirst, FE Motzel, S Klein, I TI Isolation of Helicobacter cinaedi from the colon, liver, and mesenteric lymph node of a rhesus monkey with chronic colitis and hepatitis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TAMARINS SAGUINUS-OEDIPUS; CHRONIC ACTIVE HEPATITIS; CAMPYLOBACTER-CINAEDI; SP-NOV; HOMOSEXUAL MEN; BACTEREMIA; MICE; FENNELLIAE; INFECTION; CELLULITIS AB On the basis of biochemical, phenotypic, and 16S rRNA analyses, Helicobacter cinaedi was isolated front the colon, liver, and mesenteric lymph nodes of a 2-year-old rhesus monkey with chronic diarrhea, Histologically, the liver had mild to moderate biliary hyperplasia and hypertrophy with periportal inflammation and fibrosis. Colonic and cecal lesions consisted of diffuse chronic inflammation and glandular hyperplasia extending the length of the crypts. This is the first observation of H. cinaedi associated with active hepatitis and colitis In a nonhuman primate. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Merck Res Labs, W Point, PA 19468 USA. Forsyth Inst, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Rm 825C, Cambridge, MA 02139 USA. FU NCI NIH HHS [R01CA67529, R01 CA067529]; NIDDK NIH HHS [R01 DK052413, R01DK52413] NR 29 TC 60 Z9 62 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2001 VL 39 IS 4 BP 1580 EP 1585 DI 10.1128/JCM.39.4.1580-1585.2001 PG 6 WC Microbiology SC Microbiology GA 419JX UT WOS:000167946500063 PM 11283091 ER PT J AU Casarett, D Abrahm, JL AF Casarett, D Abrahm, JL TI Patients with cancer referred to hospice versus a bridge program: Patient characteristics, needs for care, and survival SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHYSICIAN-ASSISTED SUICIDE; TERMINALLY ILL PATIENTS; ELDERLY PATIENTS; CONTROLLED TRIAL; PALLIATIVE CARE; PAIN; QUALITY; LIFE; END; CONSULTATION AB Purpose: The purpose of this study was to compare the characteristics and needs of patients with advanced cancer who were referred to hospice with those referred to a prehospice "bridge" program that is staffed by hospice nurses. Patients and Methods: Data were gathered through retrospective review of computerized clinical records using preceded data fields of 284 patients with cancer enrolled in a bridge program and 1,000 who enrolled in a hospice program, Patient characteristics, needs for supportive care at the time of enrollment, and survival were assessed. Results: Bridge patients were less likely to have Medicare or Medicaid (43% v 72%; odds ratio, 0.30; P < .001) and were younger (69 v 73 years, rank sum test; P < .001), more likely to be married (59% v 43%; odds ratio, 1.90; P < .001), and more likely to be in the highest income category (14% v 10%; odds ratio, 1.77 P = .009). Bridge patients had at least as many needs for care as did patients in hospice, Bridge patients lived significantly longer (median, 46 v 19 days; log-rank test of survivor functions, P < .001). Conclusion: Patients referred to this bridge program had prognoses that are significantly better than those of patients who enter hospice, but they have needs for supportive care that are at least as great. These findings underscore the importance of initiatives to extend some of the benefits of hospice care to a wider population of patients and should encourage the analysis of similar programs' ability to meet these needs. (C) 2001 by American Society of Clinical Oncology. C1 Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Bioeth, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia Vet Affairs Med Ctr, Dept Med, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia Vet Affairs Med Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA. RP Casarett, D (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Bioeth, Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 43 TC 29 Z9 29 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2001 VL 19 IS 7 BP 2057 EP 2063 PG 7 WC Oncology SC Oncology GA 418XT UT WOS:000167920300022 PM 11283139 ER PT J AU Paz-Ares, L Olivia, E Carey, RW Smith, MR AF Paz-Ares, L Olivia, E Carey, RW Smith, MR TI Skin lesions in malignancy case 2. Skin metastases from prostate adenocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Paz-Ares, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2001 VL 19 IS 7 BP 2099 EP 2100 PG 2 WC Oncology SC Oncology GA 418XT UT WOS:000167920300028 PM 11283145 ER PT J AU Haffajee, AD Socransky, SS AF Haffajee, AD Socransky, SS TI Relationship of cigarette smoking to attachment level profiles SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE smoking; periodontal diseases; periodontitis; pocket depth; attachment level ID DWELLING OLDER ADULTS; ALVEOLAR BONE LEVELS; PERIODONTAL-DISEASE; RISK INDICATORS; SMOKERS; INDIVIDUALS; POPULATION; NONSMOKERS; CALCULUS; GENOTYPE AB Objectives: The present investigation examined clinical features of periodontal disease and patterns of attachment loss in adult periodontitis subjects who were current, past or never smokers. Material and Methods: 289 adult periodontitis subjects ranging in age from 20-86 years with at least 20 teeth and at least 4 sites with pocket depth and/or attachment level >4 mm were recruited. Smoking history was obtained using a questionnaire. Measures of plaque accumulation, overt gingivitis, bleeding on probing, suppuration, probing pocket depth and probing attachment level were taken at 6 sites per tooth at all teeth excluding 3rd molars at a baseline visit. Subjects were subset according to smoking history into never, past and current smokers and for certain analyses into age categories <41, 41-49, >49. Uni- and multi-variate analyses examined associations between smoking category, age and clinical parameters. Results: Current smokers had significantly more attachment loss, missing teeth, deeper pockets and fewer sites exhibiting bleeding on probing than past or never smokers. Current smokers had greater attachment loss than past or never smokers whether the subjects had mild, moderate or severe initial attachment loss. Increasing age and smoking status were independently significantly related to mean attachment level and the effect of these parameters was additive. Mean attachment level in non smokers <41 years and current smokers >49 years was 2.49 and 4.10 mm respectively. Stepwise multiple linear regression indicated that age, pack years and being a current smoker were strongly associated with mean attachment level. Full mouth attachment level profiles indicated that smokers had more attachment loss than never smokers particularly at maxillary lingual sites and at lower anterior teeth. Conclusions: In accord with other studies, smokers had evidence of more severe periodontal disease than past or never smokers. At all levels of mean attachment loss, smokers exhibited more disease than never smokers. Difference in mean attachment level between smokers and never smokers at individual sites was not uniform. Significantly more loss was observed at maxillary lingual sites and lower anterior teeth suggesting the possibility of a local effect of cigarette smoking. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 The Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10977, DE-12108, DE-12861] NR 40 TC 105 Z9 117 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD APR PY 2001 VL 28 IS 4 BP 283 EP 295 DI 10.1034/j.1600-051x.2001.028004283.x PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 414XR UT WOS:000167691900001 PM 11314883 ER PT J AU Stewart, JE Wager, KA Friedlander, AH Zadeh, HH AF Stewart, JE Wager, KA Friedlander, AH Zadeh, HH TI The effect of periodontal treatment on glycemic control in patients with type 2 diabetes mellitus SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE adult periodontitis; root planing; subgingival curettage; type 2 diabetes mellitus; glycemic control; hemoglobin A(1C) ID DISEASE AB Background, aims: This study was designed to explore the effect of periodontal therapy on glycemic control in persons with type 2 diabetes mellitus (DM). Methods: 36 patients with type 2 DM (treatment group) received therapy for adult periodontitis during an Is-month period. A 36-person control group was randomly selected from the same population of persons with type 2 DM who did not receive periodontal treatment. Results: These groups were well matched for most of the parameters investigated. During the nine-month observation period, there was a 6.7% improvement in glycemic control in the control group when compared to a 17.1% improvement in the treatment group, a statistically significant difference. Several parameters that could confound or moderate this glycemic control were explored. These included the treatment of non-dental infections, weight and medication changes. No moderating effect was associated with any of these variables. However, there were too few subjects in the study to have the statistical power necessary to assess these possible moderators of glycemic control. Conclusions: We interpret the data in the study to suggest that periodontal therapy was associated with improved glycemic control in persons with type 2 DM. C1 VA Greater LA Hlth Care Syst, Dent Serv, Los Angeles, CA 90012 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. Univ So Calif, Sch Dent, Dept Periodontol, Los Angeles, CA 90089 USA. RP Stewart, JE (reprint author), VA Greater LA Hlth Care Syst, Dent Serv, 351 E Temple St, Los Angeles, CA 90012 USA. NR 27 TC 124 Z9 140 U1 1 U2 9 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD APR PY 2001 VL 28 IS 4 BP 306 EP 310 DI 10.1034/j.1600-051x.2001.028004306.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 414XR UT WOS:000167691900003 PM 11314885 ER PT J AU Pettinati, HM Volpicelli, JR Luck, G Kranzler, HR Rukstalis, MR Cnaan, A AF Pettinati, HM Volpicelli, JR Luck, G Kranzler, HR Rukstalis, MR Cnaan, A TI Double-blind clinical trial of sertraline treatment for alcohol dependence SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 11-18, 1998 CL LOS CROABAS, PUERTO RICO SP Amer Coll Neuropsychopharmacol ID PLACEBO-CONTROLLED TRIAL; CONSUMMATORY BEHAVIORS; ETHANOL INTAKE; FLUOXETINE; PHARMACOTHERAPY; CONSUMPTION; MEDICATION; DRINKERS AB Clinical studies that have evaluated serotonergic medications to reduce alcohol consumption have yielded conflicting results. These studies primarily treated patients with alcohol dependence, excluding those with a current depressive disorder, in an effort to differentiate any medication effects directly on drinking from those on mood. Yet despite the exclusion of current depression, a group of alcohol-dependent patients who are not depressed can be highly heterogeneous. For example, this subgroup can include those with a Lifetime depressive disorder. If these patients were more sensitive to serotonergic medications than patients without a Lifetime depressive disorder, medication effects in a subgroup of patients who were not depressed could be obscured. Thus, the purpose of this study was to examine the efficacy of sertraline for treating alcohol dependence in patient groups that were differentiated by the presence or absence of Lifetime depression. This study examined the effectiveness of sertraline (200 mg/day) or placebo for 14 weeks in 100 alcohol-dependent subjects with (N = 53) or without (N = 47) a lifetime diagnosis of comorbid depression. Sertraline treatment seemed to provide an advantage in reducing drinking in alcohol-dependent patients without lifetime depression, illustrated best with a measure of drinking frequency during treatment. However, sertraline was no better than placebo in patients with a diagnosis of lifetime comorbid depression, and current depression did not change the results. Treatment with selective serotonin reuptake inhibitors may be useful in alcohol-dependent patients who are not depressed. Subtyping those with alcohol dependence on the basis of the absence versus the presence of a Lifetime depressive disorder may help to resolve conflicting findings in the literature on the treatment of alcohol dependence with serotonergic medications. C1 Univ Penn, Addict Treatment Res Ctr, Sch Med, Dept Psychiat,Ctr Study Addict, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Connecticut, Sch Med, Dept Psychiat, Alcohol Res Ctr, Farmington, CT USA. RP Pettinati, HM (reprint author), Univ Penn, Addict Treatment Res Ctr, Sch Med, Dept Psychiat,Ctr Study Addict, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIAAA NIH HHS [K02-AA 00239, R01-AA09544] NR 27 TC 89 Z9 92 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2001 VL 21 IS 2 BP 143 EP 153 DI 10.1097/00004714-200104000-00005 PG 11 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 412RV UT WOS:000167568900005 PM 11270910 ER PT J AU Roberts, A Chapple, ILC Matthews, JB Freestone, PP Socransky, SS AF Roberts, A Chapple, ILC Matthews, JB Freestone, PP Socransky, SS TI Growth response of oral Streptococci to catecholamines SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Inst, Boston, MA USA. Univ Leicester, Dept Microbiol, Leicester, Leics, England. Sch Dent, Birmingham, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2001 VL 80 IS 4 BP 1169 EP 1169 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 497VL UT WOS:000172476101605 ER PT J AU Stein, MT Katz, RM Jellinek, MS Cassidy, L Olness, K AF Stein, MT Katz, RM Jellinek, MS Cassidy, L Olness, K TI Cyclic vomiting SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material ID MIGRAINE C1 Univ Calif San Diego, Sch Med, Div Primary Care Pediat & Adolescent Med, San Diego, CA 92103 USA. Kennedy Krieger Inst, Feeding Disorders Program, Baltimore, MD USA. Johns Hopkins Univ, Div Pediat Gastroenterol & Nutr, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Case Western Reserve Univ, Sch Med, Div Gen Acad Pediat, Cleveland, OH USA. RP Stein, MT (reprint author), Univ Calif San Diego, Sch Med, Div Primary Care Pediat & Adolescent Med, San Diego, CA 92103 USA. NR 18 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD APR PY 2001 VL 22 IS 2 SU S BP S139 EP S142 PG 4 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 423NV UT WOS:000168183100027 PM 11332794 ER PT J AU Filbin, MR Brown, DFM Nadel, ES Benzer, T Nagurney, JT Gordon, J Tancredi, D AF Filbin, MR Brown, DFM Nadel, ES Benzer, T Nagurney, JT Gordon, J Tancredi, D TI Hyperglycemic hyperosmolar nonketotic coma SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID SEVERE DIABETIC-KETOACIDOSIS; BICARBONATE THERAPY; MANAGEMENT; IMPROVE C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, CLN-115, Boston, MA 02114 USA. NR 14 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 APR PY 2001 VL 20 IS 3 BP 285 EP 290 DI 10.1016/S0736-4679(01)00283-9 PG 6 WC Emergency Medicine SC Emergency Medicine GA 413BL UT WOS:000167590000011 PM 11267819 ER PT J AU Gordon, AJ Maisto, SA McNeil, M Kraemer, KL Conigliaro, RL Kelley, ME Conigliaro, J AF Gordon, AJ Maisto, SA McNeil, M Kraemer, KL Conigliaro, RL Kelley, ME Conigliaro, J TI Three questions can detect hazardous drinkers SO JOURNAL OF FAMILY PRACTICE LA English DT Article DE alcohol drinking; mass screening; alcoholism; questionnaires ID ALCOHOL-USE DISORDERS; IDENTIFICATION TEST AUDIT; RANDOMIZED CONTROLLED TRIAL; PRIMARY-CARE PATIENTS; SCREENING QUESTIONNAIRES; COLLABORATIVE PROJECT; BRIEF INTERVENTIONS; PROBLEM DRINKING; CONSUMPTION; CAGE AB OBJECTIVE We evaluated the Alcohol Use Disorders Identification Test (AUDIT), the first 3 questions of the AUDIT (AUDIT-C), the third AUDIT question (AUDIT-S), and quantity-frequency questions for identifying hazardous drinkers in a large primary care sample. STUDY DESIGN Cross-sectional survey. POPULATION Patients waiting for care at 12 primary care sites in western Pennsylvania from October 1995 to December 1997. OUTCOMES MEASURED Sensitivity, specificity, likelihood ratios, and predictive values for the AUDIT, AUDIT-C, and AUDIT-S. RESULTS A total of 13,438 patients were surveyed. Compared with a quantity-frequency definition of hazardous drinking (greater than or equal to 16 drinks/week for men and 112 drinks/week for women), the AUDIT, AUDIT-C, and AUDIT-S had areas under the receiver-operating characteristic curves (AUROC) of 0.940, 0.949, and 0.871, respectively. The AUROCs of the AUDIT and AUDIT-C were significantly different (P=.004). The AUROCs of the AUDIT-C (P <.001) and AUDIT (P <.001) were significantly larger than the AUDIT-3. When compared with a positive AUDIT score of 8 or higher, the AUDIT-C (score greater than or equal to3) and the AUDIT-3 (score greater than or equal to1) were 94.9% and 99.6% sensitive and 68.8% and 51.1% specific in detecting individuals as hazardous drinkers. CONCLUSIONS In a large primary care sample, a 3-question version of the AUDIT identified hazardous drinkers as well as the full AUDIT when such drinkers were defined by quantity-frequency criterion. This version of the AUDIT may be useful as an initial screen for assessing hazardous drinking behavior. C1 VA Pittsburgh Hlth Care Syst, VA Pittsburgh Ctr Hlth Serv Res, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. RP Gordon, AJ (reprint author), VA Pittsburgh Hlth Care Syst, VA Pittsburgh Ctr Hlth Serv Res, Room 11E-118 130-U,Univ Dr C, Pittsburgh, PA 15240 USA. FU NIAAA NIH HHS [AA00235, AA10291] NR 42 TC 136 Z9 137 U1 3 U2 9 PU DOWDEN PUBLISHING CORP PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD APR PY 2001 VL 50 IS 4 BP 313 EP 320 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 421AV UT WOS:000168040700006 PM 11300982 ER PT J AU Goodson, JD Bierman, AS Fein, O Rask, K Rich, EC Selker, HP AF Goodson, JD Bierman, AS Fein, O Rask, K Rich, EC Selker, HP TI The future of capitation - The physician role in managing change in practice SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE capitation; physician reimbursement; physician organization; physician financial risk; universal health care access ID FEE-FOR-SERVICE; HEALTH MAINTENANCE ORGANIZATIONS; PREPAID GROUP-PRACTICE; PRIMARY-CARE; MEDICAL OUTCOMES; FINANCIAL INCENTIVES; RISK-ADJUSTMENT; RANDOMIZED TRIAL; SYSTEMS; PAYMENT AB Capitation-based reimbursement significantly influences the practice of medicine. As physicians, we need to assure that payment models do not jeopardize the care we provide when we accept higher levels of personal financial risk. In this paper, we review the literature relevant to capitation, consider the interaction of financial incentives with physician and medical risk, and conclude that primary care physicians need to work to assure that capitated systems incorporate checks and balances that protect both patients and providers, We offer the following proposals for individuals and groups considering capitated contracts: (1) reimbursement for primary care physicians should recognize both individual patient encounters and the administrative work of patient care management; (2) reimbursement for subspecialists should recognize both access to subspecialty knowledge and expertise as well as patient care encounters, but in some situations, subspecialists may provide the majority of care to individual patients and will be reimbursed as primary care providers; (3) groups of physicians should accept financial risk for patient care only if they have the tools and resources to manage the care; (4) physicians sharing risk for patient care should meet regularly to discuss care and resource management; and (5) physicians must disclose the financial relationships they have with health plans and medical care organizations. and engage patients and communities in discussions about resource allocation. As a payment model, capitation offers opportunities for primary care physicians to influence the future of health care by improving the management of resources at a local level. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. US Dept HHS, Agcy Hlth Care Policy & Res, Ctr Outcomes & Effectiveness Res, Rockville, MD 20852 USA. Cornell Univ, Weill Med Coll, Dept Clin Med & Clin Publ Hlth, New York, NY USA. Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. Creighton Univ, Sch Med, Dept Med, Ctr Practice Improvement & Outcomes Res, Omaha, NE USA. New England Med Ctr, Div Clin Care Res, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. RP Goodson, JD (reprint author), Massachusetts Gen Hosp, WAC 625, Boston, MA 02114 USA. RI rask, kimberly/M-8001-2016 NR 60 TC 14 Z9 14 U1 0 U2 1 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 APR PY 2001 VL 16 IS 4 BP 250 EP 256 DI 10.1046/j.1525-1497.2001.016004250.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 420GH UT WOS:000167996900006 PM 11318926 ER PT J AU West, CA He, CF Su, M Swanson, SJ Mentzer, SJ AF West, CA He, CF Su, M Swanson, SJ Mentzer, SJ TI Aldehyde fixation of thiol-reactive fluorescent cytoplasmic probes for tracking cell migration SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE fluorescent dyes; cell migration; aldehydes; histocytochemistry; fluorescence cytometry ID PHOTOBLEACHING KINETICS; PERITONEAL-MACROPHAGES; INVIVO; LYMPHOCYTES; MICROSCOPY; STATE AB Tracking of cell migration plays an important role in the study of morphogenesis, inflammation, and metastasis. The recent development of probes that exist as intracellular peptide-fluorescence dye adducts has offered the possibility of aldehyde fixation of these dyes for detailed anatomic studies of lymphocyte trafficking. To define the conditions for fixation of these cytoplasmic fluorescent probes, we compared fixation conditions containing formaldehyde, glutaraldehyde, paraformaldehyde, zinc formaldehyde, and glyoxylate,as well as fixation by quick-freezing in liquid nitrogen-cooled methylbutane. The efficacy of aldehyde fixation of the cell fluorescence was assessed by quantitative tissue cytometry and flow cytometry. We studied cytoplasmic fluorescent dyes with discrete emissions in the green [5-chloromethylfluorescein diacetate (CMFDA); 492 ex, 516 em] and orange [5-(and-6)-(4-chloromethyl(benzoyl)amino) tetramethylrhodamine (CMTMR); 540 ex. 566 em] spectra. The results demonstrated that aldehyde fixation preserved cell fluorescence for more than 6 months. The primary difference between the aldehyde fixatives was variability in the difference between the yield of the cell fluorescence and the relevant background fluorescence. Formaldehyde and paraformaldehyde were superior to the other fixatives in preserving cell fluorescence while limiting background fluorescence. With these fixatives, both the CMFDA and CMTMR fluorescent dyes permitted sufficient anatomic resolution for reliable localization in long-term cell tracking studies. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Immunophysiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Immunophysiol Lab, 75 Francis St,PBB Lobby, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL47078] NR 33 TC 14 Z9 14 U1 1 U2 11 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD APR PY 2001 VL 49 IS 4 BP 511 EP 517 PG 7 WC Cell Biology SC Cell Biology GA 422TR UT WOS:000168135800011 PM 11259454 ER PT J AU Cross, AS Opal, SM Warren, HS Palardy, JE Glaser, K Parejo, NA Bhattacharjee, AK AF Cross, AS Opal, SM Warren, HS Palardy, JE Glaser, K Parejo, NA Bhattacharjee, AK TI Active immunization with a detoxified Escherichia coli J5 lipopolysaccharide group B meningococcal outer membrane protein complex vaccine protects animals from experimental sepsis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NEGATIVE BACTERIAL SEPSIS; DOUBLE-BLIND; MONOCLONAL-ANTIBODY; SEPTIC SHOCK; BACTEREMIA; MUTANT; ANTISERUM; TRIAL; IGG; INFECTION AB The passive infusion of antibodies elicited in rabbits with a detoxified J5 lipopolysaccharide (LPS)/group B meningococcal outer membrane protein complex vaccine protected neutropenic rats from heterologous lethal gram-negative bacterial infection. In this study, active immunization was studied in neutropenic rats infected with Pseudomonas aeruginosa, in the presence or absence of ceftazidime therapy, and with Klebsiella pneumoniae. This vaccine elicited a >200-fold increase in anti-J5 LPS antibody, which remained elevated throughout the duration of cyclophosphamide-induced neutropenia and for less than or equal to3 months. There was improved survival among immunized versus control animals: 48% (13/28) versus 7% (2/29) in Pseudomonas-challenged rats; 61% (11/18) versus 0% (0/10) in Pseudomonas- and ceftazdime-treated rats; and 64% (9/14) versus 13% (2/15) in Klebsiella-challenged rats (P < .01 for each comparison). Immunized animals had lower levels of bacteria in organs and lower levels of circulating endotoxin at the onset of fever. In conclusion, active immunization with an anti-endotoxin vaccine improved survival after infection with 2 heterologous, clinically relevant bacterial species in immunocompromised animals. Active immunization with this vaccine merits further investigation. C1 Univ Maryland, Sch Med, Dept Med, Div Infect Dis,MSTF, Baltimore, MD 21201 USA. Walter Reed Army Inst Res, Dept Bacterial Dis, Silver Spring, MD USA. Brown Univ, Sch Med, Dept Med, Div Infect Dis, Providence, RI 02912 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA USA. RP Cross, AS (reprint author), Univ Maryland, Sch Med, Dept Med, Div Infect Dis,MSTF, Ste 900,10 S Pine St, Baltimore, MD 21201 USA. FU NIAID NIH HHS [R01 AI42181] NR 30 TC 26 Z9 27 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2001 VL 183 IS 7 BP 1079 EP 1086 DI 10.1086/319297 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 409CL UT WOS:000167366900012 PM 11237833 ER PT J AU Baehring, JM Alemohammed, S Croul, SE AF Baehring, JM Alemohammed, S Croul, SE TI Malignant fibrous histiocytoma presenting as an intraventricular mass five years after incidental detection of a mass lesion SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE malignant fibrous histiocytoma; intracranial; intraventricular ID SARCOMAS; FEATURES AB Malignant fibrous histiocytoma is a rare intracranial neoplasm. It usually presents as a meningeal mass but occurs also intraaxially. Few information is available on cellular origin, premalignant histologic stages and time course of malignant transformation. We report a case of a primary intraventricular malignant fibrous histiocytoma in a patient who five years prior to clinical manifestation of the malignancy was found to have an intraventricular mass with benign CT characteristics. C1 MCP Hahnemann Univ, Dept Neurol, Philadelphia, PA USA. MCP Hahnemann Univ, Dept Neurosurg, Philadelphia, PA USA. MCP Hahnemann Univ, Dept Pathol, Philadelphia, PA USA. RP Baehring, JM (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Cox Bldg,Suite 315, Boston, MA 02114 USA. NR 17 TC 8 Z9 8 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD APR PY 2001 VL 52 IS 2 BP 157 EP 160 DI 10.1023/A:1010685020995 PG 4 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 446LU UT WOS:000169515400007 PM 11508815 ER PT J AU Andreassen, OA Jenkins, BG Dedeoglu, A Ferrante, KL Bogdanov, MB Kaddurah-Daouk, R Beal, MF AF Andreassen, OA Jenkins, BG Dedeoglu, A Ferrante, KL Bogdanov, MB Kaddurah-Daouk, R Beal, MF TI Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE creatine; glutamate; glutamate transport; oxidative damage; magnetic resonance spectroscopy ID CU/ZN-SUPEROXIDE-DISMUTASE; MOTOR-NEURON DISEASE; HUNTINGTONS-DISEASE; OXIDATIVE DAMAGE; FREE-RADICALS; MOUSE MODEL; ANIMAL-MODEL; TRANSPORTER; MUTATION; ALS AB Several lines of evidence implicate excitotoxic mechanisms in the pathogenesis of amyotrophic lateral sclerosis (ALS). Transgenic mice with a superoxide dismutase mutation (G93A) have been utilized as an animal model of familial ALS (FALS). We examined the cortical concentrations of glutamate using in vivo microdialysis and in vivo nuclear magnetic resonance (NMR) spectroscopy, and the effect of long-term creatine supplementation. NMDA-stimulated and L-trans-pyrrolidine-2,4-dicarboxylate (LTPD)-induced increases in glutamate were significantly higher in G93A mice compared with littermate wild-type mice at 115 days of age. At this age, the tissue concentrations of glutamate were also significantly increased as measured with NMR spectroscopy. Creatine significantly increased longevity and motor performance of the G93A mice, and significantly attenuated the increases in glutamate measured with spectroscopy at 75 days of age, but had no effect at 115 days of age. These results are consistent with impaired glutamate transport in G93A transgenic mice. The beneficial effect of creatine may be partially mediated by improved function of the glutamate transporter, which has a high demand for energy and is susceptible to oxidative stress. C1 Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Neurol & Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Avicena Grp, Cambridge, MA USA. RP Beal, MF (reprint author), Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Neurol & Neurosci, 525 E 68th St, New York, NY 10021 USA. FU NIA NIH HHS [P01 AG12992] NR 42 TC 73 Z9 74 U1 0 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2001 VL 77 IS 2 BP 383 EP 390 DI 10.1046/j.1471-4159.2001.00188.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 421PL UT WOS:000168072700003 PM 11299300 ER PT J AU Cho, HS Hyman, BT Greenberg, SM Rebeck, GW AF Cho, HS Hyman, BT Greenberg, SM Rebeck, GW TI Quantitation of apoE domains in Alzheimer disease brain suggests a role for apoE in A beta aggregation SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE amyloid; lipoprotein; proteolysis; receptor ID CEREBRAL AMYLOID ANGIOPATHY; APOLIPOPROTEIN-E EPSILON-2; PEPTIDE DEPOSITION; NEURONAL CULTURES; TYPE-4 ALLELE; E GENOTYPE; PROTEIN; RECEPTOR; BINDING; HEMORRHAGE AB Apolipoprotein E (apoE) and apoE-derived proteolytic fragments are present in amyloid deposits in Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). In this study, we examined which apoE fragments are most strongly associated with amyloid deposits and whether apoE receptor binding domains were present. We found that both apoE2- and apoE4-specific residues were present on plaques and blood vessels in AD and CAA. We quantified A beta plaque burden and apoE plaque burdens in 5 AD brains. ApoE N-terminal specific and C-terminal-specific antibodies covered 50% and 74% of A beta plaque burden, respectively (p < 0.003). Double-labeling demonstrated that the plaque cores contained the entire apoE protein, but that outer regions contained only a C-terminal fragment, suggesting a cleavage in the random coil region of apoE. Presence of N- and C-terminal apoE cleavage fragments in brain extracts was confirmed by immunoblotting. The numbers of plaques identified by the apoE N-terminal-specific antibodies and the apoE C-terminal-specific antibody were equal, but were only approximately 60% of the total A plaque number (p < 0.0001). Analysis of the size distribution of A and apoE deposits demonstrated that most of the A beta -positive, apoE-negative deposits were the smallest deposits (less than 150 mum(2)). These data suggest that C-terminal residues of apoE bind to A beta and that apoE may help aid in the progression of small A beta deposits to larger deposits. Furthermore, the presence of the apoE receptor binding domain in the center of amyloid deposits could affect surrounding cells via chronic interactions with cell surface apoE receptors. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG12406, AG00725, P50 AG05134] NR 47 TC 63 Z9 66 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD APR PY 2001 VL 60 IS 4 BP 342 EP 349 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 419HC UT WOS:000167942400004 PM 11305869 ER PT J AU Merfeld, DM Zupan, LH Gifford, CA AF Merfeld, DM Zupan, LH Gifford, CA TI Neural processing of gravito-inertial cues in humans. II. Influence of the semicircular canals during eccentric rotation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VERTICAL OPTOKINETIC NYSTAGMUS; VESTIBULOOCULAR REFLEX; LINEAR ACCELERATION; SQUIRREL-MONKEY; ROLL-TILT; OCULAR RESPONSES; VIEWING DISTANCE; EYE-MOVEMENTS; HEAD MOTION; PERCEPTION AB All linear accelerometers, including the otolith organs, respond equivalently to gravity and linear acceleration. To investigate how the nervous system resolves this ambiguity, we measured perceived roll tilt and reflexive eye movements in humans in the dark using two different centrifugation motion paradigms (fixed radius and variable radius) combined with two different subject orientations (facing-motion and back-to-motion). In the fixed radius trials, the radius at which the subject was seated was held constant while the rotation speed was changed to yield changes in the centrifugal force. In variable radius trials, the rotation speed was held constant while the radius was varied to yield a centrifugal force that nearly duplicated that measured during the fixed radius condition. The total gravito-inertial force (GIF) measured by the otolith organs was nearly identical in the two paradigms; the primary difference was the presence (fixed radius) or absence (variable radius) of yaw rotational cues. We found that the yaw rotational cues had a large statistically significant effect on the time course of perceived tilt, demonstrating that yaw rotational cues contribute substantially to the neural processing of roll tilt. We also found that the orientation of the subject relative to the centripetal acceleration had a dramatic influence on the eye movements measured during fixed radius centrifugation. Specifically, the horizontal vestibuloocular reflex (VOR) measured in our human subjects was always greater when the subject faced the direction of motion than when the subjects had their backs toward the motion during fixed radius rotation. This difference was consistent with the presence of a horizontal translational VOR response induced by the centripetal acceleration. Most importantly, by comparing the perceptual tilt responses to the eye movement responses, we found that the translational VOR component decayed as the subjective tilt indication aligned with the tilt of the GIF. This was true for both the fixed radius and variable radius conditions even though the time course of the responses was significantly different for these two conditions. These findings are consistent with the hypothesis that the nervous system resolves the ambiguous measurements of GIF into neural estimates of gravity and linear acceleration. More generally, these findings are consistent with the hypothesis that the nervous system uses internal models to process and interpret sensory motor cues. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. RP Merfeld, DM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Jenks Vestibular Physiol Lab, Suite 421,243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC-03066] NR 53 TC 67 Z9 67 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2001 VL 85 IS 4 BP 1648 EP 1660 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 418AB UT WOS:000167866700030 PM 11287488 ER PT J AU Howell, JN Frederick, J Olinger, B Leftridge, D Bell, T Hess, R Clipp, EC AF Howell, JN Frederick, J Olinger, B Leftridge, D Bell, T Hess, R Clipp, EC TI Can nurses govern in a government agency? SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID SHARED GOVERNANCE; MAGNET HOSPITALS; INSTITUTIONS; EXCELLENCE; VISION AB A shared governance model was implemented within the nursing service of the Durham Veterans Affairs Medical Center in 1997. In 1999, a members of the Nursing Quality/Staff Education/Research Council examined facility nurses' perceptions of governance to determine the degree to which the model had been implemented. Results of the study indicate that although imperatives at the organizational level were incompatible with three aspects of shared governance, there were three shared governance dimensions pertaining to basic nursing practice that reached or surpassed governance thresholds. his study highlights the potential of nursing management innovation within highly bureaucratic organizations. C1 Durham Vet Affairs Med Ctr, Educ & Clin Ctr, Durham, NC USA. Houston VAMC, Houston, TX USA. Nursing Spectrum, King Of Prussia, PA USA. Duke Univ, Dept Med, Med Ctr, Durham, NC 27706 USA. RP Howell, JN (reprint author), Durham Vet Affairs Med Ctr, Educ & Clin Ctr, Durham, NC USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD APR PY 2001 VL 31 IS 4 BP 187 EP 195 DI 10.1097/00005110-200104000-00007 PG 9 WC Nursing SC Nursing GA 424WX UT WOS:000168257900007 PM 11324331 ER PT J AU Buckley, TC Parker, JD Heggie, J AF Buckley, TC Parker, JD Heggie, J TI A psychometric evaluation of the BDI-II in treatment-seeking substance abusers SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Beck Depression inventory-II; substance abuse; psychometric; factor analysis ID BECK-DEPRESSION INVENTORY; PSYCHIATRIC OUTPATIENTS; COMORBIDITY; ANXIETY AB The Beck Depression Inventory-II (BDI-II) was administered to 416 consecutive male admissions to a 28-day residential chemical dependence treatment program as part of a routine intake procedure. Psychometric analyses revealed that the BDI-II scores were internally consistent in this treatment-seeking population based on coefficient alpha. The mean BDI-II score for patients in this study was higher than that noted for other clinical samples in previous studies. The use of the BDI-II for clinical decision making with chemically dependent individuals is discussed in light of this elevated distribution of scores. Confirmatory factor-analytic examinations of the instrument revealed that a three-factor model, with cognitive, affective, and somatic symptoms loading as separate factors, provided the most adequate account of the data. In total, the study supported the use of the BDI-II for the assessment of depression in chemically dependent male patients entering a residential treatment program at a VAMC facility, provided population-specific normative data is utilized for making clinical decisions. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Boston Vet Affairs Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. GV Sonny Montgomery Vet Affairs Med Ctr, Montgomery, AL USA. Univ Mississippi, Med Ctr, Mississippi State, MS USA. RP Buckley, TC (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02131 USA. NR 27 TC 75 Z9 75 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2001 VL 20 IS 3 BP 197 EP 204 DI 10.1016/S0740-5472(00)00169-0 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 441NQ UT WOS:000169236800001 PM 11516588 ER PT J AU Guo, SS Wu, XY Shimoide, AT Wong, J Sawicki, MP AF Guo, SS Wu, XY Shimoide, AT Wong, J Sawicki, MP TI Anomalous overexpression of p27(Kip1) in sporadic pancreatic endocrine tumors SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 24th Annual Symposium of the Association-of-Veterans-Administration-Surgeons CY APR 09-11, 2000 CL SEATTLE, WASHINGTON SP Assoc Vet Adm Surgeons DE p27(Kip1); pancreas; endocrine tumors; prognosis; cell cycle regulation; tumorigenesis; islets of Langerhans ID DEPENDENT KINASE INHIBITOR; CYCLIN D1; PROGNOSTIC-SIGNIFICANCE; EXPRESSION; CARCINOMA; CANCER; GENE; P27; RECURRENCE; PREDICTS AB Background. Little is known about the cellular defects and molecular mechanisms leading to pancreatic endocrine tumors (PETs). p27(Kip1), a universal cyclin-dependent kinase inhibitor (CDKI), which acts as a tumor suppressor and a negative regulator of cell cycle. From previous reports, quiescent cells show high levels of p27(Kip1) expression while neoplastic and proliferating cells show no detectable p27(Kip)1 expression. We hypothesize that in malignant sporadic PETs, p27(Kip1) expression would be decreased compared with benign PETs and normal pancreatic tissue. Methods. Western analysis was performed on 28 PETs (7 malignant, 21 benign), 2 nonendocrine cell lines, and 5 endocrine cell lines, Signal intensities were quantitated using densitometry and standardized to normal pancreas. Results. Unexpectedly, increased p27(Kip1) expression as compared with control was seen in both benign and malignant tumors, as well as in all four pancreatic islet tumor cell lines, but not fibroblast or pituitary cell lines, evaluated. There was no difference in p27(Kip1) level between benign and malignant tumors. Conclusion. This represents the first report of anomalous p27(Kip1) overexpression in sporadic PETs, and is part of a growing literature describing the paradoxical overexpression of p27(Kip1) in human tumors that includes other endocrine tumors. These studies suggest a unique molecular pathway leading to endocrine tumorigenesis. (C) 2001 Academic Press. C1 Univ Calif Los Angeles, Sch Med, Div Gen Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Dept Surg, Los Angeles, CA USA. RP Sawicki, MP (reprint author), Univ Calif Los Angeles, Sch Med, Div Gen Surg, Room 72-215 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 21 TC 22 Z9 23 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 APR PY 2001 VL 96 IS 2 BP 284 EP 288 DI 10.1006/jsre.2001.6085 PG 5 WC Surgery SC Surgery GA 421TT UT WOS:000168080200021 PM 11266285 ER PT J AU Christian, M Yeung, L Williams, R Moy, R AF Christian, M Yeung, L Williams, R Moy, R TI Conscious sedation in dermatologic surgery SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article C1 Univ Texas, SW Med Ctr, Dept Dermatol, Dallas, TX 75216 USA. Journal Dermatol Surg, Los Angeles, CA 90027 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. RP Christian, M (reprint author), Univ Texas, SW Med Ctr, Dept Dermatol, Dallas, TX 75216 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2001 VL 44 IS 4 BP 665 EP 670 DI 10.1067/mjd.2001.113607 PG 6 WC Dermatology SC Dermatology GA 416EU UT WOS:000167768000018 PM 11260544 ER PT J AU Kobayashi, Y Honda, Y Christie, LG Teirstein, PS Bailey, SR Brown, CL Matthews, RV De Franco, AC Schwartz, RS Goldberg, S Popma, JJ Yock, PG Fitzgerald, PJ AF Kobayashi, Y Honda, Y Christie, LG Teirstein, PS Bailey, SR Brown, CL Matthews, RV De Franco, AC Schwartz, RS Goldberg, S Popma, JJ Yock, PG Fitzgerald, PJ TI Long-term vessel response to a self-expanding coronary stent: A serial volumetric intravascular ultrasound analysis from the ASSURE trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PALMAZ-SCHATZ STENTS; NEOINTIMAL HYPERPLASIA; IMAGING CATHETER; NITINOL STENTS; BALLOON INJURY; FOLLOW-UP; RESTENOSIS; PROLIFERATION; ANGIOPLASTY; MODEL AB OBJECTIVES We sought to investigate the in vivo mechanical properties of a new self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel response over time. BACKGROUND Preclinical studies have suggested that self-expanding stents may produce less vessel wall injury at initial deployment, leading to larger follow-up lumens than with balloon-expandable stents. However, the influence of the chronic stimulus from self-expanding stents on the vessel wall remains unknown. METHODS Sixty-two patients were randomly assigned to either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz balloon-expandable stent group (n = 30). Intravascular ultrasound was performed after stent deployment and at six-month follow-up. RESULTS At follow-up, the RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/- 1.7 mm(2) vs. 1.9 +/- 1.2 mm(2), p = 0.02) in the RADIUS group, no significant difference in net late lumen loss was observed between the two groups. On the other hand, analysis at the peristent margins demonstrated that mean late loss was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz group (0.1 +/- 2.1 mm(2) vs. 1.9 +/- 2.4 mm2, p = 0.02). CONCLUSIONS Serial volumetric IVUS revealed that the RADIUS stents continued to enlarge during the follow-up period. In this stent implantation protocol, this expansion was accompanied by a greater amount of neointima than the Palmaz-Schatz stents, resulting in similar late lumen loss in both configurations. In the peristent margins, however, late lumen loss was minimized with the RADIUS stents. (J Am Cell Cardiol 2001;37:1329-34) (C) 2001 by the American College of Cardiology. C1 Stanford Univ, Med Ctr, Ctr Res Cardiovasc Intervent, Stanford, CA 94305 USA. Cardiovasc Associates, Eugene, OR USA. Scripps Clin, La Jolla, CA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Piedmont Hosp, Atlanta, GA USA. Los Angeles Cardiol Associates, Los Angeles, CA USA. Moses Cone Mem Hosp, Greensboro, NC USA. Mayo Clin, Rochester, MN USA. Cooper Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fitzgerald, PJ (reprint author), Stanford Univ, Med Ctr, Ctr Res Cardiovasc Intervent, 300 Pasteur Dr,Room H3554, Stanford, CA 94305 USA. RI Honda, Yasuhiro/J-6227-2013 OI Honda, Yasuhiro/0000-0002-0102-7841 NR 28 TC 54 Z9 60 U1 0 U2 1 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 APR PY 2001 VL 37 IS 5 BP 1329 EP 1334 DI 10.1016/S0735-1097(01)01162-7 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 418PZ UT WOS:000167901700027 PM 11300443 ER PT J AU Albert, M Chung, LW Rosenbaum, C Brown, P AF Albert, M Chung, LW Rosenbaum, C Brown, P TI Relationship between medication use and cognitive decline in older persons. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P207 BP S78 EP S78 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300282 ER PT J AU Alessi, CA Kim, EC AF Alessi, CA Kim, EC TI Daytime sleepiness and functional status among nursing home residents. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P285 BP S102 EP S102 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300360 ER PT J AU Chodosh, J Shekelle, PG Ferrell, B Solomon, DH Roth, CP Saliba, D MacLean, CH Young, RT Wenger, NS AF Chodosh, J Shekelle, PG Ferrell, B Solomon, DH Roth, CP Saliba, D MacLean, CH Young, RT Wenger, NS TI Quality of care for chronic pain among vulnerable elders. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Gen Internal Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda GRECC, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Div Rheumatol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P430 BP S146 EP S146 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300504 ER PT J AU Conn, V Siddle, JU Guthrie, M Fox, AR AF Conn, V Siddle, JU Guthrie, M Fox, AR TI Decreasing emergency room utilization: A Home-Based Primary Care Quality Assurance Program. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P186 BP S72 EP S72 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300262 ER PT J AU Dhanani, S Yoh, E Harada, N Percy, L Makinodan, T AF Dhanani, S Yoh, E Harada, N Percy, L Makinodan, T TI Healthcare providers' understanding of herbal pharmacology. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 VA Greater Los Angeles HealthCare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P182 BP S71 EP S71 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300258 ER PT J AU Fidellow, RE Miles, TP Parchman, M AF Fidellow, RE Miles, TP Parchman, M TI Satisfaction with medical care among recently decreased patients in the 1993 Medicare Beneficiaries survey (MCBS). SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P357 BP S123 EP S124 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300431 ER PT J AU Fox, AR Turner, GH Granieri, EC AF Fox, AR Turner, GH Granieri, EC TI Evaluation of a first-year medical student program in geriatric medicine. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 GRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P271 BP S98 EP S98 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300346 ER PT J AU Ghajarnia, MM Mendez, MF AF Ghajarnia, MM Mendez, MF TI Posterior Cortical Atrophy versus early-onset Alzheimer's disease: Clinical and neuroimaging differences. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Dementia Clin, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA A8 BP S3 EP S3 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300040 ER PT J AU Granieri, EC Fox, AR Siddle, JU Young, A Coyne, J Courtright, L AF Granieri, EC Fox, AR Siddle, JU Young, A Coyne, J Courtright, L TI Educational needs assessment results from a regional didactic geriatrics program. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 GRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P150 BP S62 EP S62 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300227 ER PT J AU Kim, B Lyons, TM Parada, JP Uphold, CR Yarnold, PR Goetz, MB DeHovitz, JA Weinstein, RA Campo, RE Bennett, CL AF Kim, B Lyons, TM Parada, JP Uphold, CR Yarnold, PR Goetz, MB DeHovitz, JA Weinstein, RA Campo, RE Bennett, CL TI Hiv-related Pneumocystis carinii pneumonia in older patients hospitalized in 1995-1997. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Buehler Ctr Aging, Chicago, IL USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. VA Chicago Hlth Care Syst, Lakeside Div, Chicago, IL USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. Hines VA Hosp, Midwest Ctr Hlth Serv Res & Policy, Hines, IL USA. Malcolm Randall VA Med Ctr, Brain Rehab Res Ctr, Gainesville, FL USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. Rush Med Coll, Dept Med, Chicago, IL 60612 USA. Jackson Mem Hosp, Div Infect Dis & Special Immunol, Miami, FL USA. RI Bennett, Charles/C-2050-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P55 BP S32 EP S32 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300132 ER PT J AU Ly, JM Percy, L Dhanani, S AF Ly, JM Percy, L Dhanani, S TI The prevalence of herbal medcinal use in geriatric veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P295 BP S104 EP S105 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300369 ER PT J AU Wenger, NS Saliba, D Roth, C MacLean, C Young, RT Kamberg, C Shekelle, P Solomon, DH AF Wenger, NS Saliba, D Roth, C MacLean, C Young, RT Kamberg, C Shekelle, P Solomon, DH TI Quality of initial outpatient and inpatient evaluation for vulnerable elders. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Los Angeles VA Med Ctrs, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2001 VL 49 IS 4 MA P61 BP S34 EP S34 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 426CC UT WOS:000168331300138 ER PT J AU Marino, M Andrews, D Brown, D McCluskey, RT AF Marino, M Andrews, D Brown, D McCluskey, RT TI Transcytosis of retinol-binding protein across renal proximal tubule cells after megalin (gp 330)-mediated endocytosis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RECEPTOR-RELATED PROTEIN; GLYCOPROTEIN 330/MEGALIN; HEYMANN NEPHRITIS; MESSENGER-RNA; THYROID-CELLS; BLOOD-BRAIN; GENE FAMILY; GP330; KIDNEY; TRANSPORT AB Plasma retinol-binding protein (RBP) combined with vitamin A (retinol) is partially filtered through the glomerulus and then absorbed by proximal tubule cells, leading to recycling of retinol to the circulation. Recently, it was shown that reabsorption of RBP-retinol complexes by proximal tubule cells is mediated by megalin (gp 330), an apical endocytic receptor. It was proposed that REP is transported by megalin to lysosomes, where it is degraded, thus liberating retinol, which then combines with newly synthesized REP to be secreted into the bloodstream. This study shows that passage of REP through immortalized rat renal proximal tubule (IRPT) cells occurs by transcytosis after megalin-mediated endocytosis, which provides an alternative pathway for recycling of retinol. IRPT cells cultured as polarized monolayers with tight junctions were used on permeable filters in the upper chamber of dual-chambered devices, with megalin expression exclusively on the upper surface. After addition of REP to the upper chamber and incubation at 37 degreesC, intact REP was found in fluids that were collected from the lower chamber. In contrast, control substances (mannitol, lysozyme, albumin, and glutathione-S-transferase) were not appreciably transported across IRPT cells, indicating that passage of REP was by transcytosis and not by paracellular leakage. Confocal microscopy analysis of IRPT cells after addition of REP to the upper chamber revealed RBP-containing granules at the apical membrane, subapically, and also at basolateral membranes. When REP was added to IRPT cells together with megalin competitors, the amount of transcytosed REP was markedly reduced. We also found that some REP was internalized and degraded by IRPT cells, but this process was not appreciably affected by megalin competitors, indicating that REP endocytosed by megalin was not transported to lysosomes and degraded but rather transcytosed across IRPT cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Res Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA USA. RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. FU NIDDK NIH HHS [DK42956, DK46301] NR 34 TC 50 Z9 51 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2001 VL 12 IS 4 BP 637 EP 648 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 417JY UT WOS:000167832900005 PM 11274224 ER PT J AU Jaklitsch, MT Mery, CM Lukanich, JM Richards, WG Bueno, R Swanson, SJ Mentzer, SJ Davis, BD Allred, EN Sugarbaker, DJ AF Jaklitsch, MT Mery, CM Lukanich, JM Richards, WG Bueno, R Swanson, SJ Mentzer, SJ Davis, BD Allred, EN Sugarbaker, DJ TI Sequential thoracic metastasectomy prolongs survival by re-establishing local control within the chest SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 25th Annual meeting of the Western-Thoracic-Surgical-Association CY JUN 23-26, 1999 CL LAKE TAHOE, CALIFORNIA SP Western Thorac Surg Assoc ID PULMONARY METASTASES; SURGICAL-TREATMENT; LUNG METASTASES; SOFT-TISSUE; RESECTION; SURGERY AB Objective: The value of sequential thoracic metastasectomies is unknown. We evaluate repeat metastasectomy for limited recurrences within the thorax. Methods: From July 1988 to September 1998, 54 patients underwent 2 to 6 separate sequential procedures to excise metastases after recurrence isolated to the thorax. Kaplan-Meier survival and Cox modeling determined prognostic variables. Results: Thirty-three men and 21 women, 22 to 76 years underwent 2 (100%, n = 54), 3 (50%), 4 (22%), or 5 to 6 (11%) metastasectomies. Fifty-four percent of patients had carcinoma, 35% sarcoma, 9% germ cell, and 2% melanoma. There were no operative deaths; all late deaths occurred from cancer. Median follow-up was 48 months. Cumulative 5-year survival from the second procedure was 57%. After the second, third, fourth, and fifth procedures, respectively, permanent control was achieved in 15 (27%) of 54 patients, 5 (19%) of 27, 1 (8%) of 12, and 0 of 7. Recurrence amenable to additional surgery occurred in 27 (50%) of 54, 12 (44%) of 27, 6 (50%) of 12, and 1 (17%) of 6. Mean hazard fur the development of unresectable recurrence increased from 0.21 after the second procedure to 0.91 after the fifth procedure, The 5-year survival for the 27 patients undergoing only 3 metastasectomies was 60% (median not yet reached), 33% for the 15 patients undergoing only 3 metastasectomies (median 34.7 months), and 38% for the 12 patients undergoing 4 or more (median 45.6 months). From the time a recurrence was declared unresectable, patients had a 19% 2-year survival (median 8 months). Conclusions: Multiple attempts to re-establish intrathoracic control of metastatic disease is justified in carefully selected patients, but the magnitude of benefit decays with each subsequent attempt. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Publ Hlth, Dept Neurol, Boston, MA 02115 USA. RP Jaklitsch, MT (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. NR 20 TC 53 Z9 53 U1 0 U2 0 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 APR PY 2001 VL 121 IS 4 BP 657 EP 667 DI 10.1067/mtc.2001.112822 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 421XB UT WOS:000168087900006 PM 11279405 ER PT J AU Fiore, LD Scola, MA Cantillon, CE Brophy, MT AF Fiore, LD Scola, MA Cantillon, CE Brophy, MT TI Anaphylactoid reactions to vitamin K SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE anaphylaxis; vitamin K; anticoagulants ID ACUTE CARDIOVASCULAR COLLAPSE; ADVERSE SKIN REACTION; PHYTONADIONE; HYPERSENSITIVITY; INJECTION; SHOCK AB Anaphylactoid reactions in patients receiving intravenously administered vitamin K have been reported in the literature. To summarize the known data on anaphylactoid reactions from administration of vitamin K, we reviewed all published and unpublished reports of this adverse reaction. Published reports were obtained through medline (1966-1999) and EMBASE (1971-1999) searches of the English language literature and review of references from identified case reports. Unpublished reports were obtained using the Spontaneous Reporting System Adverse Reaction database of the United States Food and Drug Administration (FDA) between August 1968 and September 1997. All adverse drug reactions to vitamin K were categorized by route of drug administration, dose and standard adverse reaction code. In the FDA reports, we defined anaphylactoid reactions as any adverse drug reaction coded as either anaphylaxis, allergic reaction, apnea, dyspnea, death, heart arrest, hypotension, shock or vasodilatation. Additionally, all fatal and life-threatening FDA reported reactions were reviewed to determine if they could represent an anaphylactoid reaction missed by the above definition. The literature review uncovered a total of 23 cases (3 fatal) of anaphylactoid reactions from intravenous vitamin K. The FDA database contained a total of 2236 adverse drug reactions reported in 1019 patients receiving vitamin K by all routes of administration. Of the 192 patients with reactions reported for intravenous vitamin K, 132 patients (69 %) had a reaction defined as anaphylactoid, with 24 fatalities (18 %) attributed to the vitamin K reaction. There were 21 patients with anaphylactoid reactions and 4 fatalities reported with doses of intravenous vitamin K of less than 5 mgs. For the 217 patients with reactions reported due to vitamin K via a non-intravenous route of administration, 38 patients had reactions meeting the definition of anaphylactoid (18 %), with 1 fatality (3 %) attributed to the drug. The absolute risk of an anaphylactoid reaction to intravenous vitamin K cannot be determined by this study, but the relatively small number of documented cases despite widespread use of this drug suggest that the reaction is rare. Anaphylactic reactions and case fatality reports were found even when intravenous vitamin K was given at low doses by slow dilute infusion. The pathogenesis of this reaction is unknown and may be multifactorial with etiologies including vasodilation induced by the solubilizing vehicle or immune-mediated processes. We conclude that use of intravenous vitamin K should be limited to patients with serious hemorrhage due to a coagulopathy that is secondary to a relative or absolute deficiency of vitamin K. C1 VA Boston Healthcare Syst, MAVERIC, MAV 151, Boston, MA 02130 USA. RP Brophy, MT (reprint author), VA Boston Healthcare Syst, MAVERIC, MAV 151, 150 S Huntington Ave, Boston, MA 02130 USA. NR 29 TC 52 Z9 56 U1 1 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 2001 VL 11 IS 2 BP 175 EP 183 DI 10.1023/A:1011237019082 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 443DM UT WOS:000169325200011 PM 11406734 ER PT J AU Kolchinsky, P Kiprilov, E Bartley, P Rubinstein, R Sodroski, J AF Kolchinsky, P Kiprilov, E Bartley, P Rubinstein, R Sodroski, J TI Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN GP120; SOLUBLE CD4 BINDING; T-LYMPHOTROPIC RETROVIRUS; HIV-1 ENTRY; CONFORMATIONAL-CHANGES; CHEMOKINE RECEPTORS; AIDS VIRUS; SYNCYTIUM FORMATION; HTLV-III; V3 LOOP AB The gp120 envelope glycoprotein of primary human immunodeficiency virus type 1 (HIV-1) promotes virus entry by sequentially binding CD4 and the CCR5 chemokine receptor on the target cell. Previously, we adapted a primary HIV-1 isolate, ADA, to replicate in CD4-negative canine cells expressing human CCR5. The gp120 changes responsible for CD4-independent replication were limited to the V2 loop-V1/V2 stem. Here we show that elimination of a single glycosylation site at asparagine 197 in the V1/V2 stem is sufficient for CD4-independent gp120 binding to CCR5 and for HIV-1 entry into CD4-negative cells expressing CCR5. Deletion of the V1/V2 loops also allowed CD4-independent viral entry and gp120 binding to CCR5. The binding of the wild-type ADA gp120 to CCR5 was less dependent upon CD4 at 4 degreesC than at 37 degreesC. In the absence of the V1/V2 loops, neither removal of the N-linked carbohydrate at asparagine 197 nor lowering of the temperature increased the CD4-independent phenotypes, A CCR5-binding conformation of gp120, achieved by CD4 interaction or by modification of temperature, glycosylation, or variable loops, was preferentially recognized by the monoclonal antibody 48d. These results suggest that the CCR5-binding region of gp120 is occluded by the V1/V2 variable loops, the position of which can be modulated by temperature, CD4 binding, or an N-linked glycan in the V1/V2 stem. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,FB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI24755, AI28691, AI41851, P30 AI028691, R01 AI041851, R37 AI024755] NR 82 TC 141 Z9 143 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2001 VL 75 IS 7 BP 3435 EP 3443 DI 10.1128/JVI.75.7.3435-3443.2001 PG 9 WC Virology SC Virology GA 410YX UT WOS:000167469600038 PM 11238869 ER PT J AU Covinsky, KE Kahana, E Kahana, B Kercher, K Schumacher, JG Justice, AC AF Covinsky, KE Kahana, E Kahana, B Kercher, K Schumacher, JG Justice, AC TI History and mobility exam index to identify community-dwelling elderly persons at risk of falling SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID OLDER PERSONS; INJURIOUS FALLS; HEALTH-STATUS; NURSING-HOME; ADULTS; POPULATION; MORTALITY; SYMPTOMS; OUTCOMES; BALANCE AB Background. Falls are common in community-dwelling elderly persons and are a frequent source of morbidity. Simple indices to prospectively stratify people into categories at different fall-risk would be useful to health care practitioners. Our goal was to develop a fall-risk index that discriminated between people at high and low risk of falling. Methods. We evaluated the risk of falling over a one-year period in 557 elderly persons (mean age 81.6) living in a retirement community. On the baseline interview, we asked subjects if they had fallen in the previous year and evaluated risk factors in six additional conceptual categories. On the follow-up interview. one year later, we again asked subjects if they had fallen in the prior year. We evaluated risk factors in the different conceptual categories and used logistic regression to determine: the independent predictors of falling over a one-year period. We used these independent predictors to create a fall-risk index. We compared the ability of a prior falls history with other risk factors and with the combination of a falls history and other risk factors to discriminate fallers from nonfallers. Results. A fall in the previous year (OR = 2.42, 95% Cl = 1.49-3.93). a symptom of either balance difficulty or dirtiness (OR = 1.83. 95% CI = 1.16-2.89). or an abnormal mobility exam (OR = 2.61. 95% CI = 1.64-4.26) were independent predictors of falling over the subsequent year. These three risk factors together (L statistic = .71) discriminated fallers from nonfallers better than previous history of falls alone (e statistic = .61) or the symptomatic and exam risk factors alone ( statistic = .68). When combined into a risk index, the three independent risk factors stratify people into groups whose risk for falling over the subsequent year ranges from 10% to 51%. Conclusion, A history of falling over the prior year, a risk factor that can be obtained from a clinical history (balance difficulty or dizziness), and a risk factor that can be obtained from a physical exam (mobility difficulty) stratify people into groups at low and high risk of falling over the subsequent year. This risk index may provide a simple method of assessing fall risk in community-dwelling elderly persons. However, it requires validation in other subjects before it can be recommended for widespread use. C1 San Francisco VAMC 111G, Div Geriatr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Case Western Reserve Univ, Dept Sociol, Cleveland, OH 44106 USA. Cleveland State Univ, Dept Psychol, Cleveland, OH 44115 USA. Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Covinsky, KE (reprint author), San Francisco VAMC 111G, Div Geriatr, 4150 Clement, San Francisco, CA 94121 USA. FU NIA NIH HHS [K23AG00714, AG-10738, AG-07823] NR 43 TC 39 Z9 39 U1 1 U2 5 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2001 VL 56 IS 4 BP M253 EP M259 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 421AZ UT WOS:000168041100016 PM 11283200 ER PT J AU Lansang, MC Price, DA Laffel, LMB Osei, SY Fisher, NDL Erani, D Hollenberg, NK AF Lansang, MC Price, DA Laffel, LMB Osei, SY Fisher, NDL Erani, D Hollenberg, NK TI Renal vascular responses to captopril and to candesartan in patients with type 1 diabetes mellitus SO KIDNEY INTERNATIONAL LA English DT Article DE ACE inhibition; renin-angiotensin system; AT(1) receptor blocker; renal plasma flow; hemodynamics; vascular tone ID RENIN-ANGIOTENSIN SYSTEM; CONVERTING ENZYME-INHIBITION; HUMAN PERIPHERAL PLASMA; II RECEPTOR BLOCKADE; NEPHROPATHY; GLOMERULOPATHY; HYPERGLYCEMIA; HYPERTENSION; MICROALBUMINURIA; PATHOGENESIS AB Background Enhanced renal vasodilator responses to angiotensin-converting enzyme (ACE) inhibition in diabetes mellitus despite a normal or low plasma renin activity level have suggested intrarenal activation of the renin-angiotensin system in this disease. There is, however, a continuing debate as to the mediators of the renal hemodynamic response to ACE inhibition-reduced angiotensin IT formation or pathways involving kinins, prostaglandins, and nitric oxide. Methods. Twelve patients with type 1 diabetes mellitus of 18 +/- 3.2 (SEM) years of duration (7 females and 5 males, ages 17 to 50, 32 +/- 4.0 years) who were free of sustained microalbuminuria and on a high-salt diet were given the ACE inhibitor captopril (25 mg orally) on one day and the AT(1) receptor blocker candesartan (16 mg orally) on another day. Renal plasma flow (RPF) and glomerular filtration rate were measured before and for four hours after administration. Results. Both drugs caused a significant increase in RPF (captopril 574 +/- 26 to 625 +/- 37 mL/min/1.73 m(2), P = 0.008, candesartan 577 +/- 26 to 643 +/- 37, P = 0.004). There was a highly significant correlation between the responses to captopril and to candesartan (r = 0.86, P < 0.001). Seven subjects had an RPF response to captopril that was accentuated (90 13 mL/min/1.73 m(2)), while five had a response that was normal (-4 +/- 9). There was no significant change in glomerular filtration rate on either drug. Conclusion. The remarkable rise in RPF in response to captopril and candesartan despite high-salt balance suggests the intrarenal activation of the renin-angiotensin system in diabetes that is not reflected in plasma renin levels. The high correlation between the renal hemodynamic response to captopril and to candesartan indicates that reduced angiotensin fl formation is the main mechanism of action of the ACE inhibitor. C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hollenberg, NK (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, 75 Francis St, Boston, MA 02115 USA. FU NCRR NIH HHS [M01RR026376]; NHLBI NIH HHS [T32 HL-07609]; NIDDK NIH HHS [1 R01 DK54668-01]; PHS HHS [1P50 ML 53000-01, P01AC00059916] NR 33 TC 39 Z9 39 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2001 VL 59 IS 4 BP 1432 EP 1438 DI 10.1046/j.1523-1755.2001.0590041432.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 415RV UT WOS:000167737200025 PM 11260405 ER PT J AU Xu, L Tan, LJ Goldring, MB Olsen, BR Li, YF AF Xu, L Tan, LJ Goldring, MB Olsen, BR Li, YF TI Expression of frizzled genes in mouse costochondral chondrocytes SO MATRIX BIOLOGY LA English DT Article ID DROSOPHILA; RECEPTOR; POLARITY; WINGLESS; PROTEIN; ENCODES; FAMILY AB Protein products of frizzled genes are cell membrane receptors for Wnt proteins that play multiple roles during development. We examined the expression of nine frizzled genes in mouse chondrocytes, and detected transcripts of six of the nine genes. We also cloned the entire cDNA of mouse frizzled-l and compared its cDNA sequence and the cysteine-rich and transmembrane domains of its translated product to sequences of frizzled-l from C. elegans, Drosophila, chicken and human. We used the T31 Mouse/Hamster radiation hybrid panel to map the mouse frizzled-l to mouse chromosome 5 (5 cM from the centromere), and frizzled-9 to mouse chromosome 5 (74 cM from the centromere). (C) 2001 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved. C1 Harvard Univ, Sch Dent Med, Dept Growth & Dev, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Rheumatol, Boston, MA 02115 USA. Harvard Univ, Inst Med, New England Baptist Bone & Joint Inst, Boston, MA 02115 USA. Harvard Univ, Forsyth Dept Oral Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Li, YF (reprint author), Harvard Univ, Sch Dent Med, Dept Growth & Dev, 188 Longwood Ave, Boston, MA 02115 USA. FU NIAMS NIH HHS [R03 AR 45823, R01 AR 36819, R01 AR 45378] NR 14 TC 9 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD APR PY 2001 VL 20 IS 2 BP 147 EP 151 DI 10.1016/S0945-053X(00)00138-4 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 435EC UT WOS:000168863600008 PM 11334716 ER PT J AU Justice, AC Chang, CH Rabeneck, L Zackin, R AF Justice, AC Chang, CH Rabeneck, L Zackin, R TI Clinical importance of provider-reported HIV symptoms compared with patient-report SO MEDICAL CARE LA English DT Article DE symptoms; provider report; self report; health related quality of life; adverse drug reactions ID QUALITY-OF-LIFE; FUNCTIONAL STATUS; CUBIC MILLIMETER; INFECTED ADULTS; RELIABILITY; VALIDITY; PHYSICIANS; PREVALENCE; PREDICTORS; DISEASE AB BACKGROUND. Although the patient experiences the symptoms, only symptoms that providers recognize and report "count" in most clinical and research settings. Reliance upon provider-report has been justified by the claim that providers report only "clinically important" symptoms. OBJECTIVE. TO determine whether provider reported symptoms constitute a more "clinically important subset of patient-reported symptoms in HIV infection. DESIGN. Secondary analyses of AIDS Clinical Trials 175 (ACTG 175), a randomized controlled trial of combination antiviral therapy among patients with moderate HIV disease. SETTING. Large, multicenter study. PATIENTS. 1,262 patients who participated in the health-related quality of life (HRQOL) sub-study and for whom providers completed symptom forms. MEASUREMENTS. Patient- and provider-reported symptoms, HRQOL, risk of recent hospitalization, survival, CD4 cell count, and plasma HIV-1 RNA levels. RESULTS. On average, providers reported 3-fold fewer symptoms than patients did, but the degree of under report varied by symp-tom. When patient-reports were used as a gold standard, provider-reports demonstrated poor sensitivity (mean 0.25) and good specificity (mean 0.96). Agreement beyond chance was fair (mean kappa 0.35) and did not improve when weighted by symptom severity. Site specific variation was greater for provider than for patient-reported symptoms (R-2: 0.15 and 0.05 respectively). Patient-reported symptoms were substantially more strongly associated with the physical health scale and all HRQOL subscales than provider-reported symptoms (P < 0.0001). Patient-reported symptoms were equally strongly associated with survival (P > 0.50) and recent hospitalization as provider-reported symptoms (P > 0.48). Of note, patient-reported symptoms were independently associated with survival and recent hospitalization after adjustment for CD4 cell count and plasma HIV-1 RNA levels (P < 0.05). CONCLUSIONS. Provider-reported symptoms are not a more clinically important subset of patient-reported symptoms. Patient-reported symptom checklists are likely to be more complete and more strongly associated with HRQOL. Further, patient-reported symptoms are as related to recent hospitalization and survival as provider-reported symptoms. An HIV specific, patient-completed symptom checklist might substantially improve symptom reporting for adverse drug event monitoring, clinical management and medical research. C1 VA Pittsburgh Healthcare Syst, Sect GIM, Ctr Res Hlth Care, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Gen Internal Med Sect, Pittsburgh, PA USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Ctr Excellence, Dept Vet Affairs Hlth Serv Res & Dev, Houston, TX 77030 USA. Harvard Univ, Stat & Data Anal Ctr, Boston, MA 02115 USA. RP Justice, AC (reprint author), VA Pittsburgh Healthcare Syst, Sect GIM, Ctr Res Hlth Care, 11E124,Univ Dr C, Pittsburgh, PA 15240 USA. FU NIA NIH HHS [K23 AG 00826-03]; NIAMS NIH HHS [U01 AR38855, U01 AR38858] NR 25 TC 68 Z9 69 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2001 VL 39 IS 4 BP 397 EP 408 DI 10.1097/00005650-200104000-00010 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 419RD UT WOS:000167961700010 PM 11329526 ER PT J AU Hamoen, KE Rinkes, IHMB Morgan, JR AF Hamoen, KE Rinkes, IHMB Morgan, JR TI Hepatocyte growth factor and melanoma: gene transfer studies in human melanocytes SO MELANOMA RESEARCH LA English DT Article DE growth factor; melanocyte; retrovirus gene transfer ID FACTOR SCATTER FACTOR; C-MET; ACTIVATION; CELLS; TRANSFORMATION; PHENOTYPE; RECEPTOR; IDENTIFICATION; PURIFICATION; EXPRESSION AB Hepatocyte growth factor (HGF), a fibroblast-derived protein that affects the growth, motility and differentiation of epithelial cells, is a mitogen for human melanocytes and has recently been implicated as an important factor for the development and dissemination of melanomas. To better define the possible role of HGF in the multi-step progression from melanocyte to melanoma cell, we used retrovirus-mediated gene transfer to introduce the gene encoding human HGF into normal human melanocytes, thus causing these cells to produce a growth factor they do not normally express and creating a new autocrine loop as sometimes occurs in melanoma cells. Cells were transduced with an efficiency of 6%, and the modified cells synthesized and secreted significant levels of HGF (6.6 ng/10(7) cells per 24 h) in vitro. Cells expressing HGF had a higher rate of proliferation when compared with unmodified cells and formed large, dense, melanin-positive colonies on a plastic surface. Immunostaining showed HGF-positive melanocytes with varying levels of expression, and HGF protein was detected throughout the whole cell. Although proliferation of HGF-expressing melanocytes was enhanced, they failed to form colonies in a soft agar assay. These results suggest that expression of HGF, by virtue of its ability to enhance proliferation and cell clustering, may play a role in the multi-step process of transformation, but an autocrine signal of HGF alone is not sufficient for malignant transformation. (C) 2001 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Hosp Children, Boston, MA 02114 USA. Utrecht Med Ctr, Dept Surg, Utrecht, Netherlands. RP Morgan, JR (reprint author), Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, 51 Blossom St, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [HD-28528] NR 28 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD APR PY 2001 VL 11 IS 2 BP 89 EP 97 DI 10.1097/00008390-200104000-00002 PG 9 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 423UM UT WOS:000168196200002 PM 11333132 ER PT J AU Murray, EJB Beamer, WG Duarte, ME Behnam, K Grisanti, MS Murray, SS AF Murray, EJB Beamer, WG Duarte, ME Behnam, K Grisanti, MS Murray, SS TI Effects of dietary restriction on appendicular bone in the SENCAR mouse SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 10-14, 1997 CL CINCINNATI, OHIO SP Amer Soc Bone & Mineral Res ID PROTEIN-KINASE-C; SKIN TUMOR PROMOTION; HIGH-FAT DIETS; EPIDERMAL HYPERPLASIA; ENERGY RESTRICTION; ALTERED EXPRESSION; OXIDATIVE EVENTS; CALCIUM-REPLETE; GENE-EXPRESSION; B6C3F1 MICE AB Peptide hormones, cytokines, and growth factors regulate cellular metabolism by stimulating second messenger signal transduction cascades in target tissues. A mutation in the regulatory domain of protein kinase C (PKC) in SENCAR (sensitive to carcinogenesis) mice renders them extremely sensitive to diacylglycerol and phorbol esters, resulting in rapid growth, high free radical generation, carcinogenesis, and metabolic bone disease. Dietary restriction (DR) normalizes PKC and ameliorates adverse downstream effects, including carcinogenesis, in SENCAR mice. We hypothesized that DR sufficient to ameliorate carcinogenesis would prevent or delay the early onset of metabolic bone disease in SENCAR mice. Male mice were assigned to 1 of 4 feeding groups from 10 to 16 weeks of age [the critical period when metabolic bone disease develops): ad libitum (AL)-fed; AL antioxidant (0.07% thioproline)-fed; 40% DR; or 40% DR antioxidant-fed. Femoral bone mass was determined gravimetrically. Tibial total, cortical, and trabecular bone mineral density (BMD) were determined by quantitative computed tomography. Body weight, femoral bone mass, and tibial cortical BMD were lower in DR than in AL mice. However, tibial total and trabecular BMD were higher in DR than in AL mice. Serum calcitonin, the hormone that inhibits the osteoclastic bone resorption that is most notable in trabecular bone, was 2-fold higher in DR than in AL-fed mice. Dietary thioproline had no major effects. Thus, DR sufficient to ameliorate carcinogenesis in SENCAR mice did not prevent early-onset metabolic bone disease, but it had a beneficial effect on tibial trabecular BMD that occurred at the apparent expense of cortical BMD. DR in SENCAR mice was also associated with elevated serum calcitonin, which may inhibit osteoclastic resorption and account for trabecular bone conservation in this model. In conclusion, PKC or the downstream metabolic processes regulated by it appear to play previously unrecognized roles in the regulation of tibial trabecular BMD and serum calcitonin in SENCAR mice. Copyright (C) 2001 by W.B. Saunders Company. C1 VA Greater Los Angeles Healthcare Syst, GRECC, Sepulveda Ambulatory Care Ctr & Nursing Home, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Jackson Lab, Bar Harbor, ME 04609 USA. Univ Fed Fluminense, Dept Patol, Rio De Janeiro, Brazil. RP Murray, EJB (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC, Sepulveda Ambulatory Care Ctr & Nursing Home, 11-E,16111 Plummer St, Sepulveda, CA 91343 USA. NR 40 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2001 VL 50 IS 4 BP 436 EP 442 DI 10.1053/meta.2001.21694 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 418YV UT WOS:000167923400011 ER PT J AU Ernst, P Wang, J Huang, M Goodman, RH Korsmeyer, SJ AF Ernst, P Wang, J Huang, M Goodman, RH Korsmeyer, SJ TI MLL and CREB bind cooperatively to the nuclear coactivator CREB-binding protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC-CELLS CAUSES; VIRUS TYPE-1 TAX; TRANSCRIPTIONAL ACTIVITY; PHOSPHORYLATED CREB; DROSOPHILA-TRITHORAX; MAMMALIAN TRITHORAX; SECONDARY STRUCTURE; MUTANT MICE; KIX DOMAIN AB A fragment of the mixed-lineage leukemia (MLL) gene (MII, HRX,ALL-1) was identified in a yeast genetic screen designed to isolate proteins that interact with the CREB-CREB-binding protein (CBP) complex When tested for binding to CREB or CBP individually, this MLL fragment interacted directly with CBP, but not with CREB. In vitro binding experiments refined the minimal region of interaction to amino acids 2829 to 2883 of MLL, a potent transcriptional activation domain, and amino acids 581 to 687 of CBP (the CREB-binding or KIX domain). The transactivation activity of MLL was dependent on CBP, as either adenovirus E1A expression, which inhibits CBP activity, or alteration of MLL residues important for CBP interaction proved effective at inhibiting MLL mediated transactivation. Single amino acid substitutions within the MLL activation domain revealed that five hydrophobic residues, potentially forming a hydrophobic face of an amphipathic helix, were critical for the interaction of MLL with CBP. Using purified components, we found that the MLL activation domain facilitated the binding of CBP to phosphorylated CREB. In contrast with paradigms in which factors compete for limiting quantities of CBP, these results reveal that two distinct transcription factor activation domains can cooperatively target the same moth on CBP. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Med, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol, 1 Jimmy Fund Way,SM-758, Boston, MA 02115 USA. NR 63 TC 144 Z9 145 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2001 VL 21 IS 7 BP 2249 EP 2258 DI 10.1128/MCB.21.7.2249-2258.2001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 410QW UT WOS:000167451500001 PM 11259575 ER PT J AU Valverde, AM Mur, C Pons, S Alvarez, AM White, MF Kahn, CR Benito, M AF Valverde, AM Mur, C Pons, S Alvarez, AM White, MF Kahn, CR Benito, M TI Association of insulin receptor substrate 1 (IRS-1) y895 with grb-2 mediates the insulin signaling involved in IRS-1-deficient brown adipocyte mitogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR-I; ACTIVATED PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOTYROSINE PROTEIN; GLUCOSE-HOMEOSTASIS; GENE-EXPRESSION; MICE; SHC; CELLS; PHOSPHORYLATION AB We have recently generated immortalized fetal bro,vn adipocyte cell lines from insulin receptor substrate 1 (IRS-1) knockout mice and demonstrated an impairment in insulin-induced lipid synthesis as compared to wild-type cell lines. In this study, we investigated the consequences of IRS-1 deficiency on mitogenesis in response to insulin. The lack of IRS-1 resulted in the inability of insulin-stimulated IRS-1-deficient brown adipocytes to increase DNA synthesis and enter into SIG,IM phases of the cell cycle. These cells showed a severe impairment in activating mitogen-activated protein kinase kinase (MEK1/2) and p42-p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. IRS-1-deficient cells also lacked tyrosine phosphorylation of SHC and showed no SHC-Grb-2 association in response to insulin. The mitogenic response to insulin could be partially restored by enhancing IRS-2 tyrosine phosphorylation and its association with Grb-2 by inhibition of phosphatidylinositol 3-kinase activity through a feedback mechanism. Reconstitution of IRS-1-deficient brown adipocytes with wild-type IRS-1 restored insulin-induced IRS-1 and SHC tyrosine phosphorylation and IRS-1-Grb-2, IRS-1-SHC, and SHC-Grb-2 associations, leading to the activation of MAPK and enhancement of DNA synthesis. Reconstitution of IRS-1-deficient brown adipocytes with the IRS-1 mutant Tyr895Phe, which lacks IRS-1-Grb-2 binding, restored SCH-IRS-1 association and SHC-Grb-2 association. However, the lack of IRS-1-Grb-2 association impaired MAPK activation and DNA synthesis in insulin-stimulated mutant cells. These data provide strong evidence for an essential role of IRS-1 and its direct association with Grb-2 in the insulin signaling pathway leading to MARK activation and mitogenesis in brown adipocytes. C1 Univ Complutense Madrid, CSIC, Dept Bioquim & Biol Mol, Fac Farm, E-28040 Madrid, Spain. Univ Complutense, Ctr Citometria Flujo & Microscopia Confocal, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Benito, M (reprint author), Univ Complutense Madrid, CSIC, Dept Bioquim & Biol Mol, Fac Farm, Ciudad Univ, E-28040 Madrid, Spain. RI Pons , Sebastian/K-7794-2014 OI Pons , Sebastian/0000-0003-1027-0621 NR 37 TC 24 Z9 25 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2001 VL 21 IS 7 BP 2269 EP 2280 DI 10.1128/MCB.21.7.2269-2280.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 410QW UT WOS:000167451500003 PM 11259577 ER PT J AU Choi, DY Toledo-Aral, JJ Segal, R Halegoua, S AF Choi, DY Toledo-Aral, JJ Segal, R Halegoua, S TI Sustained signaling by phospholipase C-gamma mediates nerve growth factor-triggered gene expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FACTOR-INDUCED DIFFERENTIATION; PROTEIN-KINASE-C; PC12 CELLS; MESSENGER-RNA; TYROSINE PHOSPHORYLATION; TRANSDUCTION PATHWAYS; NEUROTROPHIC FACTORS; SELECTIVE INHIBITOR; MAP KINASES; VGF GENE AB In contrast to conventional signaling by growth factors that requires their continual presence, a 1-min pulse of nerve growth factor (NGF) is sufficient to induce electrical excitability in PC12 cells due to induction of the peripheral nerve type 1 (PN1) sodium channel gene. We have investigated the mechanism for this triggered signaling pathway by NGF in PC12 cells. Mutation of TrkA at key autophosphorylation sites indicates an essential role for the phospholipase C-gamma (PLC-gamma) binding site, but not the Shc binding site, for NGF-triggered induction of PN1, In concordance with results with Trk mutants, drug-mediated inhibition of PLC-gamma activity also blocks PN1 induction by NGF, Examination of the kinetics of TrkA autophosphorylation indicates that triggered signaling does not result from sustained activation and autophosphorylation of the TrkA receptor kinase, whose phosphorylation state declines rapidly after NGF removal. Rather, TrkA triggers an unexpectedly prolonged phosphorylation and activation of PLC-gamma signaling that is sustained for up to 2 h, Prevention of the elevation of intracellular Ca2+ levels using BAPTA-AM results in a block of PN1 induction by NGF. Sustained signaling by PLC-gamma provides a means for differential neuronal gene induction after transient exposure to NGF. C1 SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Halegoua, S (reprint author), SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. RI Toledo-Aral, Juan/F-2613-2015; IBIS, TERAPIA CELULA/P-3297-2015 OI Toledo-Aral, Juan/0000-0001-7512-7135; FU NINDS NIH HHS [NS18218, NS 35148, R01 NS018218] NR 51 TC 35 Z9 35 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2001 VL 21 IS 8 BP 2695 EP 2705 DI 10.1128/MCB.21.8.2695-2705.2001 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 416BN UT WOS:000167760000008 PM 11283249 ER PT J AU Hu, B Mitra, J van den Heuvel, S Enders, GH AF Hu, B Mitra, J van den Heuvel, S Enders, GH TI S and G(2) phase roles for Cdk2 revealed by inducible expression of a dominant-negative mutant in human cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CYCLIN-DEPENDENT KINASE-2; DNA-DAMAGE CHECKPOINT; XENOPUS EGG EXTRACTS; PROTEIN-KINASE; MAMMALIAN-CELLS; CENTROSOME DUPLICATION; RETINOBLASTOMA PROTEIN; REPLICATION CHECKPOINT; CATALYTIC SUBUNIT; CRYSTAL-STRUCTURE AB Cyclin-dependent kinase 2 (Cdk2) is essential for initiation of DNA synthesis in higher eukaryotes, Biochemical studies in Xenopus egg extracts and microinjection studies in human cells have suggested an additional function for Cdk2 in activation of Cdk1 and entry into mitosis, To further examine the role of Cdk2 in human cells, we generated stable clones with inducible expression of wild-type and dominant-negative forms of the enzyme (Cdk2-wt and Cdk2-dn, respectively). Both exogenous proteins associated efficiently with endogenous cyclins, Cdk2-wt had no apparent effect on the cell division cycle, whereas Cdk2-dn inhibited progression through several distinct stages, Cdk2-dn induction could arrest cells at the G(1)/S transition, as previously observed in transient expression studies. However, under normal culture conditions, Cdk2-dn induction primarily arrested cells with S and G(2)/M DNA contents. Several observations suggested that the latter cells were in G(2) phase, prior to the onset of mitosis: these cells contained uncondensed chromosomes, low levels of cyclin B-associated kinase activity, and high levels of tyrosine-phosphorylated Cdk1, Furthermore, Cdk2-dn did not delay progression through mitosis upon release of cells from a nocodazole block, Although the G(2) arrest imposed by Cdk2-dn was similar to that imposed by the DNA damage checkpoint, the former was distinguished by its resistance to caffeine. These findings provide evidence for essential functions of Cdk2 during S and G(2) phases of the mammalian cell cycle. C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Enders, GH (reprint author), Penn GI Div, 600 CRB,415 Curie Blvd, Philadelphia, PA 19104 USA. RI van den Heuvel, Sander/B-8892-2011 FU NIDDK NIH HHS [P30 DK50306, P30 DK050306] NR 81 TC 98 Z9 101 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2001 VL 21 IS 8 BP 2755 EP 2766 DI 10.1128/MCB.21.8.2755-2766.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 416BN UT WOS:000167760000014 PM 11283255 ER PT J AU Angeloni, D Duh, FM Wei, MH Johnson, BE Lerman, MI AF Angeloni, D Duh, FM Wei, MH Johnson, BE Lerman, MI TI A C-to-A single nucleotide polymorphism in intron 2 of the human CACNA2D2 gene that maps at 3p21.3 SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE CACNA2D2; loss of heterozygosity (LOH); lung cancer; single nucleotide polymorphism (SNP) C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Angeloni, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 3 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD APR PY 2001 VL 15 IS 2 BP 125 EP 127 DI 10.1006/mcpr.2000.0341 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 422AL UT WOS:000168095700010 PM 11292331 ER PT J AU Pennaneach, V Salles-Passador, I Munshi, A Brickner, H Regazzoni, K Dick, F Dyson, N Chen, TT Wang, JYJ Fotedar, R Fotedar, A AF Pennaneach, V Salles-Passador, I Munshi, A Brickner, H Regazzoni, K Dick, F Dyson, N Chen, TT Wang, JYJ Fotedar, R Fotedar, A TI The large subunit of replication factor C promotes cell survival after DNA damage in an LxCxE motif- and Rb-dependent manner SO MOLECULAR CELL LA English DT Article ID S-PHASE ENTRY; RETINOBLASTOMA PROTEIN; CYCLE ARREST; SACCHAROMYCES-CEREVISIAE; P53 FUNCTION; T-ANTIGEN; BINDING; COMPLEX; APOPTOSIS; KINASE AB Retinoblastoma (Rb) protein promotes cell survival after DNA damage. We show here that the LxCxE binding site in Rb mediates both cell survival and cell-cycle arrest after DNA damage. Replication factor C (RF-C) complex plays an important role in DNA replication. We describe a novel function of the large subunit of RF-C in promoting cell survival after DNA damage. RF-Cp145 contains an LxCxE motif, and mutation of this motif abolishes the protective effect of RF-Cp145. The inability of wild-type RF-Cp145 to promote cell survival in Rb-null cells is rescued by Rb but not by Rb mutants defective in binding LxCxE proteins. RF-C thus enhances cell survival after DNA damage in an Rb-dependent manner. C1 Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA. Inst Biol Struct JP Ebel, F-38027 Grenoble 1, France. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. RP Fotedar, R (reprint author), Sidney Kimmel Canc Ctr, 10835 Altman Rd, San Diego, CA 92121 USA. FU NCI NIH HHS [R01 CA058320, CA74435]; NIAID NIH HHS [AI31453] NR 44 TC 39 Z9 41 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR PY 2001 VL 7 IS 4 BP 715 EP 727 DI 10.1016/S1097-2765(01)00217-9 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 428LH UT WOS:000168462800003 PM 11336696 ER PT J AU Nakano, K Todo, T Chijiiwa, K Tanaka, M AF Nakano, K Todo, T Chijiiwa, K Tanaka, M TI Therapeutic efficacy of G207, a conditionally replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters SO MOLECULAR THERAPY LA English DT Article DE G207; herpes simplex virus; oncolytic virus therapy; systemic anti-tumor immunity; gallbladder cancer; gene therapy; cancer vaccine ID ANTITUMOR IMMUNITY; SAFETY EVALUATION; TUMOR-THERAPY; CANCER; GLIOMA; TRIAL AB Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 x 10(7) pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment. C1 Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, Fukuoka 8128582, Japan. Harvard Univ, Sch Med, Mol Neurosurg Lab, Neurosurg Serv,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Nakano, K (reprint author), 3-1-1 Maidashi,Higashi Ku, Fukuoka 8128582, Japan. NR 21 TC 29 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD APR PY 2001 VL 3 IS 4 BP 431 EP 437 DI 10.1006/mthe.2001.0303 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 426UV UT WOS:000168367500005 PM 11319903 ER PT J AU Saeki, Y Fraefel, C Ichikawa, T Breakefield, XO Chiocca, EA AF Saeki, Y Fraefel, C Ichikawa, T Breakefield, XO Chiocca, EA TI Improved helper virus-free packaging system for HSV amplicon vectors using an ICP27-deleted, oversized HSV-1 DNA in a bacterial artificial chromosome SO MOLECULAR THERAPY LA English DT Article DE herpes virus; amplicon; helper virus-free; BAC; homologous recombination; site-specific recombination; gene therapy; RecA; Cre/loxP ID EPSTEIN-BARR-VIRUS; ESCHERICHIA-COLI; TETRACYCLINE RESISTANCE; GENE-TRANSFER; NEURAL CELLS; IN-VIVO; SIMPLEX; TYPE-1; EXPRESSION; REPLICATION AB Herpes simplex virus type 1 (HSV-1) amplicons are prokaryotic plasmids containing one or more transcriptional units and two cis-acting HSV-1 sequences: a viral origin of DNA replication and a viral DNA cleavage/packaging signal. In the presence of HSV-1 "helper" functions, amplicons are replicated and packaged into HSV-1 virions. Despite recent improvements in packaging methods, stocks of amplicon vectors are still contaminated with replication-competent helper virus at a frequency of 10(-4)-10(-6). TO overcome this problem, we report that: (i) genetic modifications of HSV-1 genomes can be routinely achieved in Escherichia coli, either by homologous or site-specific recombination, (ii) a novel HSV-1 bacterial artificial chromosome (fHSV Delta pac27 0+), which has a deletion in the essential gene encoding ICP27 and an addition of ICP0 "stuffer" sequences to increase its size to 178 kb, supports the replication and packaging of cotransfected amplicon DNA without generating replication-competent helper virus (<1 helper virus per 10(8) TU amplicon vectors), and (iii) the resulting amplicon stocks have titers of up to 3-10 x 10(8) TU/ml after concentration. Elimination of replication-competent helper virus from HSV-1 amplicon vector stocks further improves safety in gene transfer applications. C1 Harvard Univ, Mol Neurooncol Labs, Massachusetts Gen Hosp, Sch Med,Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med,Mol Neurogenet Unit, Charlestown, MA 02129 USA. Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, Suita, Osaka 5650871, Japan. Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. RP Saeki, Y (reprint author), Harvard Univ, Mol Neurooncol Labs, Massachusetts Gen Hosp, Sch Med,Neurosurg Serv, CNY6119,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01CA69246] NR 30 TC 156 Z9 158 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD APR PY 2001 VL 3 IS 4 BP 591 EP 601 DI 10.1006/mthe.2001.0294 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 426UV UT WOS:000168367500024 PM 11319922 ER PT J AU Brouns, MR Matheson, SF Settleman, J AF Brouns, MR Matheson, SF Settleman, J TI p190 RhoGAP is the principal Src substrate in brain and regulates axon outgrowth, guidance and fasciculation SO NATURE CELL BIOLOGY LA English DT Article ID LONG-TERM POTENTIATION; GTPASE-ACTIVATING PROTEIN; CENTRAL-NERVOUS-SYSTEM; TYROSINE KINASES; MUTANT MICE; C-SRC; NEURITE OUTGROWTH; COMMISSURAL AXONS; CELL-ADHESION; GENE-PRODUCT AB The Src tyrosine kinases have been implicated in several aspects of neural development and nervous system function; however, their relevant substrates in brain and their mechanism of action in neurons remain to be established clearly. Here we identify the potent Rho regulatory protein, p190 RhoGAP (GTPase-activating protein), as the principal Src substrate detected in the developing and mature nervous system. We also find that mice lacking functional p190 RhoGAP exhibit defects in axon guidance and fasciculation, p190 RhoGAP is cc-enriched with F-actin in the distal tips of axons, and overexpressing p190 RhoGAP in neuroblastoma cells promotes extensive neurite outgrowth, indicating that p190 RhoGAP may be an important regulator of Rho-mediated actin reorganization in neuronal growth cones. p190 RhoGAP transduces signals downstream of cell-surface adhesion molecules, and we find that p190-RhoGAP-mediated neurite outgrowth is promoted by the extracellular matrix protein laminin. Together with the fact that mice lacking neural adhesion molecules or Src kinases also exhibit defects in axon outgrowth, guidance and fasciculation, our results suggest that p190 RhoGAP mediates a Src-dependent adhesion signal for neuritogenesis to the actin cytoskeleton through the Rho GTPase. C1 Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, 149 13th St, Boston, MA 02129 USA. OI Matheson, Stephen/0000-0003-0561-8152 NR 50 TC 175 Z9 176 U1 0 U2 5 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2001 VL 3 IS 4 BP 361 EP 367 DI 10.1038/35070042 PG 7 WC Cell Biology SC Cell Biology GA 421CE UT WOS:000168043900014 PM 11283609 ER PT J AU Feske, S Giltnane, J Dolmetsch, R Staudt, LM Rao, A AF Feske, S Giltnane, J Dolmetsch, R Staudt, LM Rao, A TI Gene regulation mediated by calcium signals in T lymphocytes SO NATURE IMMUNOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; RESONANCE ENERGY-TRANSFER; STORE DEPLETION; INOSITOL TRISPHOSPHATE; INTRACELLULAR CALCIUM; TRANSCRIPTION FACTORS; PLASMA-MEMBRANE; CA2+ ENTRY; NF-AT; CELLS AB Modulation of many signaling pathways in antigen-stimulated T and B cells results in global changes in gene expression. Here we investigate the contribution of calcium signaling to gene expression in T cells using cell lines from two severe-combined immunodeficiency patients with several cytokine deficiencies and diminished activation of the transcription factor NFAT nuclear factor of activated T cells. These T cells show a strong defect in transmembrane calcium influx that is also apparent in their B cells and fibroblasts. DNA microarray analysis of calcium entry-deficient and control T cells shows that Ca2+ signals both activate and repress gene expression and are largely transduced through the phosphatase calcineurin. We demonstrate an elaborate network of signaling pathways downstream of the T cell receptor, explaining the complexity of changes in gene expression during T cell activation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. NCI, Metab Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Giltnane, Jennifer/D-2584-2013; OI Feske, Stefan/0000-0001-5431-8178 FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI40127] NR 50 TC 387 Z9 403 U1 1 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2001 VL 2 IS 4 BP 316 EP 324 DI 10.1038/86318 PG 9 WC Immunology SC Immunology GA 420AZ UT WOS:000167982900012 PM 11276202 ER PT J AU Werts, C Tapping, RI Mathison, JC Chuang, TH Kravchenko, V Saint Girons, I Haake, DA Godowski, PJ Hayashi, F Ozinsky, A Underhill, DM Kirschning, CJ Wagner, H Aderem, A Tobias, PS Ulevitch, RJ AF Werts, C Tapping, RI Mathison, JC Chuang, TH Kravchenko, V Saint Girons, I Haake, DA Godowski, PJ Hayashi, F Ozinsky, A Underhill, DM Kirschning, CJ Wagner, H Aderem, A Tobias, PS Ulevitch, RJ TI Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism SO NATURE IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-2; BORRELIA-BURGDORFERI LIPOPROTEINS; INTERROGANS SEROVAR COPENHAGENI; NF-KAPPA-B; OUTER-MEMBRANE; CUTTING EDGE; BACTERIAL LIPOPOLYSACCHARIDE; TREPONEMA-PALLIDUM; MAMMALIAN INFECTION; PATHWAY DISTINCT AB Leptospira interrogans are zoonotic pathogens that have been linked to a recent increased incidence of morbidity and mortality in highly populated tropical urban centers. They are unique among invasive spirochetes in that they contain outer membrane lipopolysaccharide (LPS) as well as lipoproteins. Here we show that both these leptospiral outer membrane constituents activate macrophages through CD14 and the Toll-like receptor 2 (TLR2). Conversely, it seems that TLR4, a central component for recognition of Gram-negative LPS, is not involved in cellular responses to L. interrogans. We also show that for intact L. interrogans, it is LPS, not lipoprotein, that constitutes the predominant signaling component for macrophages through a TLR2 pathway. These data provide a basis for understanding the innate immune response caused by leptospirosis and demonstrate a new ligand specificity for TLR2. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Inst Pasteur, Unite Bacteriol Mol & Med, F-75724 Paris 15, France. Vet Affairs Greater Los Angeles Hlth Care Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany. RP Ulevitch, RJ (reprint author), Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. RI Chuang, Tsung-Hsien/F-9679-2010 FU NIAID NIH HHS [AI-15136, R29 AI034431, R29 AI034431-05]; NIGMS NIH HHS [GM-28485, GM-37696] NR 57 TC 438 Z9 453 U1 7 U2 17 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2001 VL 2 IS 4 BP 346 EP 352 DI 10.1038/86354 PG 7 WC Immunology SC Immunology GA 420AZ UT WOS:000167982900016 PM 11276206 ER PT J AU Rosenthal, N Tsao, L AF Rosenthal, N Tsao, L TI Helping the heart to heal with stem cells SO NATURE MEDICINE LA English DT Editorial Material ID TRANSPLANTATION AB Bone marrow-derived angioblasts may be used to promote cardiac revascularization in the days following a myocardial infarction (pages 430-436). C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Univ Massachusetts, Sch Med, UMass Mem Hlth Ctr, Cardiac Transplantat & Mech Circulatory Assist Pr, Worcester, MA 01655 USA. RP Rosenthal, N (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 7 TC 11 Z9 15 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2001 VL 7 IS 4 BP 412 EP 413 DI 10.1038/86472 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 419QQ UT WOS:000167960500026 PM 11283662 ER PT J AU Klein, MA Kaeser, PS Schwarz, P Weyd, H Xenarios, I Zinkernagel, RM Carroll, MC Verbeek, JS Botto, M Walport, MJ Molina, H Kalinke, U Acha-Orbea, H Aguzzi, A AF Klein, MA Kaeser, PS Schwarz, P Weyd, H Xenarios, I Zinkernagel, RM Carroll, MC Verbeek, JS Botto, M Walport, MJ Molina, H Kalinke, U Acha-Orbea, H Aguzzi, A TI Complement facilitates early prion pathogenesis SO NATURE MEDICINE LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; FOLLICULAR DENDRITIC CELLS; T-DEPENDENT ANTIGEN; B-CELLS; TARGETED DISRUPTION; TONSIL BIOPSY; MICE; SCRAPIE; EXPRESSION; PRP AB New-variant Creutzfeldt-Jakob disease and scrapie are typically initiated by extracerebral exposure to the causative agent, and exhibit early prion replication in lymphoid organs(1,2). In mouse scrapie, depletion of B-lymphocytes prevents neuropathogenesis after intraperitoneal inoculation(3,4), probably due to impaired lymphotoxin-dependent maturation of follicular dendritic cells(5) (FDCs), which are a major extracerebral prion reservoir(6). FDCs trap immune complexes with Fc-gamma receptors and C3d/C4b-opsonized antigens with CD21/CD35 complement receptors. We examined whether these mechanisms participate in peripheral prion pathogenesis. Depletion of circulating immunoglobulins or of individual Fc-gamma receptors had no effect on scrapie pathogenesis if B-cell maturation was unaffected. However, mice deficient in C3, C1q, Bf/C2, combinations thereof(7,8) or complement receptors(9) were partially or fully protected against spongiform encephalopathy upon intraperitoneal exposure to limiting amounts of prions. Splenic accumulation of prion infectivity and PrPSc was delayed, indicating that activation of specific complement components is involved in the initial trapping of prions in lymphoreticular organs early after infection. C1 Univ Zurich, Inst Neuropathol, Zurich, Switzerland. Univ Zurich, Inst Expt Immunol, CH-8091 Zurich, Switzerland. Ctr Blood Res, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Leiden Univ, Med Ctr, Dept Human & Clin Genet, Leiden, Netherlands. Imperial Coll Sch Med, Div Med, Rheumatol Sect, London, England. Washington Univ, Sch Med, Div Rheumatol, St Louis, MO USA. European Mol Biol Lab, Mouse Biol Programme, Monterotondo, Italy. Univ Lausanne, Lausanne Branch, Inst Biochem, CH-1066 Epalinges, Switzerland. Univ Lausanne, Lausanne Branch, Ludwig Inst Canc Res, CH-1066 Epalinges, Switzerland. RP Aguzzi, A (reprint author), Univ Zurich, Inst Neuropathol, Schmelzbergstr, Zurich, Switzerland. RI Aguzzi, Adriano/A-3351-2008; OI Walport, Mark/0000-0001-7220-5273; Xenarios, Ioannis/0000-0002-3413-6841; Aguzzi, Adriano/0000-0002-0344-6708 NR 31 TC 226 Z9 231 U1 0 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2001 VL 7 IS 4 BP 488 EP 492 DI 10.1038/86567 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 419QQ UT WOS:000167960500046 PM 11283678 ER PT J AU Poellinger, A Thomas, R Lio, P Lee, A Makris, N Rosen, BR Kwong, KK AF Poellinger, A Thomas, R Lio, P Lee, A Makris, N Rosen, BR Kwong, KK TI Activation and habituation in olfaction - An fMRI study SO NEUROIMAGE LA English DT Article DE brain mapping; habituation; human; magnetic resonance imaging; neurons; physiology; odors; olfactory pathways; reaction time; odorant; physiological; stimulation ID HUMAN BRAIN ACTIVITY; TOPOGRAPHIC PARCELLATION; RECEPTOR-CELLS; MONKEY; CONNECTIONS; STIMULATION; RESPONSES; CORTEX; BULB; RAT AB This study investigated human BOLD responses in primary and higher order olfactory cortices following presentation of short- and long duration odorant stimuli using a 3-T MR scanner. The goal was to identify temporal differences in the course of the response that might underlie habituation. A short-duration stimulus (9 s) consistently activated the primary olfactory cortex (POC). After a long stimulus (60 s), the temporal form of the response differed in different parts of the olfactory network: (1) The POC (piriform, entorhinal cortex, amygdala) and, interestingly, the hippocampus and, to a certain degree, the anterior insula show a short, phasic increase in the signal, followed by a prolonged decrease below baseline. (2) In the orbitofrontal cortex a sustained increase in activation was seen, This increase lasted approximately as long as the duration of odorant presentation (similar to 60 s). (3) The mediodorsal nucleus of the thalamus and the caudate nucleus responded with an increase in signal which returned to baseline after approximately 15 to 30 s. The correlated biphasic hemodynamic response in the POC, hippocampus, and anterior insula during prolonged olfactory stimulation suggests that these three areas may interact closely with each other in the control of habituation. These results extend recent data which showed habituation of the rat piriform cortex and dissociation between the POC and the orbitofrontal cortex. (C) 2001 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, MGH NMR Ctr, Dept Neurol,Sch Med, Cambridge, MA 02129 USA. Inst Radiol, D-10098 Berlin, Germany. Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm & Crit Care, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Poellinger, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH NMR Ctr, Dept Neurol,Sch Med, Bldg 149,13th St, Cambridge, MA 02129 USA. NR 49 TC 178 Z9 186 U1 2 U2 14 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR PY 2001 VL 13 IS 4 BP 547 EP 560 DI 10.1006/nimg.2000.0713 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 413TR UT WOS:000167628500001 PM 11305885 ER PT J AU Price, ER Fisher, DE AF Price, ER Fisher, DE TI Sensorineural deafness and pigmentation genes: Melanocytes and the Mitf transcriptional network SO NEURON LA English DT Review ID WAARDENBURG SYNDROME TYPE-2; MICROPHTHALMIA; EXPRESSION; SOX10; PAX3; DIFFERENTIATION; LINKS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. NR 20 TC 53 Z9 54 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR PY 2001 VL 30 IS 1 BP 15 EP 18 DI 10.1016/S0896-6273(01)00259-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 427NR UT WOS:000168412900007 PM 11343641 ER PT J AU Bar, M Tootell, RBH Schacter, DL Greve, DN Fischl, B Mendola, JD Rosen, BR Dale, AM AF Bar, M Tootell, RBH Schacter, DL Greve, DN Fischl, B Mendola, JD Rosen, BR Dale, AM TI Cortical mechanisms specific to explicit visual object recognition (vol 29, pg 529, 2001) SO NEURON LA English DT Correction C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Bar, M (reprint author), Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. NR 1 TC 0 Z9 0 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR PY 2001 VL 30 IS 1 BP 299 EP 299 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 427NR UT WOS:000168412900029 ER PT J AU Nutt, CL Matthews, RT Hockfield, S AF Nutt, CL Matthews, RT Hockfield, S TI Glial tumor invasion: A role for the upregulation and cleavage of BEHAB/brevican SO NEUROSCIENTIST LA English DT Review DE glioma; invasion; extracellular matrix; BEHAB; brevican; ADAMTS ID HYALURONAN-BINDING PROTEIN; CHONDROITIN SULFATE PROTEOGLYCAN; AGGRECAN-DEGRADING ACTIVITY; HUMAN SYNOVIAL-FLUID; EXTRACELLULAR-MATRIX; CHROMOSOMAL LOCALIZATION; ADAMTS FAMILY; RAT-BRAIN; THROMBOSPONDIN MOTIFS; CORTICAL DEVELOPMENT AB Glial tumors, gliomas, are the most common primary intracranial tumors. Their distinct ability to invade the normal surrounding tissue makes them difficult to control and nearly impossible to completely remove surgically, and it accounts for the extraordinarily high lethality associated with gliomas. The ability of these transformed glial cells to invade the normal surrounding tissue is relatively unique in the adult CNS, which under most circumstances, is inhibitory to cell movement. The extracelluar matrix (ECM) can modulate, in part, the permissiveness of a tissue to cell movement. Accordingly, the ability of gliomas to modify the ECM of the CNS may mediate the invasiveness of these cells. One ECM molecule that shows dramatic upregulation in gliomas is BEHAB (brain enriched hyaluronan binding)/brevican, a brain-specific chondroitin sulfate proteoglycan. BEHAB/brevican expression is also upregulated during periods of increased glial cell motility in development and following brain injury. Experimental evidence suggests that in glioma, in addition to upregulation of BEHAB/brevican, proteolytic processing of the full-length protein also may contribute to invasion. Here, the authors present a review of the literature on glial tumor invasion by modulation of the ECM and propose a two-step model for BEHAB/brevican's role in this process. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. RI Nutt, Catherine/K-8794-2012 FU NINDS NIH HHS [2T32-NSO7224-15, R01NS35228] NR 56 TC 32 Z9 32 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD APR PY 2001 VL 7 IS 2 BP 113 EP 122 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 417AG UT WOS:000167812500014 PM 11496922 ER PT J AU Chen, CC Bellon, RJ Ogilvy, CS Putnam, CM AF Chen, CC Bellon, RJ Ogilvy, CS Putnam, CM TI Aneurysms of the lateral spinal artery: Report of two cases SO NEUROSURGERY LA English DT Article DE aneurysm; spinal artery; subarachnoid hemorrhage; vertebral artery stenosis ID ARTERIOVENOUS MALFORMATION; SUBARACHNOID HEMORRHAGE; INTRACRANIAL ANEURYSMS; CORD AB OBJECTIVE AND IMPORTANCE: The goal of this report was to describe aneurysms arising from the lateral spinal artery. The locations of aneurysms contributing to subarachnoid hemorrhage (SAH) have been well characterized and are primarily in the circle of Willis or at the bifurcation points of the internal carotid artery or the vertebrobasilar system. Although the spinal arteries are also in direct communication with the subarachnoid space, aneurysms of these arteries that lead to SAH are rare. To date, only aneurysms of the anterior and posterior spinal arteries have been described. In this communication, we report two patients with aneurysms of the lateral spinal artery who presented with SAH. CLINICAL PRESENTATION: Review of our neurointerventional database from 1997 to the present revealed two patients with lateral spinal artery aneurysms. The medical records, as well as the operative and radiological findings, were reviewed for both patients. In both cases, the lateral spinal arteries were involved as collateral pathways for occlusive vertebral lesions, suggesting hemodynamic stress as a cause. INTERVENTION: Endovascular treatment was attempted in both cases and was successful in one; open surgery, with aneurysm resection, was performed in the other case. We review the vascular anatomic features of the spinal cord as they relate to the lateral spinal artery, as well as treatment options for lateral spinal artery aneurysms. CONCLUSION: Lateral spinal artery aneurysms are a rare cause of SAH. Both endovascular and surgical treatment options are available. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Intervent Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Putnam, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Intervent Neuroradiol, 55 Fruit St,GRB-289, Boston, MA 02114 USA. RI Chen, Clark/C-8714-2013 OI Chen, Clark/0000-0001-6258-9277 NR 25 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD APR PY 2001 VL 48 IS 4 BP 949 EP 953 DI 10.1097/00006123-200104000-00057 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 416YN UT WOS:000167808200128 PM 11322459 ER PT J AU Thadhani, R Ecker, JL Kettyle, E Sandler, L Frigoletto, FD AF Thadhani, R Ecker, JL Kettyle, E Sandler, L Frigoletto, FD TI Pulse pressure and risk of preeclampsia: A prospective study SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID MEAN ARTERIAL-PRESSURE; BLOOD-PRESSURE; PREGNANCY; HYPERTENSION; CIRCULATION; TRIMESTER AB Objective: To find whether pulse pressure, a measure of arterial compliance, is associated early in pregnancy with increased risk of developing preeclampsia. Methods: In a prospective cohort of 576 nulliparas, we examined blood pressures throughout pregnancy and at 6-8 weeks postpartum. Measurements during weeks 7-15, 16-24, and 25-38 of gestation were pooled to find averages for each period. Outcomes assessed were gestational hypertension and preeclampsia. Logistic regression analysis was used to develop relative risks and 95% confidence intervals. Results: We confirmed 34 (5.9%) cases of preeclampsia, 32 (5.6%) cases of gestational hypertension, and 510 normotensive women. Mean systolic and diastolic blood pressures and mean arterial pressures were elevated throughout pregnancy in women who developed hypertensive disorders of pregnancy compared with normotensive women. pulse pres sure at 7-15 weeks was significantly higher in women who developed preeclampsia (45 +/- 6 mmHg) than in those who developed gestational hypertension (41 +/- 7 mmHg, P = .03) and normotensive women (41 +/- 8 mmHg, P = .01). Examined in tertiles, increasing pulse pressure was associated with increasing, risk of developing preeclampsia (P for trend = .01) but not gestational hypertension (P for trend = .95). After adjustment for potential confounders, a 1-mmHg rise in early pregnancy pulse pressure was associated with a 6% (95% confidence interval: 1, 10) increase in risk for developing preeclampsia but not gestational hypertension (relative risk: 1%; 95% confidence interval: -1, 6). Beyond 15 weeks' gestation, differences between groups diminished, but women with any hypertensive disorder had higher pulse pressures than women with uncomplicated pregnancies. Conclusion: Elevated pulse pressure, indicating poor arterial compliance, was evident early in pregnancies of women who subsequently developed preeclampsia. (C) 2001 by The American College of Obstetricians and Gynecologists. C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, 55 Fruit St,Founders 036, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-03804] NR 27 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2001 VL 97 IS 4 BP 515 EP 520 DI 10.1016/S0029-7844(00)01192-3 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 416ZP UT WOS:000167810800007 PM 11275020 ER EF