FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Spencer, KM AF Spencer, KM TI Abnormal neural synchrony in schizophrenia SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 29-NOV 02, 2003 CL CHICAGO, ILLINOIS SP Soc Psychophysiol Res C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2003 VL 40 SU 1 BP S17 EP S17 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 715BV UT WOS:000184951400066 ER PT J AU Freudenreich, O Stern, TA AF Freudenreich, O Stern, TA TI Clinical experience with the management of schizophrenia in the general hospital SO PSYCHOSOMATICS LA English DT Review ID NEUROLEPTIC MALIGNANT SYNDROME; CHRONICALLY MENTALLY-ILL; PSYCHIATRIC-PATIENTS; CLOZAPINE WITHDRAWAL; INTRAVENOUS HALOPERIDOL; LIPID ABNORMALITIES; CATATONIC SYNDROME; DIABETES-MELLITUS; INFORMED CONSENT; MEDICAL ILLNESS AB On the basis of e experience with 74 psychiatric consultations involving patients with schizophrenia admitted to a general hospital medical or surgical ward over a 17-month period (3% of the psychiatric consultations during that period), the authors identified 10 types of problems leading to requests for consultation. The authors used these categories to organize recommendations for management of patients with schizophrenia in the general medical hospital. In addition to conducting conventional consultations, the consultation psychiatrist in such cases often has a role in educating hospital staff about Schizophrenia and in serving as a physician for the mentally ill. C1 Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Freudenreich, O (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. NR 108 TC 7 Z9 7 U1 4 U2 7 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2003 VL 44 IS 1 BP 12 EP 23 DI 10.1176/appi.psy.44.1.12 PG 12 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 631MG UT WOS:000180171100002 PM 12515833 ER PT J AU Chang, G McGarigle, C Koby, D Antin, JH AF Chang, G McGarigle, C Koby, D Antin, JH TI Symptoms of pain and depression in related marrow donors: Changes after transplant SO PSYCHOSOMATICS LA English DT Article ID PSYCHOSOCIAL-ASPECTS; DONATION; PROGRAM; FAMILY; EXPERIENCES; PATIENT; ISSUES C1 Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chang, G (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. FU NIAAA NIH HHS [AA-00289] NR 38 TC 5 Z9 6 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2003 VL 44 IS 1 BP 59 EP 64 DI 10.1176/appi.psy.44.1.59 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 631MG UT WOS:000180171100008 PM 12515839 ER PT J AU Huffman, J Stern, TA AF Huffman, J Stern, TA TI Acute psychiatric manifestations of stroke: A clinical case conference SO PSYCHOSOMATICS LA English DT Article ID POSTSTROKE MOOD DISORDERS; DOUBLE-BLIND TREATMENT; QUALITY-OF-LIFE; ELECTROCONVULSIVE-THERAPY; DEPRESSIVE SYMPTOMS; BRAIN INJURY; CEREBROVASCULAR LESIONS; CATASTROPHIC REACTION; COGNITIVE IMPAIRMENT; GENERALIZED ANXIETY C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02178 USA. RP Stern, TA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Warren 605,Fruit St, Boston, MA 02114 USA. EM TStern@partners.org NR 84 TC 10 Z9 11 U1 4 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2003 VL 44 IS 1 BP 65 EP 75 DI 10.1176/appi.psy.44.1.65 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 631MG UT WOS:000180171100009 PM 12515840 ER PT J AU Heldt, E Manfro, GG Kipper, L Blaya, C Maltz, S Isolan, L Hirakata, VN Otto, MW AF Heldt, E Manfro, GG Kipper, L Blaya, C Maltz, S Isolan, L Hirakata, VN Otto, MW TI Treating medication-resistant panic disorder: Predictors and outcome of cognitive-behavior therapy in a Brazilian public hospital SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE panic disorder; cognitive behavior therapy; depression; defense mechanisms; comorbidity ID MAJOR DEPRESSION; PSYCHIATRIC INTERVIEW; CASE SERIES; DISCONTINUATION; AGORAPHOBIA; EXPOSURE; COMBINATION; IMIPRAMINE; SYMPTOMS; CONTEXT AB Background: In Brazil, treatment of panic disorder is most frequently initiated with pharmacotherapy, but only half of the patients can be expected to be panic free after medication. Studies have suggested that individual or group cognitive-behavior therapy (CBT) is an effective treatment strategy for panic patients who have failed to respond to pharmacotherapy. Methods: Thirty-two patients diagnosed with panic disorder with agoraphobia having residual symptoms despite being on an adequate dose of medication were treated with 12 weeks of group CBT. The outcome was evaluated for panic frequency and severity, generalized anxiety, and global severity. Comorbid conditions, a childhood history of anxiety, and defense mechanism styles were assessed as potential predictors of treatment response. Results: Twenty-nine patients completed the 12-week protocol. Treatment was associated with significant reductions in symptom severity on all outcome measures (p < 0.001). Patients with depression had a poorer outcome of the treatment (p = 0.01) as did patients using more neurotic (p = 0.002) and immature defenses (p = 0.05). Conclusion: Consistent with previous reports, we found that CBT was effective for our sample of treatment-resistant patients. Among these patients, depression as well as neurotic defense style was associated with a poorer outcome. The use of CBT in Brazil for treatment-resistant and other panic patients is encouraged. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Cognit Behav Therapy Program, Boston, MA 02114 USA. Univ Fed Rio Grande Sul, Postgrad Program Med Sci Psychiat, Porto Alegre, RS, Brazil. Hosp Clin Porto Alegre, Anxiety Disorder Program, Porto Alegre, RS, Brazil. RP Manfro, GG (reprint author), Luis Manoel Gonzaga,630-11, BR-90470280 Porto Alegre, RS, Brazil. RI Manfro, Gisele/B-7020-2009; Hirakata, Vania/I-3012-2012 OI Hirakata, Vania/0000-0003-4645-2080 NR 32 TC 51 Z9 53 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD JAN-FEB PY 2003 VL 72 IS 1 BP 43 EP 48 DI 10.1159/000067188 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 638EB UT WOS:000180557700006 PM 12466637 ER PT J AU Levine, SM Lambiase, RE Petchprapa, CN AF Levine, SM Lambiase, RE Petchprapa, CN TI Cortical lesions of the tibia: Characteristic appearances at conventional radiography SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 86th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 26-DEC 01, 2000 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE tibia, abnormalities; tibia, fractures; tibia, neoplasms AB Lesions that involve the cortex of the tibia are fairly common in radiology practice. However, the number of diseases that involve the tibial cortex is great, and it can be difficult to arrive at a limited differential diagnosis from radiographic findings. Categorization of lesions of the tibia into those that cause cortical destruction and those that cause cortical proliferation can help narrow the broad differential diagnosis. Lesions that cause cortical destruction include nonossifying fibroma, fibrous dysplasia, osteofibrous dysplasia, aneurysmal bone cyst, giant cell tumor, eosinophilic granuloma, Ewing sarcoma, neurofibromatosis, adamantinoma, osteoblastoma, chondromyxoid fibroma, hemangioendothelioma, renal cell metastatic disease, hemangioma, and hemangiopericytoma. Lesions that cause cortical proliferation include osteochondroma, stress fracture, osteoid osteoma, periosteal osteogenic sarcoma, diaphyseal dysplasia, venous stasis, cellulitis, chronic osteomyelitis, osteopathia striatum, and melorheostosis. Conventional radiography along with clinical and pathologic data can aid in diagnosis of the wide variety of disease processes that involve the tibial cortex. C1 Brown Univ, Rhode Isl Hosp, Sch Med, Dept Diagnost Imaging, Providence, RI 02903 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Lambiase, RE (reprint author), Brown Univ, Rhode Isl Hosp, Sch Med, Dept Diagnost Imaging, 593 Eddy St, Providence, RI 02903 USA. OI PETCHPRAPA, CATHERINE/0000-0003-2663-8603 NR 24 TC 45 Z9 48 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 JAN-FEB PY 2003 VL 23 IS 1 BP 157 EP 177 DI 10.1148/rg.231015088 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 635TY UT WOS:000180416500013 PM 12533651 ER PT J AU Halpern, EF Gazelle, GS AF Halpern, EF Gazelle, GS TI Probability in radiology SO RADIOLOGY LA English DT Article DE statistical analysis AB In this article, a summary of the basic rules of probability using examples of their application in radiology is presented. Those rules describe how probabilities may be combined to obtain the chance of "success" with either of two diagnostic or therapeutic procedures or with both. They define independence and relate it to the conditional probability. They describe the relationship (Bayes rule) between sensitivity, specificity, and prevalence on the one hand and the positive and negative predictive values on the other. Finally, the two distributions most commonly encountered in statistical models of radiologic data are presented: the binomial and normal distributions. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Dept Radiol, DATA Grp, Boston, MA 02114 USA. RP Halpern, EF (reprint author), Massachusetts Gen Hosp, Dept Radiol, DATA Grp, 0 Emerson Pl,Suite 2H, Boston, MA 02114 USA. NR 7 TC 13 Z9 13 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2003 VL 226 IS 1 BP 12 EP 15 DI 10.1148/radiol.2261011712 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 630KR UT WOS:000180106500003 PM 12511662 ER PT J AU Mayo-Smith, WW Rhea, JT Smith, WJ Cobb, CM Gareen, IF Dorfman, GS AF Mayo-Smith, WW Rhea, JT Smith, WJ Cobb, CM Gareen, IF Dorfman, GS TI Transportable versus fixed platform CT scanners: Comparison of costs SO RADIOLOGY LA English DT Article DE computed tomography (CT), utilization; cost-effectiveness; economics, medical; radiology and radiologists, socioeconomic issues ID TECHNICAL COST; RADIOLOGY AB PURPOSE: To compare the aggregate hospital technical costs of a transportable computed tomographic (CT) scanner used to image patients in an intensive care unit with those of a fixed platform CT scanner in the radiology department. MATERIALS AND METHODS: Direct fixed costs (ie, machine and service contract costs) and direct variable costs (ie, personnel costs) were calculated. Indirect costs, including space costs and departmental overhead, were calculated. Total costs were calculated as the sum of indirect, direct fixed, and direct variable costs. Personnel costs were calculated from time-motion analyses involving 95 patients who underwent brain CT with either a transportable (n = 51) or a fixed platform (n = 44) CT scanner. Costs per examination were calculated by using both low- and high-examination-volume models and compared with use of the Wilcoxon rank sum test. RESULTS: The total cost per examination for the transportable scanner range 1 d from $108.98 to $167.20 for the high- and low-volume models. Total cost per examination for the fixed platform scanner ranged from $75.24 to $112.39 for the high- and low-volume models. For the transportable scanner, direct fixed, variable, and overhead costs were $87.05, $70.73, and $9.42 per examination, respectively, with low-volume model. The corresponding costs for the fixed platform scanner were $46.66, $55.69, and $10.04, respectively. CONCLUSION: The technical cost of using an in-hospital transportable CT scanner is higher than that of using a fixed platform scanner. (C) RSNA 2002. C1 Brown Univ, Rhode Isl Hosp, Sch Med, Dept Radiol, Providence, RI 02903 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. RP Mayo-Smith, WW (reprint author), Brown Univ, Rhode Isl Hosp, Sch Med, Dept Radiol, 593 Eddy St, Providence, RI 02903 USA. RI Gareen, Ilana/I-2816-2014 OI Gareen, Ilana/0000-0002-0457-5595 NR 13 TC 5 Z9 5 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2003 VL 226 IS 1 BP 63 EP 68 DI 10.1148/radiol.2261012047 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 630KR UT WOS:000180106500010 PM 12511669 ER PT J AU Rosenthal, DI Marota, JJA Hornicek, FJ AF Rosenthal, DI Marota, JJA Hornicek, FJ TI Osteoid osteoma: Elevation of cardiac and respiratory rates at biopsy needle entry into tumor in 10 patients SO RADIOLOGY LA English DT Article DE bones, biopsy; osteoma AB PURPOSE: To evaluate changes in cardiac and respiratory rates in a consecutive series of patients who underwent percutaneous treatment for lesions presumed to be osteoid osteoma in whom general anesthesia was established. MATERIALS AND METHODS: Changes in cardiac and respiratory rates were evaluated after establishment of stable general anesthesia in 14 patients who underwent needle biopsy and radio-frequency treatment. Cardiac and respiratory rates were recorded at penetration of skin, muscle, periosteum, cortex, and tumor. Treatment was performed before the biopsy report was available. RESULTS: Biopsy results revealed osteoid osteoma in 10 patients, chondroblastoma in one, and a herniation pit in one. Results in the two remaining patients were nondiagnostic and were excluded. Puncture of skin, muscle, and periosteum caused no detectable change. However, in the 10 patients with biopsy-proved osteoid osteoma, puncture of the tumor caused the mean cardiac rate to increase an average of 26 beats per minute (40%) to 91 (range, 62-114; P < .001) and the mean respiratory rate to increase an average of 12 breaths per minute (50%) to a mean of 37 (range, 25-52; P < .001). These changes occurred within seconds of tumor puncture and were often the first indication to the surgeon that the tumor had been entered. In the two patients with other diagnoses at biopsy, no such change was apparent. CONCLUSION: Mean cardiac and respiratory rates increase significantly at needle puncture of osteoid osteoma. (C) RSNA, 2002. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02114 USA. RP Rosenthal, DI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 199 Cambridge St, Boston, MA 02114 USA. NR 17 TC 18 Z9 20 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2003 VL 226 IS 1 BP 125 EP 128 DI 10.1148/radiol.2261011993 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 630KR UT WOS:000180106500019 PM 12511680 ER PT J AU Bremer, C Mustafa, M Bogdanov, A Ntziachristos, V Petrovsky, A Weissleder, R AF Bremer, C Mustafa, M Bogdanov, A Ntziachristos, V Petrovsky, A Weissleder, R TI Steady-state blood volume measurements in experimental tumors with different angiogenic burdens - A study in mice SO RADIOLOGY LA English DT Article DE angiogenesis; contrast media, experimental studies; experimental study; neoplasms, experimental studies; neoplasms, radionuclide studies ID SUPERPARAMAGNETIC IRON-OXIDE; MR CONTRAST AGENTS; CERVICAL-CARCINOMA; FERUMOXIDES; FERUMOXTRAN; CANCER; MODEL AB PURPOSE: To experimentally validate the effectiveness of magnetic resonance (MR) imaging enhanced with long-circulating iron oxide for measurement of vascular volume fractions (VVFs) as indicators of angiogenesis in different experimental tumor models. MATERIALS AND METHODS: Tumors with differing degrees of angiogenesis-9L rodent gliosarcoma, DU4475 human mammary adenocarcinoma, HT1080 human fibrosarcoma, and EOMA hemangioendothelioma-were implanted in nude mice. Tumoral VVFs were measured at submillimeter voxel resolutions by using 1.5-TMR imaging. A technetium-labeled intravascular radiotracer was injected into a subset of the animals to validate the MR imaging measurements. Microvessel density and vascular endothelial growth factor (VEGF) also were measured. Statistical analysis was performed with analysis of variance. RESULTS: High-resolution multisection MR maps of tumor blood volume were obtained in all tumor models. Mean tumoral VVF differed significantly among the different tumors: 2.1% +/- 0.3 (standard error of mean) for 9L gliosarcoma, 3.1% +/- 0.4 for DU4475 mammary adenocarcinoma, 5.5% +/- 0.8 for HT1080 fibrosarcoma, and 6.6% +/- 0.9 for EOMA hemangioendothelioma (P<.01). There was a strong correlation between the MR imaging and radiotracer measurements. There was considerable intra- and intertumoral heterogeneity among the VVFs. MR imaging measurements were in accordance with conventional measurements of angiogenesis, such as microvessel density count and VEGF. CONCLUSION: Measurements of tumoral VVF at high-resolution MR imaging with long-circulating iron oxide are feasible and correlate with angiogenic burden in experimental tumor models. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,S406, Charlestown, MA 02129 USA. NR 28 TC 70 Z9 74 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2003 VL 226 IS 1 BP 214 EP 220 DI 10.1148/radiol.2261012140 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 630KR UT WOS:000180106500032 PM 12511693 ER PT J AU Lomax, AJ Goitein, M Adams, J AF Lomax, AJ Goitein, M Adams, J TI Intensity modulation in radiotherapy: photons versus protons in the paranasal sinus SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE IMRT; intensity modulated proton therapy; proton therapy; treatment plan comparison ID RADIATION-THERAPY; POTENTIAL ROLE; MULTILEAF COLLIMATION; DOSE CALCULATION; NORMAL TISSUE; OPTIMIZATION; TUMORS; BEAMS; IRRADIATION; TOLERANCE AB Purpose: The purpose of this study is to investigate whether successive tightening of normal tissue constraints on an intensity modulated X-ray therapy plan might be able to improve it to the point of clinical comparability with the corresponding intensity modulated proton therapy plan. Materials and methods: Photon and proton intensity modulated plans were calculated for a paranasal sinus case using nominal dose constraints. Additional photon plans were then calculated in an effort to match the dose-volume histograms of the critical structures to those of the proton plan. Results: On reducing the low dose contribution to both orbits in the photon plan by tightening the constraints on these structures, an increased dose heterogeneity across the target resulted. When all critical structures were more strictly constrained, target dose homogeneity and conformity was further compromised. An increased integral dose to the non-critical normal tissues was observed for the photon plans as dose was progressively removed from the critical structures. Conclusions: Both modalities were found to provide comparable target volume conformation and sparing of critical structures, when the nominal dose constraints were applied. However, the use of intensity modulated protons provided the only method by which critical structures could be spared at all dose levels, whilst simultaneously providing acceptable dose homogeneity within the target volume. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Paul Scherrer Inst, Div Radiat Oncol, CH-5232 Villigen, Switzerland. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Lomax, AJ (reprint author), Paul Scherrer Inst, Div Radiat Oncol, CH-5232 Villigen, Switzerland. NR 28 TC 61 Z9 62 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JAN PY 2003 VL 66 IS 1 BP 11 EP 18 DI 10.1016/S0167-8140(02)00308-0 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 695ZG UT WOS:000183859800002 PM 12559516 ER PT J AU Hayashi, T Faustman, DL AF Hayashi, T Faustman, DL TI Role of defective apoptosis in type 1 diabetes and other autoimmune diseases SO RECENT PROGRESS IN HORMONE RESEARCH, VOL 58 SE RECENT PROGRESS IN HORMONE RESEARCH LA English DT Review ID NF-KAPPA-B; SYSTEMIC-LUPUS-ERYTHEMATOSUS; BETA-CELL DESTRUCTION; FAS LIGAND EXPRESSION; NECROSIS-FACTOR-ALPHA; UBIQUITIN-PROTEASOME PATHWAY; SEVERE LIVER DEGENERATION; IN-VITRO APOPTOSIS; MICE LACKING; NOD MICE AB Lymphocyte development, selection, and education are strictly controlled to prevent autoimmunity, with potentially autoreactive cells being removed by apoptosis. Dysregulation of apoptosis is a central defect in diverse murine autoimmune diseases. In murine models of autoimmune lupus, for example, mutations in the death receptor Fas (CD95) or in its ligand, Fast, (CD95L), have been identified and shown to render lymphoid cells resistant to apoptosis. In contrast, select lymphoid subpopulations of mice with autoimmune diabetes manifest an increased susceptibility to apoptosis as a result of impaired activation of the transcription factor nuclear factor-kappa B (NF-kappaB), which normally protects cells against tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. The genetic basis of this defect in NF-kappaB activation is a mutation in the promoter-enhancer region of a gene that encodes an essential subunit (LMP2) of the proteasome. Although no specific genetic defects have been identified in most common forms of human autoimmune disease, functional assays consistently demonstrate heightened apoptosis attributable to multiple death signaling pathways. C1 Massachusetts Gen Hosp, Immunobiol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Hayashi, T (reprint author), Massachusetts Gen Hosp, Immunobiol Lab, Charlestown, MA 02129 USA. NR 116 TC 23 Z9 24 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4410 USA SN 0079-9963 J9 RECENT PROG HORM RES PY 2003 VL 58 BP 131 EP 153 DI 10.1210/rp.58.1.131 PG 23 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BW63Z UT WOS:000182666800006 PM 12795417 ER PT J AU Shenouda, PE Cunningham, BJ AF Shenouda, PE Cunningham, BJ TI Assessing the superiority of saline versus air for use in the epidural loss of resistance technique: A literature review SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Review ID EXTRADURAL SPACE; INTRATHECAL AIR; ANALGESIA; ANESTHESIA; PNEUMOCEPHALUS; CATHETERS; HEADACHE; PUNCTURE; BLOCK; IDENTIFICATION C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Dallas Spine Care, Dallas, TX USA. RP Shenouda, PE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin Bldg,309, Boston, MA 02114 USA. NR 41 TC 35 Z9 38 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 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD JAN-FEB PY 2003 VL 28 IS 1 BP 48 EP 53 DI 10.1053/rapm.2003.50009 PG 6 WC Anesthesiology SC Anesthesiology GA 644DU UT WOS:000180903300010 PM 12567344 ER PT B AU Sodroski, J AF Sodroski, J BE Vicari, M Dodet, B Girard, M TI Aspects of human immunodeficiency virus type 1 neutralization by CD4-induced antibodies SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 13th International Cent Gardes Symposium CY OCT 27-29, 2002 CL ANNECY, FRANCE SP Merieux Fdn, Aventis Pasteur, Participat IAVI ID GP120 ENVELOPE GLYCOPROTEIN; RECEPTOR-BINDING; HIV-1 ENTRY; EPITOPES; PEPTIDES; TERMINUS; CCR-5 C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-389-6 PY 2003 BP 25 EP 27 PG 3 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BX14W UT WOS:000184433300005 ER PT B AU Ruprecht, RM AF Ruprecht, RM BE Vicari, M Dodet, B Girard, M TI Neutralizing antibodies: a potent line of defense against acute and chronic simian-human immunodeficiency virus infection SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 13th International Cent Gardes Symposium CY OCT 27-29, 2002 CL ANNECY, FRANCE SP Merieux Fdn, Aventis Pasteur, Participat IAVI ID HUMAN MONOCLONAL-ANTIBODIES; CYTOTOXIC T-LYMPHOCYTES; NEONATAL MACAQUES; PASSIVE-IMMUNIZATION; RHESUS-MONKEYS; PRIMATE MODEL; CLADE-B; TYPE-1; VACCINE; CHALLENGE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-389-6 PY 2003 BP 45 EP 50 PG 6 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BX14W UT WOS:000184433300008 ER PT J AU Nakatani, Y Ogryzko, V AF Nakatani, Y Ogryzko, V TI Immunoaffinity purification of mammalian protein complexes SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID HISTONE ACETYLASE COMPLEX; RNA-POLYMERASE-II; TRANSCRIPTION; GENES; CELLS; TAFS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Andre Lwoff, CNRS, Lab Oncogenese Differenciat & Transduct Signal, UPR 9079, Villejuif, France. RP Nakatani, Y (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 18 TC 178 Z9 179 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 430 EP 444 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300037 PM 14712665 ER PT J AU Page, KR Karakousis, PC Maslow, JN AF Page, KR Karakousis, PC Maslow, JN TI Postoperative pneumococcal cellulitis in systemic lupus erythematosus SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID SOFT-TISSUE INFECTIONS; STREPTOCOCCUS-PNEUMONIAE; NEISSERIAL AB This paper reports a case of nosocomial pneumococcal cellulitis that developed following a lymph-node biopsy in a woman being treated with high-dose intravenous corticosteroids for systemic lupus erythematosis (SLE). Her rapid and severe clinical deterioration was similar to that caused by group A streptococcus. The risk factors for the development of nosocomial pneumococcal cellulitis as a complication of SLE are reviewed and preventive measures discussed. C1 Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. RP Maslow, JN (reprint author), V A Med Ctr, ACOS Res, 151,Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PY 2003 VL 35 IS 2 BP 141 EP 143 DI 10.1080/0036554021000027002 PG 3 WC Infectious Diseases SC Infectious Diseases GA 664UE UT WOS:000182079500015 PM 12693569 ER PT J AU Kee, KS Green, MF Mintz, J Brekke, JS AF Kee, KS Green, MF Mintz, J Brekke, JS TI Is emotion processing a predictor of functional outcome in schizophrenia? SO SCHIZOPHRENIA BULLETIN LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Research-in-Psychopathology CY NOV 18-21, 1999 CL MONTREAL, CANADA SP Soc Res Psychopathol DE schizophrenia; emotion perception; affect recognition; social cognition; functional outcome; psychosocial functioning ID FACIAL-AFFECT RECOGNITION; CHRONICALLY MENTALLY-ILL; SUBJECTIVE EXPERIENCE; AFFECTIVE-DISORDERS; AFFECT PERCEPTION; DEFICIT; REHABILITATION; COGNITION; BEHAVIOR; SERVICES AB Deficits in the ability to perceive facial and vocal emotion expression are common in schizophrenia. However, relatively little is known about how such deficits might affect functional outcomes. This prospective study examined cross-sectional and longitudinal relationships between perception of emotion and aspects of psychosocial functioning, including family relationships, social relationships, work functioning, and independent living/self-care in 94 clinically stabilized schizophrenia outpatients from five community-based rehabilitation programs. Emotion perception (facial emotion, voice emotion, and affect perception) and psychosocial outcome (Strauss and Carpenter Outcome Scale and Role Functioning Scale) were assessed at baseline and after 12 months of psychosocial rehabilitation. Significant associations were found between perception of emotion and work functioning/independent living both cross-sectionally and prospectively over the 12 months. Causal explanatory models suggested that perception of emotion might cause work functioning/independent living outcome over 1 year. The results remained significant when conceptual disorganization was statistically controlled. We did not find differences between men and women in the correlations between emotion perception and work functioning/independent living. Associations between social functioning/family relationships and perception of emotion were not significant. These findings suggest that emotion processing is a key determinant of work functioning/independent living for individuals with serious mental illness. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. MIRECC, VA VISN 22, Los Angeles, CA USA. Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. RP Kee, KS (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Biobehav Sci, 11301 Wilshire Blvd,MIRECC 210A,Bldg 210, Los Angeles, CA 90073 USA. FU NIMH NIH HHS [MH53282] NR 43 TC 204 Z9 209 U1 1 U2 6 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2003 VL 29 IS 3 BP 487 EP 497 PG 11 WC Psychiatry SC Psychiatry GA 742NJ UT WOS:000186523700007 PM 14609242 ER PT J AU Cannon, TD van Erp, TGM Bearden, CE Loewy, R Thompson, P Toga, AW Huttunen, MO Keshavan, MS Seidman, LJ Tsuang, MT AF Cannon, TD van Erp, TGM Bearden, CE Loewy, R Thompson, P Toga, AW Huttunen, MO Keshavan, MS Seidman, LJ Tsuang, MT TI Early and late neurodevelopmental influences in the prodrome to schizophrenia, contributions of genes, environment, and their interactions SO SCHIZOPHRENIA BULLETIN LA English DT Review DE schizophrenia; prodromal; genes; environment; vulnerability; neurodevelopment; MRI ID HIPPOCAMPAL VOLUME REDUCTIONS; FIRST-EPISODE SCHIZOPHRENIA; EARLY-ONSET SCHIZOPHRENIA; EDINBURGH HIGH-RISK; WORKING-MEMORY; PROSPECTIVE COHORT; PREFRONTAL CORTEX; UNAFFECTED SIBLINGS; BRAIN-DEVELOPMENT; TWINS DISCORDANT AB Both early (i.e., pre- and perinatal periods) and late (i.e., adolescent period) neurodevelopmental processes are thought to participate in the etiology and pathophysiology of schizophrenia. However, whether markers of these processes would be expected to predict an imminent onset of psychosis, as is hoped in the current generation of prodromal research programs, depends on whether their disruptions result from genetic factors shared by patients and some of their unaffected relatives, nongenetic factors specific to those who manifest the illness phenotype, or combinations of these sets of influences. Here we present recent work deriving primarily from high-risk and family-study (i.e., "genetic high-risk") designs, which provide a framework for investigating the neural changes that may occur proximally to the initial onset of psychosis. This work indicates that some of the alterations in brain function and structure in schizophrenia are primarily genetically mediated and also appear in some of patients' unaffected first degree relatives, while other alterations are present in individuals who manifest the illness phenotype but not in relatives at genetic risk (Cannon et al. 2002a, 2002c; Van Erp et al. 2002). Whereas the primarily genetically mediated deficits shared by at-risk but nonsymptomatic relatives are not likely to show differential change in the premorbid period and may be necessary but clearly not sufficient for the development of psychotic symptoms, the deficits specific to patients who manifest the illness phenotype are good candidates for marking the neurobiological processes associated with the emergence of psychotic symptoms at the time of schizophrenia onset. Preliminary results from longitudinal studies of individuals ascertained initially in a prodromal (i.e., "clinical high-risk") state appear to be interpretable within this framework. number of questions arising from this line of inquiry need to be addressed in the current generation of prodromal research programs: To what extent do the neural systems affected by early and late neurodevelopmental influences overlap? Is there likely to be a schizophrenia-related disturbance in the processes associated with adolescent brain maturation, or are these maturational processes themselves intact, participating in psychosis onset only indirectly, by promoting a neurobiological context in which the early neurodevelopmental disturbances can be expressed in psychotic symptoms? What pattern of changes observable from in vivo imaging studies is consistent with a reduction in neuropil volume? We develop a framework for addressing these questions and evaluating their implications for understanding the roles of early and late neurodevelopmental influences in the etiology and pathophysiology of schizophrenia. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Utrecht, Utrecht, Netherlands. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Lab Neuroimaging, Los Angeles, CA 90024 USA. Natl Publ Hlth Inst, Dept Mental Hlth, Helsinki, Finland. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Harvard Univ, Sch Med, Dept Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cannon, TD (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall, Los Angeles, CA 90095 USA. EM cannon@psych.ucla.edu NR 120 TC 160 Z9 164 U1 3 U2 15 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2003 VL 29 IS 4 BP 653 EP 669 PG 17 WC Psychiatry SC Psychiatry GA 772ZT UT WOS:000188873800004 PM 14989405 ER PT J AU Seidman, LJ Pantelis, C Keshavan, MS Faraone, SV Goldstein, JM Horton, NJ Makris, N Falkai, P Caviness, VS Tsuang, MT AF Seidman, LJ Pantelis, C Keshavan, MS Faraone, SV Goldstein, JM Horton, NJ Makris, N Falkai, P Caviness, VS Tsuang, MT TI A review and new report of medial temporal lobe dysfunction as a vulnerability indicator for schizophrenia: A magnetic resonance imaging morphometric family study of the parahippocampal gyrus SO SCHIZOPHRENIA BULLETIN LA English DT Review DE schizophrenia; relatives; genetics; MRI; hippocampus; parahippocampal gyrus; verbal declarative memory ID STRUCTURAL BRAIN ABNORMALITIES; HIPPOCAMPAL VOLUME REDUCTION; EARLY-ONSET SCHIZOPHRENIA; FIRST-DEGREE RELATIVES; ADULT HUMAN BRAIN; HIGH-RISK; NONPSYCHOTIC RELATIVES; FOLLOW-UP; 1ST-EPISODE SCHIZOPHRENIA; UNAFFECTED SIBLINGS AB A central question in schizophrenia research is which brain abnormalities are independent of psychosis and which evolve before and after psychosis begins. This question can be addressed by longitudinal neuroimaging studies beginning in the prodrome, but at present there is only one published study. We reviewed the literature on structural brain imaging in persons with chronic and first episode schizophrenia, nonpsychotic persons at genetic high risk, and persons thought to be at risk for imminent psychosis ("prodromal" persons). Medial temporal lobe (MTL), especially hippocampal, volume alterations are among the most robust brain vulnerabilities for schizophrenia. Because verbal declarative memory (VDM) deficits are prominent and the parahippocampal gyrus (PHG) is considered to be centrally involved with the hippocampus in VDM processing, we analyzed PHG data from a family study of schizophrenia. Patients with schizophrenia and nonpsychotic relatives from "multiplex" families (families with multiple persons with schizophrenia) had significantly smaller right parahippocampal anterior (PHa) volumes than controls. Marginally significant findings were observed for the left PHa. Unexpectedly, relatives from "simplex" families (families with only one person with schizophrenia) had significantly larger PH posterior volumes than controls and did not differ from controls on PHa. Results provide some support for the hypothesis that the vulnerability to schizophrenia includes abnormal volumes of the PHG. These data provide additional support for the hypothesis that some MTL abnormalities in schizophrenia are independent of psychosis, at least in families with presumably high genetic loading. Implications of genetic risk studies for prodromal research are discussed. C1 Harvard Univ, Sch Med, Commonwealth Res Ctr, Dept Psychiat,Massachussetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA 02401 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Univ Melbourne, Sunshine Hosp, Cognit Neuropsychiat Res & Acad Unit, St Albans, Vic, Australia. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat,UPMC Hlth Syst, Pittsburgh, PA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth, Boston, MA 02115 USA. Smith Coll, Dept Math, Northampton, MA 01063 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. Univ Saarland, Dept Psychiat, D-6600 Saarbrucken, Germany. Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, San Diego, CA 92103 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Seidman, LJ (reprint author), Massachusetts Mental Hlth Ctr, Commonwealth Res Ctr, 170 Morton St, Jamaica Plain, MA 02130 USA. EM larry_seidman@hms.harvard.edu RI Horton, Nicholas/A-2493-2008; Pantelis, Christos/H-7722-2014; OI Pantelis, Christos/0000-0002-9565-0238; Horton, Nicholas/0000-0003-3332-4311; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH 43518, MH 46318, MH 56956, MH 63951] NR 155 TC 98 Z9 98 U1 6 U2 9 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2003 VL 29 IS 4 BP 803 EP 830 PG 28 WC Psychiatry SC Psychiatry GA 772ZT UT WOS:000188873800015 PM 14989416 ER PT B AU Rosowski, JJ AF Rosowski, JJ BE Barth, FG Humphrey, JAC Secomb, TW TI The middle and external ears of terrestrial vertebrates as mechanical and acoustic transducers SO SENSORS AND SENSING IN BIOLOGY AND ENGINEERING LA English DT Proceedings Paper CT International Symposium on Sensors and Sensing in Natural and Fabricated World CY JUN 11-16, 2000 CL CIOCCO, ITALY SP Natl Sci Fdn, United Engn Fdn ID DOMESTIC CAT; IMPEDANCE AB The external and middle ears of terrestrial vertebrates work together to transform sound in free air to sound pressures and volume velocities in the fluid in the vestibule of the auditory inner ear. The primary structural bases for this transformation are the acoustics of the ear canal and the ratio of the areas of the tympanic membrane and the stapes footplate. The efficiency of this transformation and the extreme sensitivity of the auditory inner ear to sound enable vertebrates to hear sounds that produce sub-Angstrom displace- ments of middle-ear structures. Nonetheless, the absolute size and the form of the tympanic membrane, ossicles and ossicular suspension make the transformation process frequency selective, and it is argued that this selectivity is the primary force shaping what sounds are audible by different animal species. This chapter quantifies sound transformation through the ear of several vertebrates and discusses the structures that affect the frequency selectivity of these processes. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 35 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA BN 3-211-83771-X PY 2003 BP 59 EP 69 PG 11 WC Biology; Engineering, Biomedical; Robotics SC Life Sciences & Biomedicine - Other Topics; Engineering; Robotics GA BW84V UT WOS:000183376800005 ER PT J AU Siegel, JM AF Siegel, JM TI The narcoleptic borderland SO SLEEP MEDICINE LA English DT Editorial Material ID PLASMA OREXIN-A; HYPOCRETIN OREXIN; RELEASE C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat, VA GLAHS Sepulveda, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, VA GLAHS Sepulveda, North Hills, CA 91343 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat, VA GLAHS Sepulveda, North Hills, CA 91343 USA. EM jsiegel@ucla.edu NR 13 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JAN PY 2003 VL 4 IS 1 BP 3 EP 4 DI 10.1016/S1389-9457(02)00192-2 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 772JM UT WOS:000188838900002 PM 14592352 ER PT J AU McCowen, KC Malhotra, A AF McCowen, KC Malhotra, A TI The correlation between obstructive sleep apnea and low gonadotropin secretion in men SO SLEEP MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Malhotra, A (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. EM amalhotra1@partners.org NR 6 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JAN PY 2003 VL 4 IS 1 BP 83 EP 84 DI 10.1016/S1389-9457(02)00248-4 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 772JM UT WOS:000188838900017 ER PT J AU Jenkins, KR Fultz, NH Fonda, SJ Wray, LA AF Jenkins, KR Fultz, NH Fonda, SJ Wray, LA TI Patterns of body weight in middle-aged and older Americans, by gender and race, 1993-2000 SO SOZIAL-UND PRAVENTIVMEDIZIN LA English DT Article DE BMI; obesity; longitudinal analysis; weight change trajectories ID ALL-CAUSE MORTALITY; BLACK-AND-WHITE; UNITED-STATES; HEALTH OUTCOMES; OBESITY; OVERWEIGHT; WOMEN; TRENDS; ADULTS; GAIN AB Objectives: Despite evidence of poor health outcomes associated with excessive weight gain or loss, longitudinal patterns of body weight over the adult life course have not been fully described. This article seeks to address this by examining body weight patterns for middle-aged and older adults. Methods: Panel data from the Health and Retirement Study (HRS) original cohort and the original cohort of the Asset and Health Dynamics Among the Oldest Old (AHEAD) study are used to compare, by social group, characteristics of respondents and non-respondents, baseline weight (1993 and 1994) to year 2000 weight, and explore various weight change trajectories over time. Results: Overall, a greater proportion of middle-aged adults are heavier over time than at baseline and a greater proportion of older adults lose weight over time compared to baseline. Examining the transitions across weight trajectories for all of the social groups suggests considerable variability. Conclusions: These findings suggest that differing physiologic and social or environmental experiences may have implications for body weight patterns. Understanding these patterns by race/ethnicity and gender could provide insight into health disparities among different social groups. C1 Univ Michigan, Inst Social Res, Ann Arbor, MI 48106 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48106 USA. Penn State Univ, University Pk, PA 16802 USA. RP Jenkins, KR (reprint author), Univ Michigan, Inst Social Res, 426 Thompson St,Box 1248, Ann Arbor, MI 48106 USA. FU NIA NIH HHS [5-T32-AG00221, U01-AG09740-11] NR 32 TC 18 Z9 18 U1 2 U2 2 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 0303-8408 J9 SOZ PRAVENTIV MED JI Sozial-und Pravent. PY 2003 VL 48 IS 4 BP 257 EP 268 DI 10.1007/s00038-003-2053-3 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 715CJ UT WOS:000184952700013 PM 12971114 ER PT J AU Ke, Y Streeter, C Lowen, S Nassar, LE Parow, AM Hennen, J Yurglun-Todd, DA Sarid-Segal, O Awad, LA Rendall, M Gruber, SA Nason, A Mudrick, MJ Blank, SR Ciraulo, DA Renshaw, PF AF Ke, Y Streeter, C Lowen, S Nassar, LE Parow, AM Hennen, J Yurglun-Todd, DA Sarid-Segal, O Awad, LA Rendall, M Gruber, SA Nason, A Mudrick, MJ Blank, SR Ciraulo, DA Renshaw, PF TI Increased frontal lobe phosphocreatine levels observed in heavy cocaine users after treatment for cocaine dependence - An H-1 MRS T-2 relaxometry study SO SPECTROSCOPY-AN INTERNATIONAL JOURNAL LA English DT Article; Proceedings Paper CT 1st International Conference on Biomedical Spectroscopy CY JUL 07-10, 2002 CL CARDIFF, WALES ID MAGNETIC-RESONANCE SPECTROSCOPY; N-ACETYL ASPARTATE; HUMAN BRAIN; PHOTIC-STIMULATION; P-31-MR SPECTROSCOPY; ENERGY-METABOLISM; POLYDRUG ABUSERS; PROTON MRS; SCHIZOPHRENIA; WITHDRAWAL AB We have recently reported that relative concentrations of phosphocreatine (PCr) and creatine (Cr) may be estimated from brain 1H MR spectra based upon T-2 relaxation times. Emission tomography studies have consistently associated cocaine dependence and abstinence with decreased cerebral metabolism. We hypothesized that increased frontal lobe PCr levels would accompany treatment for cocaine dependence. Twenty-four cocaine dependent (CD) subjects were studied before and after 8 weeks of cocaine dependence treatment. Nine comparison subjects were studied at the same time points. At baseline, left frontal lobe ratios of PCr/tCr were 0.406+/-0.081 in CD subjects and 0.411+/-0.016 in comparison subjects. After treatment, these ratios increased 14.3% (0.464 vs. 0.406; p=0.006) in CD subjects, remaining unchanged in comparison subjects (2.9%, 0.399 vs. 0.411; p=0.480). At baseline, PCr levels of non-responders were 17.8% lower (0.375 vs. 0.442; p=0.042) than those of responders, defined as 25% decrease in urine cocaine metabolites. After treatment, CD subjects had increased PCr levels: 18.4% (0.444 vs. 0.375; p=0.035) for non-responders and 10.4% (0.488 vs. 0.442; p=0.092) for responders. These results are consistent with decreased cerebral metabolism during treatment, measured as increased PCr. This is the first report using H-1 MRS T-2 relaxometry to measure a change in human brain energetics. C1 Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Belmont, MA 02478 USA. Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02218 USA. NR 31 TC 2 Z9 2 U1 2 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0712-4813 J9 SPECTROSC-INT J JI Spectr.-Int. J. PY 2003 VL 17 IS 2-3 BP 231 EP 239 PG 9 WC Biochemical Research Methods; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 665MB UT WOS:000182123800012 ER PT J AU Perlingeiro, RCR Kyba, M Bodie, S Daley, GQ AF Perlingeiro, RCR Kyba, M Bodie, S Daley, GQ TI A role for thrombopoietin in hemangioblast development SO STEM CELLS LA English DT Article DE embryonic stem cells; hemangioblast; thrombopoietin; c-Mpl ID C-MPL LIGAND; HEMATOPOIETIC STEM-CELLS; BONE MORPHOGENETIC PROTEIN-4; IN-VITRO; ENDOTHELIAL-CELLS; PROGENITOR CELLS; COMMON PRECURSOR; EMBRYOS LACKING; DEFICIENT MICE; RECEPTOR AB Vascular endothelial growth factor (VEGF) and stem cell factor (SCF) act as growth factors for the hemangioblast, an embryonic progenitor of the hematopoietic and endothelial lineages. Because thrombopoietin (TPO) and its receptor, c-Mp1, regulate primitive hematopoietic populations, including bone marrow hematopoietic stem cells, we investigated whether TPO acts on the hemangioblasts that derive from differentiation of embryonic stem cells in vitro. Reverse transcriptase polymerase chain reaction analysis detected expression of c-Mp1 beginning on day 3 of embryoid body differentiation when the hemangioblast first arises. In assays of the hemangioblast colony-forming cell (BL-CFC), TPO alone supported BL-CFC formation and nearly doubled the number of BL-CFC when added together with VEGF and SCF. When replated under the appropriate conditions, TPO-stimulated BL-CFC gave rise to secondary hematopoietic colonies, as well as endothelial cells, confirming their nature as hemangioblasts. Addition of a neutralizing anti-VEGF antibody did not block TPO enhancement of BL-CFC formation, suggesting that TPO acts independently of VEGF. These results establish that Mp1 signaling plays a role in the earliest stages of hematopoietic development and that TPO represents a third growth factor influencing hemangioblast formation. C1 Whitehead Inst, Cambridge, MA 02142 USA. ViaCell Inc, Cambridge, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. RP Daley, GQ (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. OI Kyba, Michael/0000-0002-5579-7534 FU NCI NIH HHS [CA86991, CA76418]; NIDDK NIH HHS [DK59279] NR 53 TC 31 Z9 34 U1 0 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2003 VL 21 IS 3 BP 272 EP 280 DI 10.1634/stemcells.21-3-272 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 683CK UT WOS:000183129600004 PM 12743322 ER PT J AU Binder, DK Rau, G Starr, PA AF Binder, DK Rau, G Starr, PA TI Hemorrhagic complications of microelectrode-guided deep brain stimulation SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article; Proceedings Paper CT Meeting of the American-Society-for-Stereotactic-and-Functional-Neurosurgery CY MAY 18-21, 2003 CL NEW YORK, NEW YORK SP Amer Soc Stereotact & Funct Neurosurg DE hemorrhage; deep brain stimulation; microelectrode; movement disorders AB Background: The incidence of intracranial hemorrhage occurring during microelectrode-guided implantation of deep brain stimulators (DBS) for movement disorders has not been well defined. We report the incidence of hemorrhage in a large series of DBS implants into the subthalamic nucleus (STN), thalamus (VIM) and internal globus pallidus (GPi). Methods: All DBS procedures performed by a single surgeon ( P. A. S.) between June 1998 and April 2003 were included in this study. Patients had postoperative imaging (MRI or CT) 4 - 24 h following surgery, and all hematomas >0.2 cm(3) in volume were noted and scored as symptomatic ( associated with any new neurologic deficit lasting 124 h) or asymptomatic. Results: The total number of lead implants was 357. There were 5 symptomatic hematomas and 6 asymptomatic hematomas. The relative risk of hematoma ( any type) per lead implant was 3.1%. The incidence of hematoma by target site was 2.5% per lead for STN-DBS, 6.7% for GPi-DBS and 0% for VIM-DBS. Conclusion: The overall risk of intraoperative or early postoperative symptomatic hemorrhage with microelectrode-guided DBS, over all targets, was 1.4% per lead implant. The brain target had a significant effect on the risk of hemorrhage. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. RP Binder, DK (reprint author), Univ Calif San Francisco, Moffitt Hosp M779, Dept Neurol Surg, Box 0112, San Francisco, CA 94143 USA. EM dbinder@itsa.ucsf.edu NR 4 TC 68 Z9 69 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2003 VL 80 IS 1-4 BP 28 EP 31 DI 10.1159/000075156 PG 4 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 766PZ UT WOS:000188385900005 PM 14745205 ER PT J AU Rosand, J Knudsen, K Greenberg, SM AF Rosand, J Knudsen, K Greenberg, SM TI Warfarin use predicts mortality from intracerebral hemorrhage in a dose-dependent manner SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 242 EP 242 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100079 ER PT J AU Smith, EE Eng, JA Rosand, J Greenberg, SM AF Smith, EE Eng, JA Rosand, J Greenberg, SM TI Presence of leukoaraiosis predicts recurrent lobar hemorrhage SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 242 EP 242 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100082 ER PT J AU Steinberg, GK Bell-Stephens, TE Shuer, LM Ogilvy, CS Connolly, ES Solomon, R Lam, A Giannotta, S Cockroft, K Hershey, MS Dobak, J Allgren, RL AF Steinberg, GK Bell-Stephens, TE Shuer, LM Ogilvy, CS Connolly, ES Solomon, R Lam, A Giannotta, S Cockroft, K Hershey, MS Dobak, J Allgren, RL CA TCAS Study Grp TI Comparison of endovascular cooling to surface cooling during unruptured cerebral aneurysm repair SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Stanford Univ, Ctr Med, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Neurol Inst Columbia, Presbyterian Med Ctr, New York, NY USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Univ So Calif, Ctr Med, Los Angeles, CA USA. Milton S Hershey Med Ctr, Hershey, PA USA. Innercool Therapies Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 246 EP 246 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100101 ER PT J AU Krieger, DW De Georgia, MA Devlin, T Jauss, M Rordorf, G Koroshetz, WJ Davies, S AF Krieger, DW De Georgia, MA Devlin, T Jauss, M Rordorf, G Koroshetz, WJ Davies, S TI Cooling acute ischemic brain damage (COOL AID): A randomized pilot trial of endovascular cooling for patients with acute ischemic stroke SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Erlanger Clin, Chattanooga, TN USA. Univ Giessen, Giessen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Melbourne Hosp, Melbourne, Vic, Australia. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 248 EP 248 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100112 ER PT J AU Lee, SR Lo, EH AF Lee, SR Lo, EH TI Induction of caspase-mediated cell death by matrix metalloproteinase after hypoxia-reoxygenation in human brain microvascular endothelial cells SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 250 EP 250 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100122 ER PT J AU Ayata, C Ozdemir, Y Dunn, A Atochin, DN Huang, PL Muzykantov, VR Murciano, JC Boas, DA Moskowitz, MA AF Ayata, C Ozdemir, Y Dunn, A Atochin, DN Huang, PL Muzykantov, VR Murciano, JC Boas, DA Moskowitz, MA TI Laser speckle-flowmetry: A novel two-dimensional technique for the study of cerebral blood flow in normal and ischemic mouse brain, in vivo SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Penn, Sch Med, Philadelphia, PA USA. Massachusetts Gen Hosp, Charlestown, MA USA. RI Atochin, Dmitriy/Q-3150-2016 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 251 EP 251 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100128 ER PT J AU Wang, XY Arai, K Lee, SR Wang, S Pauw, RJ Rebeck, W Lo, EH AF Wang, XY Arai, K Lee, SR Wang, S Pauw, RJ Rebeck, W Lo, EH TI TPA-induced upregulation of MMP-9 in rat astrocytes and human brain endothelial cells in vitro SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 251 EP 251 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100131 ER PT J AU Kim, DE Weissleder, R Schellingerhout, D AF Kim, DE Weissleder, R Schellingerhout, D TI In vivo molecular imaging of stem cell transplantation in stroke SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 253 EP 254 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100142 ER PT J AU Schwamm, LH Bizzi, E Dyar, T Callahan, J Holden, M AF Schwamm, LH Bizzi, E Dyar, T Callahan, J Holden, M TI Training in a virtual environment improves motor recovery after stroke: A model for TeleRehabilitation SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 253 EP 253 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100138 ER PT J AU Cramer, SC Rordorf, G Maki, JH Kramer, LA Grotta, JC Burgin, WS Hinchey, JA Benesch, C Furie, KL Lutsep, HL Kelly, E Longstreth, WT AF Cramer, SC Rordorf, G Maki, JH Kramer, LA Grotta, JC Burgin, WS Hinchey, JA Benesch, C Furie, KL Lutsep, HL Kelly, E Longstreth, WT TI Paradoxical embolism from large veins in ischemic stroke (PELVIS) study SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Univ Washington, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, Houston, TX USA. Univ Rochester, Rochester, NY USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 262 EP 262 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100183 ER PT J AU Wu, O Martinos, AA Schwamm, LH Weisskoff, RM Benner, T Copen, WA Koroshetz, WJ O'Donnell, J Ostergaard, L Rosen, BR Schaefer, PW Sorensen, AG AF Wu, O Martinos, AA Schwamm, LH Weisskoff, RM Benner, T Copen, WA Koroshetz, WJ O'Donnell, J Ostergaard, L Rosen, BR Schaefer, PW Sorensen, AG TI Measuring changes in blood-brain barrier permeability with perfusion-weighted MRI in human cerebral ischemia SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 MIT, MGH, HMS Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EPIX Med, Cambridge, MA USA. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. RI Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 263 EP 263 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100188 ER PT J AU Greer, DM Lev, MH Cullen, S Gonzalez, G Koroshetz, WJ AF Greer, DM Lev, MH Cullen, S Gonzalez, G Koroshetz, WJ TI MRI improves detection of intracerebral hemorrhage over CT following intra-arterial thrombolysis SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 264 EP 264 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100196 ER PT J AU Eng, JA Frosch, MP Greenberg, SM AF Eng, JA Frosch, MP Greenberg, SM TI Cerebral amyloid angiopathy-related inflammation, subacute cognitive decline, and reversible white matter changes SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 275 EP 275 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100252 ER PT J AU Schwamm, LH Rosenthal, ES Little, EA Petkovska, I Hirshberg, A Schaefer, PW AF Schwamm, LH Rosenthal, ES Little, EA Petkovska, I Hirshberg, A Schaefer, PW TI Stroke neurologist review of brain CT via telemedicine accurately identifies candidates for IV t-PA SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Marthas Vineyard Hosp, Oak Bluffs, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 280 EP 281 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100284 ER PT J AU Schwamm, LH Moyer, P Prvu, J Labresh, KA AF Schwamm, LH Moyer, P Prvu, J Labresh, KA CA Boston Operation Stroke Study Inve TI Get with the guidelines-stroke: Acute stroke measures in patients eligible for t-PA SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston EMS, Boston, MA USA. Amer Heart Assoc, Framingham, MA USA. MassPRO Inc, Waltham, MA USA. Amer Stroke Assoc, Boston, MA USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 282 EP 282 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100293 ER PT J AU Schwamm, LH Labresh, KA Ellrodt, AG MacDonald, C Gliklich, RE AF Schwamm, LH Labresh, KA Ellrodt, AG MacDonald, C Gliklich, RE TI Get with the guidelines-stroke: Baseline data on secondary prevention SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MassPRO Inc, Waltham, MA USA. Berkshire Med Ctr, Pittsfield, MA USA. Outcome Sci Inc, Boston, MA USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 288 EP 288 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100323 ER PT J AU Wada, K Sugimori, H Bhide, PG Moskowitz, MA Finklestein, SP AF Wada, K Sugimori, H Bhide, PG Moskowitz, MA Finklestein, SP TI The effect of basic fibroblast growth factor treatment on brain progenitor cells following focal permanent ischemia in rats SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. ViaCell Inc, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 296 EP 296 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100369 ER PT J AU Tsuji, K Aoki, T Arai, K Tsirka, S Lo, EH AF Tsuji, K Aoki, T Arai, K Tsirka, S Lo, EH TI Tissue plasminogen activator triggers matrix metalloproteinase-9 upregulation after cerebral ischemia: Pharmacologic and genetic studies SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 297 EP 298 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100376 ER PT J AU Arai, K Lee, SR Lo, EH AF Arai, K Lee, SR Lo, EH TI Essential role for ERK MAP kinase in matrix metalloproteinase-9 regulation in rat cortical astrocytes SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 298 EP 298 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100378 ER PT J AU Lee, SR Lo, EH AF Lee, SR Lo, EH TI Efficacy of MAP kinase inhibitors against hypoxia-reoxygenation induced cytotoxicity in human brain microvascular endothelial cells SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 299 EP 299 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100386 ER PT J AU Ickenstein, GW Ambrosi, D Rallis, N Goldstein, R Stein, J AF Ickenstein, GW Ambrosi, D Rallis, N Goldstein, R Stein, J TI Predictors of mortality in stroke patients with dysphagia SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Spaulding Rehabil Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 317 EP 317 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100482 ER PT J AU Schwamm, LH Hochberg, LR Petkovska, I Sokal, S Furie, KL Hylek, EM Little, EA Gleason, S AF Schwamm, LH Hochberg, LR Petkovska, I Sokal, S Furie, KL Hylek, EM Little, EA Gleason, S TI Web-enabled decision support improves anticoagulation management in hospitalized patients with stroke/TIA SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 322 EP 322 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100509 ER PT J AU Simpson, TL AF Simpson, TL TI Childhood sexual abuse, PTSD, and the functional roles of alcohol use among women drinkers SO SUBSTANCE USE & MISUSE LA English DT Article DE human females; drinking behavior; sexual abuse; posttraumatic stress disorder; alcohol-related expectancies ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE DISORDERS; PERSONALITY-VARIABLES; SELF-MEDICATION; DRUG-ABUSE; VICTIMIZATION; COMORBIDITY; ADOLESCENT; DEPENDENCE; DRINKING AB The present study investigated whether a history of childhood sexual abuse (CSA) or current post traumatic stress disorder (PTSD) was associated with alcohol-related expectancies and recalled effects of drinking reported by women in substance user treatment. The results indicate that CSA status was not associated with the alcohol-related expectancies or effects of drinking reported by women in substance user treatment. However, those currently manifesting PTSD were more likely than their peers without PTSD to report greater alcohol-related expectancies of tension reduction and having experienced greater positive enhancement from drinking. Theoretical and clinical implications of these findings are considered. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Washington, DC USA. RP Simpson, TL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,116-MHC, Seattle, WA 98108 USA. FU NIAAA NIH HHS [5 R01 AA09774, T32 AA07455-17, T32 AA07460-10] NR 70 TC 29 Z9 29 U1 7 U2 18 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PD JAN PY 2003 VL 38 IS 2 BP 249 EP 270 DI 10.1081/JA-120017248 PG 22 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 645AR UT WOS:000180954500005 PM 12625430 ER PT J AU Gordon, AJ Conigliaro, J Maisto, SA McNeil, M Kraemer, KL Kelley, ME AF Gordon, AJ Conigliaro, J Maisto, SA McNeil, M Kraemer, KL Kelley, ME TI Comparison of consumption effects of brief interventions for hazardous drinking elderly SO SUBSTANCE USE & MISUSE LA English DT Article DE alcohol drinking; counseling; aged; randomized controlled trial; early interventions; hazardous drinking ID PRIMARY-CARE PATIENTS; ALCOHOLISM SCREENING QUESTIONNAIRES; RANDOMIZED CONTROLLED TRIAL; BRIEF PHYSICIAN ADVICE; OLDER ADULTS; USE DISORDERS; FOLLOW-UP; DRINKERS; IDENTIFICATION; POPULATION AB We sought to determine if Brief Interventions [BIs, Motivational Enhancement (ME), and Brief Advice (BA)] reduced alcohol consumption among hazardous alcohol drinking elderly (65 years or older) and whether the elderly responded similarly to younger populations. In 12 primary care offices from October 1995 to December 1997, we screened 13,438 patients of whom 2702 were elderly (180 were hazardous drinkers). Forty-five elderly enrollees were randomized to receive ME (n = 18), BA (n = 12), and Standard Care (SC, n = 12). At baseline, the elderly drank more alcohol and abstained fewer days than the younger cohort (p < 0.05). During the year, the elderly in ME, BA, and SC intervention arms increased the number of days abstained, decreased the number of drinks per day, and reduced the number of total days per month drinking. There were trends toward decreases in the alcohol consumption measures in the ME and BA treatment arms compared to SC. The elderly's response to all interventions was similar to that of the younger cohort. This study suggests that hazardous alcohol consumption in the elderly is common and that BIs reduce alcohol consumption in the elderly similar to younger populations. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Gen Internal Med Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA USA. Syracuse Univ, Ctr Hlth & Behav, Dept Psychol, Syracuse, NY USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Gen Internal Med Sect, 130-U,Room 11E-118-U,Univ Dr C, Pittsburgh, PA 15240 USA. FU NIAAA NIH HHS [AA10291, AA00235] NR 45 TC 29 Z9 30 U1 5 U2 7 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2003 VL 38 IS 8 BP 1017 EP 1035 DI 10.1081/JA-120017649 PG 19 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 705EY UT WOS:000184383800001 PM 12901447 ER PT J AU Shimada, H Germana, S Hayashi, H Sachs, DH LeGuern, C AF Shimada, H Germana, S Hayashi, H Sachs, DH LeGuern, C TI Expression of MHC class II DQ alpha/beta heterodimers from recombinant polycistronic retroviral genomes SO SURGERY TODAY LA English DT Article DE polycistronic retroviral vector; MHC class II gene; transplantation tolerance; molecular chimerism ID BONE-MARROW CELLS; MINIATURE SWINE; GENE-TRANSFER; REVERSE TRANSCRIPTION; MEDIATED TRANSFER; RENAL-ALLOGRAFTS; VECTORS; TOLERANCE; THERAPY; ENTRY AB Purpose. In the swine model, the transfer of the polymorphic DRbeta or DQalpha/beta cDNAs in vivo via double copy retroviruses led to a prolonged survival or tolerance of subsequent kidney grafts which were matched for DR or DQ, respectively. However, DQ-induced tolerance required the expression of the alpha/beta heterodimers in the same target cell, a task not reproducibly achieved with double copy vectors. Therefore, the present study was designed to evaluate the ability of polycistronic proviral constructs to express class 11 DQ alpha/beta heterodimers in transduced cells. Methods. A swine class 11 DQ recombinant polycistronic construct (JAB) was developed to contain two internal ribosomal entry sites (IRES) for sequential translation of the DQalpha and DQbeta chains. Results. Although a genomic recombination occurred between the two identical IRES, flow cytometry analyses of JAB-transfected virus-packaging cells demonstrated the cell surface expression of DQalpha/DQbeta heterodimers, indicative of a correct transcription, translation, and transport of swine class II. Conclusion. JAB-transfected virus-packaging cells demonstrated the cell surface expression of DQalpha/DQbeta heterodimers. We believe that our study represents an essential step in the design of efficient protocols to transfer graft-matched class 11 molecules in recipient bone marrow cells and thereby induce transplantation tolerance. C1 Chiba Univ, Grad Sch Med, Acad Dept Surg, Chiba 2608677, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Shimada, H (reprint author), Chiba Univ, Grad Sch Med, Acad Dept Surg, 1-8-1 Inohana, Chiba 2608677, Japan. FU NIAID NIH HHS [2R01AI33053] NR 37 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-1291 J9 SURG TODAY JI Surg. Today PY 2003 VL 33 IS 3 BP 183 EP 189 PG 7 WC Surgery SC Surgery GA 665ZV UT WOS:000182151900004 PM 12658383 ER PT J AU Watkins, LM Janfaza, P Rubin, PAD AF Watkins, LM Janfaza, P Rubin, PAD TI The evolution of endonasal dacryocystorhinostomy SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE conjunctivodacryocystorhinostomy; dacryocystography; dacryocystorhinostomy; endoscopy; hemostasis; laser; middle turbinate; osteomy; stents; uncinate process ID LASER-ASSISTED DACRYOCYSTORHINOSTOMY; NASOLACRIMAL DUCT OBSTRUCTION; ENDOSCOPIC TRANSNASAL DACRYOCYSTORHINOSTOMY; UNSUCCESSFUL LACRIMAL SURGERY; MITOMYCIN-C; EXTERNAL DACRYOCYSTORHINOSTOMY; PEDIATRIC DACRYOCYSTORHINOSTOMY; CRAWFORD TUBES; JONES TUBE; MANAGEMENT AB Dacryocystorhinostomy is an important treatment in the relief of tearing. Through the years, there have been several advances in this procedure. Once performed only from an external approach, the advent of rigid endoscopes and endoscopic instrumentation has made the endonasal approach a reality. Advantages of the endonasal approach include lack of a cutaneous incision and excellent visualization of intranasal pathology, which is often the cause of dacryocystorhinostomy failure. Preoperative evaluation including a detailed medical history, physical examination with office endoscopy, and imaging, as well as postoperative care are important. Surgical technique with detailed knowledge of intranasal anatomy and meticulous attention to hemostasis are critical. Endonasal laser-assisted dacryocystorhinostomy is also performed today, and special preoperative considerations and key features of the lasers available are important in the selection of a laser for tissue or bone ablation during the procedure. Endoscopic conjunctivodacryocystorhinostomy), is performed today, and given the critical nature of proper length and placement of the Jones tube intranasally, provides the significant advantage of intranasal visualization. Endoscopic dacryocystorhinostomy in children is also performed today; however, challenges such as small nasal anatomy and maintenance of the intranasal osteomy postoperatively in a child are significant issues. (C) 2003 by Elsevier Science Inc. All rights reserved. C1 Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. RI wei, chi/H-5730-2011 NR 99 TC 66 Z9 72 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JAN-FEB PY 2003 VL 48 IS 1 BP 73 EP 84 AR PII S0039-6257(02)00397-1 DI 10.1016/S0039-6257(02)00397-1 PG 12 WC Ophthalmology SC Ophthalmology GA 637XK UT WOS:000180538900005 PM 12559328 ER PT J AU Chen, CC Loeffler, JS Chapman, PH AF Chen, CC Loeffler, JS Chapman, PH TI Proton beam radiosurgery and radiotherapy SO TECHNIQUES IN NEUROSURGERY LA English DT Article DE radiotherapy; radiosurgery; proton irradiation; high-dose radiation; treatment planning ID SKULL BASE MENINGIOMAS; RELATIVE BIOLOGICAL EFFECTIVENESS; RADIATION-THERAPY; ARTERIOVENOUS-MALFORMATIONS; STEREOTAXIC RADIOSURGERY; ACOUSTIC NEUROMA; CEREBELLAR MEDULLOBLASTOMA; CONFORMAL RADIOTHERAPY; VESTIBULAR SCHWANNOMAS; PRELIMINARY EXPERIENCE AB In contrast to photon irradiation, where energy deposition is distributed over a relatively large area, the physical properties of proton irradiation are such that energy deposition occurs within a small target volume. As such, proton beams represent a new platform on which specific delivery of high-dose radiation can be achieved with minimal disruption of normal tissues. Since our understanding of the radiobiology of proton radiation remains incomplete, proton beam treatment planning is based on empirical estimates of tissue effects. Despite such limitations, notable successes have been achieved in the treatment of uveal melanomas, chondrosarcomas, meningiomas, acoustic neuromas, arteriovenous malformations, malignant gliomas, and medulloblastomas. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chapman, PH (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, GRB 5-502,55 Fruit St, Boston, MA 02114 USA. NR 71 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-2855 J9 TECH NEUROSURG JI Tech. Neurosurg. PY 2003 VL 9 IS 3 BP 218 EP 225 DI 10.1097/00127927-200309030-00014 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 747YH UT WOS:000186833600014 ER PT J AU Shklovsky-Kordi, NE Zingerman, BV Goldberg, SV Velichko, SA Gudilina, YY Kaplanov, KD Klimenko, SV Kravchenko, SK Kremenetskaya, AM Kobelyatsky, VF Kostochkina, SV Margolin, OV Rivkind, NB Freidin, YL Erlikh, LI Vorobyev, AI AF Shklovsky-Kordi, NE Zingerman, BV Goldberg, SV Velichko, SA Gudilina, YY Kaplanov, KD Klimenko, SV Kravchenko, SK Kremenetskaya, AM Kobelyatsky, VF Kostochkina, SV Margolin, OV Rivkind, NB Freidin, YL Erlikh, LI Vorobyev, AI TI Computer multimedia case history as a present-day tool of keeping records SO TERAPEVTICHESKII ARKHIV LA Russian DT Article DE computer case history; protocols of patient's management; prevention of medical errors; telemedicine AB Aim. To design the program of computer multimedia case history (MCH) for collection, storage and analysis of information about the patient including diagnostic images; to test MCH for application in telemedical consulting and control over valid conduction of the treatment protocol. Material and methods. Brief representation of information is reached by integrated multilevel placement of the data on common time axis. Dynamics of the selected parameters is represented as normalized diagrams in the same system axes. Electron tables are filled either by hand or import of the data from individual electron file of all the information about the patient. Diagnostic images and conclusions are obtained from local computer bases of the diagnostic units. Inexpensive commonly used computers allows one to input digital micro- and macrophotos, x-ray images, etc. Monitor information is available from the universal computer net directly from the monitors Geolink-M. Results. MCH was tested in the Hematological Research Center of RAMS. In cooperation with Bryansk diagnostic center N 1 telemedical consulting and some data bases were perfected. The MCH system joints routine activity of the clinic without any problems raising quality of the patients management, facilitating the access to therapeutic and diagnostic information and its analysis. On-line breaking the limits of the controlled parameters and protocols is detected automatically. These events are emphasized by "blocking questions" which must be worked out by the user. The information on the patient can be filly stored on CD-ROM in line with the MCH program providing organization of the data. Conclusion. The system is introduced which collects medical information from various sourses and builds up comprehensive representation of the data on the same time axis. The system provides control over implimintation of the protocols of the patients' management, gives a convenient access to medical information, ensures its reliable storage and availability in case of the patients transfer to other medical institutions, facilitates analysis of clinical cases, conduction of medical consulting. C1 Russian Acad Med Sci, Hematol Res Ctr, Moscow, Russia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Russian Acad Sci, Inst High Energy Phys, Protvino, Russia. Bryansk Diagnost Ctr, Bryansk, Russia. RP Russian Acad Med Sci, Hematol Res Ctr, Moscow, Russia. OI Kravchenko, Sergey/0000-0001-9086-8521 NR 11 TC 0 Z9 0 U1 0 U2 0 PU IZDATELSTVO MEDITSINA PI MOSCOW PA PETROVERIGSKII PER 6-8, K-142 MOSCOW, RUSSIA SN 0040-3660 J9 TERAPEVT ARKH JI Ter. Arkhiv PY 2003 VL 75 IS 7 BP 73 EP + PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 739EV UT WOS:000186331200014 PM 12934486 ER PT J AU Saw, J Kereiakes, DJ Mahaffey, KW Applegate, RJ Braden, GA Brent, BN Brodie, BR Groce, JB Levine, GN Leya, F Moliterno, DJ AF Saw, J Kereiakes, DJ Mahaffey, KW Applegate, RJ Braden, GA Brent, BN Brodie, BR Groce, JB Levine, GN Leya, F Moliterno, DJ TI Evaluation of a novel point-of-care enoxaparin monitor with central laboratory anti-Xa levels SO THROMBOSIS RESEARCH LA English DT Article DE anti-Xa activity; clotting time; enoxaparin ID PERCUTANEOUS CORONARY INTERVENTION; MOLECULAR-WEIGHT HEPARIN; UNFRACTIONATED HEPARIN; SUBCUTANEOUS ENOXAPARIN; UNSTABLE ANGINA; COMBINATION; ABCIXIMAB; TRIAL; EFFICACY; SAFETY AB Background: Measurement of enoxaparin's anticoagulant activity has been limited to specialized coagulation laboratories and has been impractical for areas needing rapid results, such as during coronary angioplasty. A new point-of-care device, Rapidpoint(R) ENOX(R), was recently developed to measure clotting times with enoxaparin use. Objectives: To correlate ENOX times with anti-Xa levels among patients receiving enoxaparin. Methods: A total of 166 patients receiving enoxaparin for the prevention of deep venous thrombosis or as treatment during acute coronary syndromes or angioplasty were prospectively studied. Ciliated and non-citrated whole-blood (CWB and NCWB) samples were obtained at baseline and peak enoxaparin activity. ENOX times were measured with whole-blood, and the Stachrom(R) anti-Xa assay was performed on the plasma from the remainder of the samples. The Pearson correlation coefficient was used to assess the relationship between these two assays. Results: There was a strong linear correlation between the ENOX times and the anti-Xa activities for both CWB (r = 0.89, p<0.001) and NCWB (r=0.82, p<0.001) when considering all 332 samples (baseline and peak). When baseline samples were excluded, the correlation remained strong for CWB ENOX times and anti-Xa levels (r = 0.84, p<0.001), but was only moderate for NCWB (r = 0.73, p<0.001). A CWB ENOX time of less than or equal to 160 s corresponded to anti-Xa level of less than or equal to 0.5 IU/ml in 95% (188/197) of patients. A CWB ENOX time greater than or equal to 200 s corresponded to anti-Xa levels greater than or equal to 0.8 IU/ml in 96% (93/96) of patients. Conclusions: Rapidpoint(R) ENOX times correlate strongly to anti-Xa activities measured by the Stachrom(R) Heparin Assays for citrated whole-blood samples. This novel test can be used for rapid bedside measurements of enoxaparin anticoagulant activity. (C) 2004 Elsevier Ltd. All rights reserved. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Ohio Heart Hlth Ctr, Linder Ctr, Cleveland, OH 44195 USA. Duke Clin Res Inst, Div Cardiovasc Med, Durham, NC USA. Wake Forest Univ, Med Ctr, Div Cardiovasc Med, Winston Salem, NC 27109 USA. Forsythe Med Ctr, Winston Salem, NC USA. Calif Pacific Med Ctr, Geraldine Brush Canc Res Inst, San Francisco, CA USA. Moses Cone Hosp, Greensboro, NC USA. Houston VAMC, Div Cardiovasc Med, Houston, TX USA. Loyola Univ, Med Ctr, Div Cardiovasc Med, Maywood, IL 60153 USA. Univ Kentucky, Gill Heart Inst, Lexington, KY 40536 USA. Univ Kentucky, Div Cardiovasc Med, Lexington, KY 40536 USA. RP Moliterno, DJ (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM moliterno@uky.edu NR 21 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2003 VL 112 IS 5-6 BP 301 EP 306 DI 10.1016/j.thromres.2004.01.006 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 808VD UT WOS:000220595700008 PM 15041274 ER PT B AU Brewster, DC AF Brewster, DC BE Pearce, WH Matsumura, JS Yao, JST TI Will endovascular aneurysm repair survive the test of time? SO TRENDS IN VASCULAR SURGERY LA English DT Proceedings Paper CT Annual Northwestern Vascular Symposium CY DEC 12-14, 2002 CL CHICAGO, IL ID ABDOMINAL AORTIC-ANEURYSM; STENT-GRAFT TREATMENT; LIFE TABLE METHOD; MULTICENTER; MIDTERM; COMPLICATIONS; EXPERIENCE; ENDOGRAFT; INTERMEDIATE; EUROSTAR C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Brewster, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU PRECEPT PRESS INC PI CHICAGO PA 160 E ILLINOIS ST, CHICAGO, IL 60611 USA BN 0-944496-70-9 PY 2003 BP 163 EP 169 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA BX60H UT WOS:000185823500017 ER PT S AU Kuipers, S Aerts, PC Cluysenaer, OJJ Bartelink, AKM Ezekowitz, RAB Bax, WA Salimans, M Vandyk, H AF Kuipers, S Aerts, PC Cluysenaer, OJJ Bartelink, AKM Ezekowitz, RAB Bax, WA Salimans, M Vandyk, H BE Marzuki, S Verhoef, J Snippe, H TI A case of familial meningococcal disease due to deficiency in mannose-binding lectin (MBL) SO TROPICAL DISEASES: FROM MOLECULE TO BEDSIDE SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 2nd International Eijkman Symposium on Tropical Diseases CY SEP 02-06, 2001 CL BOGOR, INDONESIA C1 Univ Utrecht, Ctr Med, Eijkman Winkler Ctr Microbiol Infect Dis & Inflam, Utrecht, Netherlands. Meander Med Ctr, Dept Internal Med, Amersfoort, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Kuipers, S (reprint author), Univ Utrecht, Ctr Med, Eijkman Winkler Ctr Microbiol Infect Dis & Inflam, Utrecht, Netherlands. NR 3 TC 14 Z9 15 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47799-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 531 BP 351 EP 355 PG 5 WC Genetics & Heredity; Public, Environmental & Occupational Health; Infectious Diseases; Medicine, Research & Experimental SC Genetics & Heredity; Public, Environmental & Occupational Health; Infectious Diseases; Research & Experimental Medicine GA BX17A UT WOS:000184498000029 PM 12916805 ER PT B AU Oliva, E AF Oliva, E BE Vizjak, A Ferluga, D Bussolati, G TI Endometriallioid stromal tumors: diagnostic problems at extrauterine sites with emphasis on recent immunohistochemical developments SO UPDATE IN PATHOLOGY, PROCEEDINGS LA English DT Proceedings Paper CT 19th European Congress of Pathology CY SEP 06-11, 2003 CL Ljubljana, SLOVENIA ID MULLERIAN-INHIBITING SUBSTANCE; DIFFERENTIAL-DIAGNOSIS; MONOCLONAL-ANTIBODY; OVARIAN-TUMORS; CELL CARCINOMA; ALPHA-INHIBIN; EXPRESSION; NEOPLASMS; SARCOMAS; UTERUS C1 Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Oliva, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU UNIV LJUBLJANA, PI LJUBLJANA PA FACULTY MEDICINE, INST PATHOLOGY, LJUBLJANA, 00000, SLOVENIA BN 961-6264-48-6 PY 2003 BP 119 EP 122 PG 4 WC Pathology SC Pathology GA BAV70 UT WOS:000223822500055 ER PT J AU Talcott, JA AF Talcott, JA TI What patients should be told before agreeing to a blood test that could change their lives SO UROLOGY LA English DT Editorial Material ID PROSTATE-SPECIFIC ANTIGEN; CANCER MORTALITY; TRENDS; BIOPSY; TRIAL C1 Massachusetts Gen Hosp, Ctr Outcomes Res, MGH Canc Ctr, Boston, MA 02114 USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Outcomes Res, MGH Canc Ctr, E00 3C,55 Fruit St, Boston, MA 02114 USA. NR 25 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2003 VL 61 IS 1 BP 7 EP 9 AR PII S0090-4295(02)02148-9 DI 10.1016/S0090-4295(02)02148-9 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 642BY UT WOS:000180785500003 PM 12559254 ER PT J AU Smith, MR Fallon, MA Goode, MJ AF Smith, MR Fallon, MA Goode, MJ TI Cross-sectional study of bone turnover during bicalutamide monotherapy for prostate cancer SO UROLOGY LA English DT Article ID SEX STEROID-LEVELS; MINERAL DENSITY; HORMONE AGONISTS; AROMATASE DEFICIENCY; RANCHO BERNARDO; HIP FRACTURE; OLDER MEN; FOLLOW-UP; 150 MG; WOMEN AB Objectives. Monotherapy with bicalutamicle increases serum concentrations of testosterone and estradiol. Because estrogens play an important role in male bone metabolism, bicalutamicle monotherapy may have fewer adverse effects on bone than androgen-deprivation therapy with a gonaclotropin-releasing hormone agonist. Methods. In a cross-sectional study, we compared gonadal steroid levels and biochemical markers of bone turnover among three groups of men with prostate cancer: hormone-naive men, men treated with a gonaclotropin-releasing hormone agonist, and men receiving bicalutamicle monotherapy. Men with bone metastases or metabolic bone disease were excluded. Fifty-five eligible subjects were included in the analyses. Results. Serum testosterone and estradiol concentrations were lower in men treated with a gonaclotropin-releasing hormone agonist than in hormone-naive men or men receiving bicalutamide monotherapy (P <0.001 for each comparison). Serum testosterone and estradiol concentrations were higher in men receiving bicalutamicle monotherapy than in the hormone-naive men (P <0.001). The mean serum urinary excretion of deoxypyridinoline, urinary excretion of N-telopepticle, and serum osteocalcin were significantly higher in men treated with a gonaclotropin-releasing hormone agonist than in the other groups (P <0.05 for each comparison). In contrast, biochemical markers of bone turnover were similar for hormone-naive men and men receiving bicalutamicle monotherapy (P >0.05 for each comparison). Conclusions. Biochemical markers of bone turnover are elevated in men receiving gonaclotropin-releasing hormone agonist treatment but not in men receiving bicalutamicle monotherapy. These observations suggest that bicalutamide monotherapy may maintain bone mineral density and prevent fractures. UROLOGY 61: 127-131, 2003. © 2003, Elsevier Science Inc. C1 Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Cox Bldg,Rm 640,100 Blossom St, Boston, MA 02114 USA. NR 31 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2003 VL 61 IS 1 BP 127 EP 131 AR PII S0090-4295(02)02006-X DI 10.1016/S0090-4295(02)02006-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 642BY UT WOS:000180785500031 PM 12559282 ER PT J AU Datta, MW Hosenpud, J Osipov, V Young, RH AF Datta, MW Hosenpud, J Osipov, V Young, RH TI Giant multilocular cystadenoma of the prostate responsive to GnRH antagonists SO UROLOGY LA English DT Article AB Giant multilocular cystadenoma of the prostate is a rare, benign, but locally recurrent, tumor that is usually treated by surgery. We report a case initially treated by surgical resection and followed by evaluation of serum prostate-specific antigen values. After evidence of biochemical failure, pathologic recurrence was confirmed and treated by the gonadotropin-releasing hormone antagonist Lupron, with excellent results. The patient was stable without biochemical or radiologic evidence of progression during the last 2.5 years. This result offers a new treatment option for patients with this rare tumor. (C) 2003, Elsevier Science Inc. C1 Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Datta, MW (reprint author), Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2003 VL 61 IS 1 AR PII S0090-4295(02)02109-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 642BY UT WOS:000180785500061 ER PT J AU Iezzoni, LI McCarthy, EP Davis, RB Siebens, H AF Iezzoni, Lisa I. McCarthy, Ellen P. Davis, Roger B. Siebens, Hilary BE Altman, BM Barnartt, SN Hendershot, GE Larson, SA TI ACCESS TO HEALTH CARE AND INSURANCE FOR WORKING-AGE ADULTS REPORTING MOBILITY DIFFICULTIES SO USING SURVEY DATA TO STUDY DISABILITY: RESULTS FROM THE NATIONAL HEALTH SURVEY ON DISABILITY SE Research in Social Science and Disability LA English DT Article; Book Chapter ID PREVENTIVE SERVICES; MEDICARE BENEFICIARIES; FUNCTIONAL DISABILITY; PHYSICAL-DISABILITIES; AMBULATORY PATIENTS; GAIT DISORDERS; MANAGED CARE; SATISFACTION; PROFILE AB Persons with disabilities can experience problems obtaining health care. Using the 1994-1995 National Health Interview Survey disability supplement, we examined health insurance coverage and access to health services for working-age adults with mobility problems (difficulty walking, climbing stairs, standing): 6.1% (estimated 9.48 million) of persons 18-64 years old. People reporting minor and moderate mobility difficulties had slightly lower health insurance rates than those without mobility problems (around 76% compared to almost 80%). People with mobility difficulties were more likely than others to be denied coverage and to cite pre-existing health conditions as the reason. C1 [Iezzoni, Lisa I.; Siebens, Hilary] Harvard Univ, Sch Med, Dept Phys Med & Rehabil PMR, Cambridge, MA 02138 USA. [Iezzoni, Lisa I.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Siebens, Hilary] Massachusetts Gen Hosp, PMR Serv, Boston, MA 02114 USA. [Davis, Roger B.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Iezzoni, LI (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil PMR, Cambridge, MA 02138 USA. NR 57 TC 2 Z9 2 U1 2 U2 2 PU EMERALD GROUP PUBLISHING LIMITED PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY, W YORKSHIRE BD16 1WA, ENGLAND BN 978-0-7623-1007-4 J9 RES SOC SCI DISABIL PY 2003 VL 3 BP 131 EP 155 DI 10.1016/S1479-3547(03)03008-2 PG 25 WC Rehabilitation; Social Sciences, Interdisciplinary; Sociology SC Rehabilitation; Social Sciences - Other Topics; Sociology GA BOH58 UT WOS:000276666300008 ER PT J AU Dzik, WH Murphy, MF Andreu, G Heddle, N Hogman, C Kekomaki, R Murphy, S Shimizu, M Smit-Sibinga, CT AF Dzik, WH Murphy, MF Andreu, G Heddle, N Hogman, C Kekomaki, R Murphy, S Shimizu, M Smit-Sibinga, CT TI An international study of the performance of sample collection from patients SO VOX SANGUINIS LA English DT Article DE error rates; patient safety; sample collection; standards ID NEW-YORK-STATE; TRANSFUSION ERRORS AB Background and Objectives Collection of a blood sample from the correct patient is the first step in the process of safe transfusion. The aim of this international collaborative study was to assess the frequency of mislabelled and miscollected samples drawn for blood grouping. Materials and Methods Hospitals in 10 countries provided data on sample error rates during a period of at least 3 months, including the last quarter of 2001. Mislabelled samples were defined as those not meeting local criteria for acceptance by the laboratory. Miscollected samples [wrong-blood-in-tube (WBIT)] were defined as samples in which the blood group result differed from the result on file from prior testing. WBIT rates were corrected for the proportion of repeat samples and for undetectable errors occurring as a result of chance collection of blood from the wrong patient with the same ABO group. Participants also completed a questionnaire on current policies regarding sample collection. Results A total of 71 hospitals completed surveys describing policies related to sample collection. Sixty-two hospitals provided usable data on the frequency of mislabelled and miscollected samples. Mislabelled and miscollected samples were common. Based on results from over 690 000 samples, the median hospital performance resulted in a rate for mislabelling of 1 in every 165 samples (6.1 per 1000; interquartile range 1.2-17 per 1000). The presence of national patient identification systems in Sweden and Finland was associated with rates of miscollected samples that were too low to estimate. Outside these nations, miscollected samples demonstrating WBIT occurred at a median rate of 1 in every 1986 samples (0.5 per 1000; interquartile range < 0.3-0.9 per 1000). There was great variation worldwide in the reported frequency of mislabelled samples, probably resulting from variation in policies for sample acceptance. Miscollected samples occurred at a more constant rate. Conclusions The rate of mislabelled samples and miscollected samples is 1000-10 000-fold more frequent than the risk of viral infection. Rates of mislabelled samples and WBIT can be tracked as key indicators of performance of an important step in the clinical transfusion process. WBIT episodes represent important 'near-miss' errors. By providing baseline performance data for the collection of patient blood samples, this study may be useful in formulating future national standards of performance for sample collection from patients. C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, WH (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. RI Selogie, Eileen/L-3628-2016 NR 10 TC 76 Z9 80 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2003 VL 85 IS 1 BP 40 EP 47 DI 10.1046/j.1423-0410.2003.00313.x PG 8 WC Hematology SC Hematology GA 694VA UT WOS:000183794700006 PM 12823729 ER PT J AU Ouimette, P Wolfe, J Daley, J Gima, K AF Ouimette, P Wolfe, J Daley, J Gima, K TI Use of VA health care services by women veterans: Findings from a national sample SO WOMEN & HEALTH LA English DT Article DE women veterans; health service use; trauma; Department of Veterans Affairs (DVA) ID FEMALE VETERANS; SEXUAL ASSAULT; MEDICAL-CARE; AFFAIRS; VICTIMIZATION; MILITARY; SYSTEM; ACCESS AB The Department of Veterans Affairs (VA) has a Congressional mandate but few empirical data on which to design and improve national health care services for women. We examined characteristics associated with women's current, former and non-use of the VA health care system. The study included 1,500 female veterans sampled from the Department of Veterans Affairs National Registry of Women Veterans. Women completed a 45-minute telephone survey assessing multiple domains of functional status and health service use. Using multivariate logistic regression, use of VA health care was associated with older age, more education, not being married, lower rates of insurance coverage, and poorer physical and psychological health. Women who were former users of VA health care were more likely to be ethnic minorities, have children, served less time in the military, had higher rates of insurance coverage and better physical and psychological health than current users. Prominent military experiences (e.g., service in a war-zone, exposure to trauma) were associated with former use and never using the VA health care system. Women who use VA health care are at greater economic, social, and health risk than nonusers, factors that have personal implications for the veteran as well as cost and service implications for VA. Additional research is needed to better understand the role of military experiences in women veterans' choice of health care. (C) 2003 by The Haworth Press, Inc. All rights reserved. C1 Washington State Univ, Washington Inst Mental Illness Res & Training, Spokane, WA USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. MGH Partners Hlth Care Syst, Boston, MA USA. Behav Risk Anal, San Mateo, CA USA. RP Ouimette, P (reprint author), 720 ED St, Moscow, ID 83843 USA. NR 25 TC 28 Z9 28 U1 2 U2 4 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2003 VL 38 IS 2 BP 77 EP 91 DI 10.1300/J013v38n02_06 PG 15 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 751QY UT WOS:000187079500006 PM 14655796 ER PT J AU Hoffschmidt, SJ Weinstein, CS AF Hoffschmidt, SJ Weinstein, CS TI The influence of silent learning disorders on the lives of women SO WOMEN & THERAPY LA English DT Article DE learning disorders; undiagnosed learning disorders; women AB Longstanding neurocognitive deficits such as learning disorders greatly influence development of a woman's personality, relationships, and educational and vocational attainment. In our clinical practice, we increasingly see women with previously undiagnosed "silent learning disorders." Educational and career milestones, problems in the workplace, parenting a child with a learning disorder, and normal aging along with common medical conditions can exacerbate these "silent learning disorders." As a result, neurocognitive deficits might appear more pronounced as former ways of compensating for learning problems no longer are adequate. When such learning disorders are not detected, women and their therapists might not avail themselves of interventions that can help to treat the reading, visual-spatial, organizational, or other neurocognitive deficits, and indirectly help with patterns of anxiety, depression, and low self-esteem. In the present paper, we characterize women with silent learning disorders, discuss implications if disorders remain undetected, and present case examples. A model and strategies for detecting silent learning disorders also are presented. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Hosp, Boston, MA USA. BIDMC, Boston, MA USA. RP Hoffschmidt, SJ (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0270-3149 J9 WOMEN THER JI Women Ther. PY 2003 VL 26 IS 1-2 BP 81 EP 94 PG 14 WC Psychology, Multidisciplinary; Women's Studies SC Psychology; Women's Studies GA 689YK UT WOS:000183520400007 ER PT J AU Cooper, DKC AF Cooper, DKC TI 6th Congress of the International Xenotransplantation Association SO XENOTRANSPLANTATION LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2003 VL 10 IS 1 BP 7 EP 9 DI 10.1034/j.1399-3089.2003.02002.x PG 3 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 636UH UT WOS:000180475300002 PM 12535220 ER PT J AU Rodriguez-Barbosa, JI Zhao, Y Houser, S Zhao, GL Sykes, M AF Rodriguez-Barbosa, JI Zhao, Y Houser, S Zhao, GL Sykes, M TI Fetal porcine thymus engraftment, survival and CD4 reconstitution in alpha Gal-KO mice is impaired in the presence of high levels of antibodies against alpha Gal SO XENOTRANSPLANTATION LA English DT Article DE alpha Gal-KO; fetal porcine thymus; natural antibodies; tolerance ID DELAYED XENOGRAFT REJECTION; DONOR-SPECIFIC TOLERANCE; SKIN-GRAFT TOLERANCE; T-CELL; MIXED CHIMERISM; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; XENOGENEIC TRANSPLANTATION; NATURAL ANTIBODIES; GALACTOSYL EPITOPES; THYMECTOMIZED MICE AB Xenospecific T-cell tolerance can be induced among murine and human T-cells by porcine thymic grafting. However, anti-alpha 1,3-galactosyltranserase (alphaGal) (Galalpha1-3Galbeta1-4GlcNAc-R) natural antibodies (NAbs) pose a major barrier to porcine xenografts in humans. We used alphaGal knockout (KO) and mu chain KO mice to explore the effect of natural anti-alphaGal and other xenoantibodies on porcine thymic engraftment and to examine the potential of thymic tissue to tolerize anti-alphaGal antibody-producing cells. Thymectomized [adult thymectomy (ATX)] non-immunized and rabbit red blood cell (RRBC) pre-transplant immunized alphaGal-KO (knockout), wild-type (WT) and mu chain KO B6 mice were treated with 3Gy total body irradiation (TBI), and T and natural killer (NK) cell depleting monoclonal antibodies (mAbs). These conditioned mice were grafted with fetal porcine thymus and liver (FP THY/LIV) tissue under the kidney capsule. Flow cytometric analysis was performed to follow CD4 reconstitution as a measure of FP THY engraftment and function. Only mice with >10% CD4(+) peripheral blood lymphocytes (PBL) were considered successfully engrafted. Enzyme-linked immunosorbent assay (ELISA) was used to assess the kinetics of immunoglobulin M (IgM) and IgG anti-alphaGal antibodies. Anti-pig antibodies were monitored by flow cytometry (FCM). FP THY engrafted successfully in most of the immunoglobulin deficient mice (11 out of 12, 92%) and the outcome was similar in WT B6 controls (8 out of 12, 67%). Non-immunized alphaGal-KO mice grafted with FP THY had a similar success rate (7 out of 11) to that observed in non-immunized alphaGal-WT controls (2 out of 4). In contrast, alphaGal-KO mice immunized pre-transplant with RRBC, then grafted with FP THY/LIV, showed a significant reduction in the success of thymic grafting (2 out of 9, 22%) compared with pre-transplant immunized WT controls (4 out of 7; 57%) and non-immunized alphaGal-KO mice (7 out of 11, 64%). Anti-Gal and anti-pig antibody levels were not markedly augmented by porcine thymus grafts in mice with successful thymus grafts. FP THY engraftment is impaired in the presence of high levels of anti-alphaGal xenoantibodies. However, low levels of anti-alphaGal antibodies and other mouse anti-pig NAbs appear not to play a major role in the rejection of FP THY. Although grafting FP THY expressing the alphaGal epitope did not tolerize B cells producing anti-alphaGal antibodies in a T-cell independent manner, it prevented T-cell dependent sensitization by inducing T-cell tolerance to porcine antigens. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Surg Serv, Transplanta Biol Res Ctr,Bone Marrow Transplantat, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Surg Serv, Transplanta Biol Res Ctr,Bone Marrow Transplantat, Bldg 149-5102,13th St, Boston, MA 02129 USA. RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011 FU NHLBI NIH HHS [P01 HL 18 646]; NIAID NIH HHS [P01 AI139 755] NR 59 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2003 VL 10 IS 1 BP 24 EP 40 DI 10.1034/j.1399-3089.2003.01104.x PG 17 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 636UH UT WOS:000180475300005 PM 12535223 ER PT J AU Gollackner, B Ryan, D Knosalla, C Basker, M Alwayn, IPJ Harper, D Salomon, G Mauiyyedi, S Correa, L Thall, A Cooper, DKC AF Gollackner, B Ryan, D Knosalla, C Basker, M Alwayn, IPJ Harper, D Salomon, G Mauiyyedi, S Correa, L Thall, A Cooper, DKC TI An exploratory investigation of the effect of arsenic trioxide on anti-Gal antibody production in baboons SO XENOTRANSPLANTATION LA English DT Article DE anti-alpha Gal antibodies; arsenic trioxide; baboons; B cells; plasma cells; xenotransplantation ID B-CELL LYMPHOMA; NATURAL ANTIBODIES; DEPLETION; APOPTOSIS; ANTI-CD22 AB Background: Arsenic trioxide (As-2 O-3 ) is an anticancer drug that has been reported to induce apoptosis and inhibit differentiation in human plasmacytoma and normal plasma/B cells without significant myelosuppression. We assessed the ability of As-2 O-3 as single therapy or in combination with an anti-CD20 monoclonal antibody (mAb) and whole body irradiation (WBI) to deplete B and plasma cells, both in vitro and in vivo, and to reduce the level of anti-alphaGal1-3Gal antibody (anti-Gal Ab) in baboons. Methods: In vitro the effect of As-2 O-3 on antibody secretion (anti-Gal IgM, total IgG and IgM) was measured by enzyme-linked immunospot assay (ELISPOT). Its inhibition of proliferation of baboon splenocytes and the NCI-H929 human plasmacytoma cell line was measured by tritiated thymidine uptake. In vivo: all baboons (n=7) had undergone splenectomy. The effects of As-2 O-3 (0.18 to 0.36 mg/kg) on B/plasma cell depletion and anti-Gal Ab production were assessed in three baboons. For comparison, three baboons received either WBI (2 x 150 cGy) or anti-CD20 mAb (20 mg/kg x 4 doses), or both WBI and anti-CD20 mAb. A final baboon received As-2 O-3 + WBI (150 cGy) + anti-CD20 mAb. Anti-Gal Ab levels were measured daily by ELISA. Depletion of B cells from blood and bone marrow (BM) was monitored by flow cytometry and by histology of lymph nodes (LN). Autopsy was performed in three baboons. Results: In vitro: As-2 O-3 (at 5 x 10(-6) mol/l) reduced anti-Gal IgM and total IgM secretors by 76% (P =0.53) and 95% (P < 0.001), respectively, but did not reduce total IgG secretors. As-2 O-3 inhibited in a dose-dependent manner the proliferation of activated splenocytes and of the NCI-H929 plasmacytoma cell line; complete inhibition was achieved at a dose of 1 x 10(-5) mol/l. In vivo: As-2 O-3 was found to be toxic at the doses given and was associated with the deaths of two of the four baboons that received it. Daily intravenous therapy with As-2 O-3 alone reduced B cells (CD20+) in the blood (by 50 to 90%), BM (40%) and LN (20 to 30%), but anti-Gal Ab levels were not significantly decreased. Anti-CD20 mAb therapy alone or WBI alone depleted B cells by 100% in the blood and BM, and 80 to 100% in the LN. The combination of anti-CD20 mAb + WBI led to depletion of B cells in blood, BM and LN for 3 months, but reduction of anti-Gal Ab remained marginal. The combination of As-2 O-3 + anti-CD20 mAb + WBI did not reduce anti-Gal Ab levels further. At autopsy in the latter baboon, B cells remained present in Peyer's patches and tonsils. Conclusions: In vitro: As-2 O-3 reduced B/plasma cell numbers and suppressed IgM secretors, but not IgG secretors. In vivo: As-2 O-3 was not as effective as either anti-CD20 mAb or WBI in depleting B/plasma cells, and was largely ineffective in reducing anti-Gal Ab levels. Its administration was associated with considerable toxicity. Autopsy in one baboon suggested that B cells in Peyer's patches and tonsils may be resistant to therapy and remain a source of continuing production of anti-Gal Ab. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge BioTherapeut Inc, Charlestown, MA USA. BioTransplant Inc, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [1P01 AI45897] NR 16 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2003 VL 10 IS 1 BP 80 EP 87 DI 10.1034/j.1399-3089.2003.01136.x PG 8 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 636UH UT WOS:000180475300011 PM 12535229 ER PT J AU Buhler, L Xu, Y Li, W Zhu, A Cooper, DKC AF Buhler, L Xu, Y Li, W Zhu, A Cooper, DKC TI An investigation of the specificity of induced anti-pig antibodies in baboons SO XENOTRANSPLANTATION LA English DT Article DE natural antibody; pig-to-non-human primate; sensitization; xenotransplantation ID TOLERANCE INDUCTION; NATURAL ANTIBODIES; PORCINE; TRANSPLANTATION; XENOANTIGENS AB Aim : To provide information on the specificity of induced anti-pig antibodies (Abs) in baboons after exposure and sensitization to pig antigens. Materials and methods : Baboons (n=7) received either porcine mobilized peripheral blood progenitor cells (n=3), kidney (n=3) or heart (n=1) transplants. After rejection of these cells or organs, pre- and post-rejection sera were analyzed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry to detect and measure anti-Galactosealpha1,3Galactose (Gal) and anti-non-Gal Abs. To study the anti-non-Gal carbohydrate response, the sera were incubated with pig red blood cells pretreated with alpha-galactosidase (to remove Gal) and three other exoglycosidases to remove other potential oligosaccharide epitopes, and studied by flow cytometry. To study the anti-swine leukocyte antigen (SLA) response, non-Gal Abs from two baboons sensitized with kidneys from inbred miniature swine of dd or aa haplotype, respectively, were adsorbed on cells of aa, cc, or dd haplotypes, and binding to aa, cc or dd cells was measured by flow cytometry. Cytotoxicity of anti-non-Gal Abs was tested in vitro by a complement-mediated cytotoxicity assay, using pig cells as targets. Results : In pre-transplant and pre-rejection sera, anti-Gal Abs were detected, but anti-non-Gal Abs were either absent or at minimal levels. After exposure to pig antigens, baboons developed induced anti-Gal and anti-non-Gal Abs. No anti-non-Gal Abs directed to the tested carbohydrate epitopes could be detected. Anti-non-Gal Abs showed minor evidence of specific SLA haplotype reactivity, suggesting that the major Ab response was to pan-pig determinants. Anti-non-Gal Abs showed a low level of complement-mediated lysis of pig cells in vitro. Conclusions : In this limited study, no Ab response to non-Gal carbohydrates was observed, and anti-SLA specificity was minor, indicating that most induced anti-non-Gal Ab was directed against non-specific pig proteins, including SLA-epitopes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge BioTherapeut Inc, Charlestown, MA USA. New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [5P01 AI39755] NR 15 TC 39 Z9 39 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2003 VL 10 IS 1 BP 88 EP 94 DI 10.1034/j.1399-3089.2003.01122.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 636UH UT WOS:000180475300012 PM 12535230 ER PT J AU Wunder, A Grimm, J Muller-Ladner, U AF Wunder, A Grimm, J Muller-Ladner, U TI Molecular imaging in rheumatoid arthritis SO ZEITSCHRIFT FUR RHEUMATOLOGIE LA German DT Article; Proceedings Paper CT Workshop of the Working Group of Regional Cooperative Rheumatism Centers CY 2003 CL REGENSBURG, GERMANY DE rheumatoid arthritis; molecular markers; molecular imaging; radiological diagnostics; fluorescence imaging ID INFLAMMATION; WRIST AB Advances in molecular biology and technical developments in the field of imaging are increasingly allowing for non-invasive visualization and quantitation of biological processes at the molecular level. Such technologies, defined as molecular imaging, promise early diagnosis and improved classification of the stage and severity of disease, objective assessment of treatment efficacy, and reliable prognosis based on so-called molecular markers. Furthermore, molecular imaging is an important tool for the evaluation of physiological and pathophysiological processes and for drug development. Various different imaging modalities are available, such as conventional radiography (CR), computed tomography (CT), nuclear imaging, magnetic resonance imaging (MRI), ultrasound (US), as well as other methods including fluorescence-based optical imaging. These methods differ with respect to resolution and their potential to gather information at the anatomical, physiological, cellular and molecular level. Therefore, the choice of the imaging modality for molecular imaging depends on the questions that need to be answered. This review discusses the potential of imaging modalities for molecular imaging in rheumatoid arthritis (RA). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Deutsch Krebsforschungszentrum, Forschungsschwerpunkt Innovat Krebsdiagnost & The, D-69120 Heidelberg, Germany. Univ Klinikum Schleswig Holstein, Radiol Diagnost Klin, D-24105 Kiel, Germany. Univ Regensburg, Klin & Poliklin Innere Med 1, D-93042 Regensburg, Germany. RP Wunder, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 146,13th St, Charlestown, MA 02129 USA. EM awunder@hms.harvard.edu; jgrimm@helix.mgh.harvard.edu; ulf.mueller-ladner@klinik.uni-regensburg.de RI Grimm, Jan/B-1937-2008 NR 15 TC 2 Z9 2 U1 1 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-1855 J9 Z RHEUMATOL JI Z. Rheumatol. PY 2003 VL 62 SU 2 BP 33 EP 36 DI 10.1007/s00393-003-1210-7 PG 4 WC Rheumatology SC Rheumatology GA 770LJ UT WOS:000188732000009 ER PT J AU Barbara, PD Van Den Brink, GR Roberts, DJ AF Barbara, PD Van Den Brink, GR Roberts, DJ TI Molecular etiology of gut malformations and diseases SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Review DE gut development; BMP; Sonic hedgehog; Gli family proteins; Hox; tracheo-esophageal fistula; juvenile polyposis syndrome; enteric neural crest; pyloric stenosis ID HYPERTROPHIC PYLORIC-STENOSIS; FAMILIAL JUVENILE POLYPOSIS; SMAD INTERACTING PROTEIN-1; SONIC-HEDGEHOG; HIRSCHSPRUNG-DISEASE; VACTERL-ASSOCIATION; ESOPHAGEAL ATRESIA; LUNG MORPHOGENESIS; GERMLINE MUTATIONS; 25-YEAR EXPERIENCE AB This review describes recent advances using animal models in the analysis of the molecular controls of gastrointestinal development, with specific attention to mutations causing maldevelopment similar to those seen in human gut malformations. By focusing on specific human gut pathologic conditions and maldevelopment, we describe the probable roles of signaling pathways, including the hedgehog pathway, the bone morphogenic protein pathway, and the role of the homeotic genes. (C) 2002 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Roberts, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. NR 113 TC 34 Z9 34 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 30 PY 2002 VL 115 IS 4 BP 221 EP 230 DI 10.1002/ajmg.10978 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 637RV UT WOS:000180527500003 ER PT J AU Tilly, JL Kolesnick, RN AF Tilly, JL Kolesnick, RN TI Sphingolipids, apoptosis, cancer treatments and the ovary: investigating a crime against female fertility SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE ceramide; sphingosine-1-phosphate; apoptosis; cell death; ovary; oocyte; fertility ID PROGRAMMED CELL-DEATH; CYTOCHROME-C; SPHINGOSINE; SPHINGOSINE-1-PHOSPHATE; ACTIVATION; RECEPTORS; BAX; MITOCHONDRIA; SUPPRESSION; MEDIATOR AB Premature ovarian failure and infertility are well-known side-effects observed in young girls and reproductive-age women treated for cancer. Although the need for tumor eradication in these patients is clear, the long-term consequences of chemotherapy and radiation on nontarget tissues, such as the ovaries where large numbers of germ cells (oocytes) are also killed off, are substantial. Unfortunately, the mechanism mediating the undesirable toxicity of cancer therapies in the female gonads has only recently been explored. Nevertheless, some important insights into the role of ceramide and sphingosine-1-phosphate (S1P) as a mediator and suppressor, respectively, of cancer therapy-induced oocyte apoptosis have emerged over the past few years. Such findings are exciting in that a better understanding of the crime-how radiation and chemotherapy kill off this irreplaceable population of innocent cells in the ovaries-may finally allow for the development of novel lipid-based strategies to combat infertility and premature menopause in female cancer patients. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, New York, NY 10021 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, 55 Fruit St,VBK137E-GYN, Boston, MA 02114 USA. FU NCI NIH HHS [R01-CA85704, R01-CA52462]; NIA NIH HHS [R01-AG12279]; NIEHS NIH HHS [R01-ES08430] NR 32 TC 49 Z9 62 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD DEC 30 PY 2002 VL 1585 IS 2-3 BP 135 EP 138 AR PII S1388-1981(02)00333-5 DI 10.1016/S1388-1981(02)00333-5 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 640NL UT WOS:000180694800011 PM 12531546 ER PT J AU Obeid, LA Okamoto, Y Mao, CG AF Obeid, LA Okamoto, Y Mao, CG TI Yeast sphingolipids: metabolism and biology SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE yeast; sphingolipid; cell regulation ID LONG-CHAIN BASES; GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED PROTEINS; SPHINGANINE N-ACYLTRANSFERASE; FATTY-ACID ELONGATION; SACCHAROMYCES-CEREVISIAE; SERINE PALMITOYLTRANSFERASE; HEAT-STRESS; ALKALINE CERAMIDASE; ENDOPLASMIC-RETICULUM; GROWTH-INHIBITION AB Sphingolipids have recently emerged as important bioactive molecules in addition to being critical structural components of cellular membranes. These molecules have been implicated in regulating cell growth, differentiation, angiogenesis, apoptosis, and senescene. To study sphingolipid mediated biology, it is necessary to investigate sphingolipid metabolism and its regulation. The yeast Saccharomyces cerevisiae has allowed such studies to take place as the sphingolipid metabolic and regulatory pathways appear conserved across species. Using yeast genetic approaches most enzymes of sphingolipid metabolism have been identified and cloned which has led to identification of their mammalian homologues. Many of the yeast enzymes are targets of fungal toxins thus underscoring the importance of this pathway in yeast cell regulation. This review focuses on the yeast sphingolipid metabolic pathway and its role in regulation of yeast biology. Implication of the insights gained from yeast to mammalian cell regulation are discussed. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. RP Obeid, LA (reprint author), Med Univ S Carolina, Dept Med, POB 250779,114 Doughty St, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [AG16583]; NIGMS NIH HHS [GM62887] NR 71 TC 89 Z9 91 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD DEC 30 PY 2002 VL 1585 IS 2-3 BP 163 EP 171 AR PII S1388-1981(02)00337-2 DI 10.1016/S1388-1981(02)00337-2 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 640NL UT WOS:000180694800015 PM 12531550 ER PT J AU van Roon-Mom, WMC Reid, SJ Jones, AL MacDonald, ME Faull, RLM Snell, RG AF van Roon-Mom, WMC Reid, SJ Jones, AL MacDonald, ME Faull, RLM Snell, RG TI Insoluble TATA-binding protein accumulation in Huntington's disease cortex SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Huntington's disease; TATA-binding protein; huntingtin; human brain; polyglutamine; middle frontal gyrus ID NEURONAL INTRANUCLEAR INCLUSIONS; NEURODEGENERATIVE DISEASES; GLUTAMINE REPEATS; MUTANT HUNTINGTIN; EXPANDED POLYGLUTAMINE; GENE-PRODUCT; NUCLEAR; EXPANSION; TRANSCRIPTION; LOCALIZATION AB Huntington's disease is a dominantly inherited neurological disorder where specific neurodegeneration is caused by an extended polyglutamine stretch in the huntingtin protein. Proteins with expanded polyglutamine regions have the ability to self-aggregate and previous work in our laboratory, and by others, revealed sparse amyloid-like deposits in the Huntington's disease brain, supporting the hypothesis that the polyglutamine stretches may fold into regular P-sheet structures. This process of folding has similarities to other neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and the prion diseases which all exhibit P-sheet protein accumulation. We were therefore interested in testing the hypothesis that TATA-binding protein may play a role in Huntington's disease as it contains an elongated polymorphic polyglutamine stretch that ranges in size from 26 to 42 amino acids in normal individuals. A proportion of TBP alleles fall within the range of glutamine length that causes neurodegeneration when located in the huntingtin protein. In this study the distribution and cellular localisation of TATA-binding protein was compared to the distribution and cellular localisation of the huntingtin protein in the middle frontal gyrus of Huntington's disease and neurologically normal subjects. Seven different morphological forms of TATA-binding protein-positive structures were detected in Huntington's disease but not in control brain. TATA-binding protein labelling was relatively more abundant than huntingtin labelling and increased with the grade of the disease. At least a proportion of this accumulated TBP exists as insoluble protein. This suggests that TBP may play a role in the disease process. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Auckland, Fac Med & Hlth Sci, Div Mol Med, Auckland 1, New Zealand. Univ Auckland, Fac Med & Hlth Sci, Div Anat & Radiol, Auckland 1, New Zealand. Univ Wales Coll Med, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Snell, RG (reprint author), Univ Auckland, Fac Med & Hlth Sci, Div Mol Med, Auckland 1, New Zealand. RI turton, miranda/F-4682-2011; Reid, Suzanne/H-7082-2012; OI Reid, Suzanne/0000-0002-8068-6529 NR 48 TC 11 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 30 PY 2002 VL 109 IS 1-2 BP 1 EP 10 AR PII S0169-328X(02)00450-3 DI 10.1016/S0169-328X(02)00450-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 641PA UT WOS:000180752600003 ER PT J AU Kimble, MO Kaufman, ML Leonard, LL Nestor, PG Riggs, DS Kaloupek, DG Bachrach, P AF Kimble, MO Kaufman, ML Leonard, LL Nestor, PG Riggs, DS Kaloupek, DG Bachrach, P TI Sentence completion test in combat veterans with and without PTSD: preliminary findings SO PSYCHIATRY RESEARCH LA English DT Article DE posttraumatic stress disorder; semantic processing; information processing; hypervigilance ID POSTTRAUMATIC-STRESS-DISORDER AB This study used a sentence completion task to assess semantic choice in combat veterans. Twenty-eight combat veterans with (n = 14) and without (n = 14) posttraumatic stress disorder (PTSD) filled in the final word for 33 incomplete sentences after receiving a combat prime. The veterans with PTSD completed sentences with significantly more trauma-relevant final words than those without PTSD. Findings are interpreted with respect to current language models and information-processing theories of PTSD. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Boston Univ, Sch Med, Boston VA Healthcare Network, Behav Sci Div,Natl Ctr PTSD, Boston, MA 02130 USA. Univ Las Vegas, Dept Psychol, Reno, NV USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. RP Kimble, MO (reprint author), Univ Wales, Dept Psychol, Bangor Brigantia Bldg, Bangor LL57 2AS, Gwynedd, Wales. OI Kaloupek, Danny/0000-0002-0795-593X FU NIMH NIH HHS [MH19836-01, MH19836-02, 1 R29 MH58215-01A1] NR 11 TC 10 Z9 11 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 30 PY 2002 VL 113 IS 3 BP 303 EP 307 AR PII S0165-1781(02)00229-9 DI 10.1016/S0165-1781(02)00229-9 PG 5 WC Psychiatry SC Psychiatry GA 643VL UT WOS:000180881900009 PM 12559486 ER PT J AU Mischoulon, D Dougherty, DD Bottonari, KA Gresham, RL Sonawalla, SB Fischman, AJ Fava, M AF Mischoulon, D Dougherty, DD Bottonari, KA Gresham, RL Sonawalla, SB Fischman, AJ Fava, M TI An open pilot study of nefazodone in depression with anger attacks: relationship between clinical response and receptor binding SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE neuroimaging; serotonin; receptor; dopamine; antidepressant; positron emission tomography (PET) ID POSITRON-EMISSION-TOMOGRAPHY; MAJOR DEPRESSION; DOUBLE-BLIND; ANTIDEPRESSANT TREATMENT; SEROTONIN(2) RECEPTORS; UNIPOLAR DEPRESSION; SLEEP ARCHITECTURE; OUTPATIENTS; FLUOXETINE; DISORDERS AB Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [F-18]-setoperone for 5HT2 binding potential (BP) and [C-11]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [F-18]-setoperone and with [C-11]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as greater than or equal to 50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. NR 49 TC 25 Z9 25 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 30 PY 2002 VL 116 IS 3 BP 151 EP 161 AR PII S0925-4927(02)00082-3 DI 10.1016/S0925-4927(02)00082-3 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 637WB UT WOS:000180535800002 PM 12477599 ER PT J AU Pauler, DK Finkelstein, DM AF Pauler, DK Finkelstein, DM TI Predicting time to prostate cancer recurrence based on joint models for non-linear longitudinal biomarkers and event time outcomes SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the International-Society-for-Clinical-Biostatistics CY AUG 19-23, 2001 CL STOCKHOLM, SWEDEN SP Int Soc Cliln Biostat DE PSA screening; recurrences; Bayesian modelling; Markov chain Monte Carlo ID RADIATION-THERAPY; ANTIGEN DENSITY; MARKER; ADENOCARCINOMA; RADIOTHERAPY; SURVIVAL; FAILURE; AIDS AB Biological markers that are both sensitive and specific for tumour regrowth or metastasis are increasingly becoming available and routinely monitored during the regular follow-up of patients treated for cancer. Obtained by a simple blood test, these markers provide an inexpensive non-invasive means for the early detection of recurrence (or progression). Currently, the longitudinal behaviour of the marker is viewed as an indicator of early disease progression, and is applied by a physician in making clinical decisions. One marker that has been studied for use in both population screening for early disease and for detection of recurrence in prostate cancer patients is PSA. The elevation of PSA levels is known to precede clinically detectable recurrence by 2 to 5 years, and current clinical practice often relies partially on multiple recent rises in PSA to trigger a change in treatment. However, the longitudinal trajectory for individual markers is often non-linear in many cases there is a decline immediately following radiation therapy or surgery, a plateau during remission, followed by an exponential rise following the recurrence of the cancer. The aim of this article is to determine the multiple aspects of the longitudinal PSA biomarker trajectory that can be most sensitive for predicting time to clinical recurrence. Joint Bayesian models for the longitudinal measures and event times are utilized based on non-linear hierarchical models, implied by unknown change-points, for the longitudinal trajectories, and a Cox proportional hazard model for progression times, with functionals of the longitudinal parameters as covariates in the Cox model. Using Markov chain Monte Carlo sampling schemes, the joint model is fit to longitudinal PSA measures from 676 patients treated at Massachusetts General Hospital between the years 1988 and 1995 with follow-up to 1999. Based on these data, predictive schemes for detecting cancer recurrence in new patients based on their longitudinal trajectory are derived. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Pauler, DK (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MP-702, Seattle, WA 98109 USA. FU NCI NIH HHS [CA 74302] NR 27 TC 32 Z9 32 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 30 PY 2002 VL 21 IS 24 BP 3897 EP 3911 DI 10.1002/sim.1392 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 629FK UT WOS:000180039600011 PM 12483774 ER PT J AU Call, ME Pyrdol, J Wiedmann, M Wucherpfennig, KW AF Call, ME Pyrdol, J Wiedmann, M Wucherpfennig, KW TI The organizing principle in the formation of the T cell receptor-CD3 complex SO CELL LA English DT Article ID ANTIGEN RECEPTOR; SURFACE EXPRESSION; TCR/CD3 COMPLEX; MULTIVALENT STRUCTURE; TRANSMEMBRANE DOMAIN; MEMBRANE-PROTEIN; CD3-GAMMA CHAIN; CD3 COMPLEX; IN-VITRO; ASSOCIATION AB The T cell receptor (TCR) serves a critical function in the immune system and represents one of the most complex receptor structures. A striking feature is the presence of nine highly conserved, potentially charged residues in the transmembrane helices. Previous models have attempted to explain assembly based on pairwise interactions of these residues. Using a novel method for the isolation of intact radiolabeled protein complexes, we demonstrate that one basic and two acidic transmembrane residues are required for the assembly of each of the three signaling dimers with the TCR. This remarkable three-helix arrangement applies to all three assembly steps and represents the organizing principle for the formation of this intricate receptor structure. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Program Immunol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. OI Call, Matthew/0000-0001-5846-6469 FU NIAID NIH HHS [AI45757, P01 AI045757]; NINDS NIH HHS [NS39096, R01 NS039096] NR 34 TC 236 Z9 244 U1 2 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 27 PY 2002 VL 111 IS 7 BP 967 EP 979 DI 10.1016/S0092-8674(02)01194-7 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 630AU UT WOS:000180086000007 PM 12507424 ER PT J AU Yu, CL Chen, Y Cline, GW Zhang, DY Zong, HH Wang, YL Bergeron, R Kim, JK Cushman, SW Cooney, GJ Atcheson, B White, MF Kraegen, EW Shulman, GI AF Yu, CL Chen, Y Cline, GW Zhang, DY Zong, HH Wang, YL Bergeron, R Kim, JK Cushman, SW Cooney, GJ Atcheson, B White, MF Kraegen, EW Shulman, GI TI Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SOLID-PHASE EXTRACTION; SKELETAL-MUSCLE; RESISTANCE; HUMANS; TRIGLYCERIDE; TISSUE; SPECTROSCOPY; ASSOCIATION; THETA; RAT AB Recent studies have demonstrated that fatty acids induce insulin resistance in skeletal muscle by blocking insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase). To examine the mechanism by which fatty acids mediate this effect, rats were infused with either a lipid emulsion (consisting mostly of 18:2 fatty acids) or glycerol. Intracellular C18:2 CoA increased in a time-dependent fashion, reaching an similar to6-fold elevation by 5 h, whereas there was no change in the concentration of any other fatty acyl-CoAs. Diacylglycerol (DAG) also increased transiently after 3-4 h of lipid infusion. In contrast there was no increase in intracellular ceramide or triglyceride concentrations during the lipid infusion. Increases in intracellular C18:2 CoA and DAG concentration were associated with protein kinase C (PKC)-theta activation and a reduction in both insulin-stimulated IRS-1 tyrosine phosphorylation and IRS-1 associated PI3-kinase activity, which were associated with an increase in IRS-1 Ser(307) phosphorylation. These data support the hypothesis that an increase in plasma fatty acid concentration results in an increase in intracellular fatty acyl-CoA and DAG concentrations, which results in activation of PKC-theta leading to increased IRS-1 Ser(307) phosphorylation. This in turn leads to decreased IRS-1 tyrosine phosphorylation and decreased activation of IRS-1-associated PI3-kinase activity resulting in decreased insulin-stimulated glucose transport activity. C1 Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. NIDDK, NIH, Bethesda, MD 20814 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Garvan Inst Med Res, Sydney, NSW, Australia. RP Shulman, GI (reprint author), Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst, 295 Congress Ave,BCMM 254,Box 9812, New Haven, CT 06536 USA. FU NIDDK NIH HHS [R01 DK-40936, P30 DK-45735, R01 DK040936] NR 21 TC 861 Z9 894 U1 2 U2 48 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50230 EP 50236 DI 10.1074/jbc.M200958200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700005 PM 12006582 ER PT J AU Salas, A Shimaoka, M Chen, SQ Carman, CV Springer, T AF Salas, A Shimaoka, M Chen, SQ Carman, CV Springer, T TI Transition from rolling to firm adhesion is regulated by the conformation of the I domain of the integrin lymphocyte function-associated antigen-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHYSIOLOGICAL FLOW; HYDRODYNAMIC FLOW; STRUCTURAL BASIS; P-SELECTIN; BINDING; ICAM-1; LFA-1; NEUTROPHILS; MAC-1; SITE AB The integrin lymphocyte function-associated antigen-1 (alpha(L)beta(2)) which is known for its ability to mediate firm adhesion and migration, can also contribute to tethering and rolling in shear How. The alpha(L) I domain can be mutationally locked with disulfide bonds into two distinct conformations, open and closed, which have high and low affinity for the ligand intercellular adhesion molecule 1 (ICAM-1), respectively. The wild type I domain exists primarily in the lower energy closed conformation. We have measured for the first time the effect of conformational change on adhesive behavior in shear flow. We show that wild type and locked open I domains, expressed in alpha(L)beta(2) heterodimers or as isolated domains on the cell surface, mediate rolling adhesion and firm adhesion, respectively. alpha(L)beta(2) is thus poised for the conversion of rolling to firm adhesion upon integrin activation in vivo. Isolated I domains are surprisingly more effective than alpha(L)beta(2) in interactions in shear flow, which may in part be a consequence of the presence Of alpha(L)beta(2) in a bent conformation. Furthermore, the force exerted on the C-terminal alpha-helix appears to stabilize the open conformation of the wild type isolated I domain and contribute to its robustness in supporting rolling. An allosteric small molecule antagonist of alpha(L)beta(2) inhibits both rolling adhesion and firm adhesion, which has important implications for its mode of action in vivo. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Springer, T (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Carman, Christopher/L-8108-2016; OI Carman, Christopher/0000-0001-7358-2548; Salas, Azucena/0000-0003-4572-2907 FU NCI NIH HHS [CA31798] NR 38 TC 83 Z9 84 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50255 EP 50262 DI 10.1074/jbc.M209822200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700008 PM 12368274 ER PT J AU Fried, MG Stickle, DF Smirnakis, KV Adams, C MacDonald, D Lu, PZ AF Fried, MG Stickle, DF Smirnakis, KV Adams, C MacDonald, D Lu, PZ TI Role of hydration in the binding of lac repressor to DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIC-AMP RECEPTOR; NUCLEIC-ACID INTERACTIONS; ESCHERICHIA-COLI; OSMOTIC-STRESS; THERMODYNAMIC ORIGINS; OPERATOR INTERACTION; MACROMOLECULAR HYDRATION; GEL-ELECTROPHORESIS; LACTOSE REPRESSOR; CRYSTAL-STRUCTURE AB The osmotic stress technique was used to measure changes in macromolecular hydration that accompany binding of wild-type Escherichia coli lactose (lac) repressor to its regulatory site (operator O1) in the lac promoter and its transfer from site O1 to nonspecific DNA. Binding at O1 is accompanied by the net release of 260 +/- 32 water molecules. If all are released from macromolecular surfaces, this result is consistent with a net reduction of solvent-accessible surface area of 2370 550 Angstrom(2). This area is only slightly smaller than the macromolecular interface calculated for a crystalline repressor dimer-O1 complex but is significantly smaller than that for the corresponding complex with the symmetrical optimized O-sym operator. The transfer of repressor from site O1 to nonspecific DNA is accompanied by the net uptake of 93 +/- 10 water molecules. Together these results imply that formation of a nonspecific complex is accompanied by the net release of 165 +/- 43 water molecules. The enhanced stabilities of repressor-DNA complexes with increasing osmolality may contribute to the ability of Escherichia coli cells to tolerate dehydration and/or high external salt concentrations. C1 Penn State Univ, Dept Biochem & Mol Biol, Coll Med, Hershey, PA 17033 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. RP Fried, MG (reprint author), Penn State Univ, Dept Biochem & Mol Biol, Coll Med, POB 850, Hershey, PA 17033 USA. RI Stickle, Douglas/A-9682-2009 NR 73 TC 38 Z9 39 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50676 EP 50682 DI 10.1074/jbc.M208540200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700064 PM 12379649 ER PT J AU Dohadwala, M Batra, RK Luo, J Lin, Y Krysan, K Pold, M Sharma, S Dubinett, SM AF Dohadwala, M Batra, RK Luo, J Lin, Y Krysan, K Pold, M Sharma, S Dubinett, SM TI Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HUMAN PROSTATE; INCREASED EXPRESSION; PANCREATIC-CANCER; CARCINOMA CELLS; TUMOR INVASION; UP-REGULATION; INHIBITION; APOPTOSIS; GROWTH AB Tumor cyclooxygenase-2 (COX-2) expression is known to be associated with enhanced tumor invasiveness. In the present study, we evaluated the importance of the COX-2 product prostaglandin E2 (PGE2) and its signaling through the EP4 receptor in mediating non-small cell lung cancer (NSCLC) invasiveness. Genetic inhibition of tumor COX-2 led to diminished matrix metalloproteinase (MMP)-2, CD44, and EP4 receptor expression and invasion. Treatment of NSCLC cells with exogenous 16,16-dimethylprostaglandin E2 significantly increased EP4 receptor, CD44, and MMP-2 expression and matrigel invasion. In contrast, anti-PGE2 decreased EP4 receptor, CD44, and MMP-2 expression in NSCLC cells. EP4 receptor signaling was found to be central to this process, because antisense oligonucleotide-mediated inhibition of tumor cell EP4 receptors significantly decreased CD44 expression. In addition, agents that increased intracellular cAMP, as is typical of EP4 receptor signaling, markedly increased CD44 expression. Moreover, MMP-2-AS treatment decreased PGE2-mediated CD44 expression, and CD44-AS treatment decreased MMP-2 expression. Thus, PGE2-mediated effects through EP4 required the parallel induction of both CD44 and MMP-2 expression because genetic inhibition of either MMP-2 or CD44 expression effectively blocked PGE2-mediated invasion in NSCLC. These findings indicate that PGE2 regulates COX-2-dependent, CD44- and MMP-2-mediated invasion in NSCLC in an autocrine/paracrine manner via EP receptor signaling. Thus, blocking PGE2 production or activity by genetic or pharmacological interventions may prove to be beneficial in chemoprevention or treatment of NSCLC. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Hlth Care Ctr, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90095 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. OI Batra, Raj K./0000-0002-1126-543X FU NCI NIH HHS [P50 CA090388, P50 CA90388, R01 CA078654, R01CA71818] NR 60 TC 195 Z9 211 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50828 EP 50833 DI 10.1074/jbc.M210707200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700083 PM 12393872 ER PT J AU Sikaneta, T Williams, WW Chung, RT Cosimi, AB Pascual, M AF Sikaneta, T Williams, WW Chung, RT Cosimi, AB Pascual, M TI Remission of hepatitis C virus-associated cryoglobulinemic glomerulonephritis with interferon alfa-2b and ribavirin combination therapy after liver transplantation SO TRANSPLANTATION LA English DT Article C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Box MZ70,55 Fruit St, Boston, MA 02114 USA. NR 5 TC 7 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 2002 VL 74 IS 12 BP 1767 EP 1768 DI 10.1097/01.TP.0000038318.03583.63 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 629HJ UT WOS:000180044000021 PM 12499895 ER PT J AU Benoist, C Mathis, D AF Benoist, C Mathis, D TI Mast cells in autoimmune disease SO NATURE LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; ALTERED PEPTIDE LIGAND; MULTIPLE-SCLEROSIS; T-CELL; PROINFLAMMATORY CYTOKINE; NEUTROPHIL RECRUITMENT; RHEUMATOID-ARTHRITIS; INNATE IMMUNITY; MURINE MODEL AB Mast cells are known to be the primary responders in allergic reactions, orchestrating strong responses to minute amounts of allergens. Several recent observations indicate that they may also have a key role in coordinating the early phases of autoimmune diseases, particularly those involving auto-antibodies. C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Benoist, C (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. NR 55 TC 213 Z9 221 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 26 PY 2002 VL 420 IS 6917 BP 875 EP 878 DI 10.1038/nature01324 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 626WR UT WOS:000179897300069 PM 12490961 ER PT J AU Gong, MN Wittram, C Mark, EJ AF Gong, MN Wittram, C Mark, EJ TI A 56-year-old man with rapidly worsening dyspnea - Usual interstitial pneumonitis (fibrosing alveolitis) entering the accelerated phase, consistent with the clinical diagnosis of acute exacerbation of idiopathic pulmonary fibrosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID OBLITERANS ORGANIZING PNEUMONIA; RESPIRATORY-DISTRESS SYNDROME; SYSTEMIC LUPUS-ERYTHEMATOSUS; ACUTE EOSINOPHILIC PNEUMONIA; THIN-SECTION CT; BRONCHIOLITIS OBLITERANS; LUNG-DISEASE; PATHOLOGICAL FINDINGS; FEATURES; SURVIVAL C1 Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Gong, MN (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. FU NHLBI NIH HHS [K23 HL067197] NR 44 TC 6 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 26 PY 2002 VL 347 IS 26 BP 2149 EP 2157 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 629FZ UT WOS:000180040900009 PM 12501228 ER PT J AU Chee, MWL Caplan, D AF Chee, MWL Caplan, D TI Face encoding and psychometric testing in healthy dextrals with right hemisphere language SO NEUROLOGY LA English DT Article ID FUNCTIONAL MRI; CEREBRAL LATERALIZATION; FRONTAL-CORTEX; TEMPORAL-LOBE; RIGHT-HANDERS; WADA TEST; DOMINANCE; FMRI; BRAIN; ORGANIZATION AB Objective: To document how right hemisphere language dominance in neurologically normal right-handed individuals affects lateralization of face encoding and level of performance in neuropsychological tests. Methods: Three healthy right-handed adults with predominantly right hemisphere language activation during single-word or sentence-level processing were identified from 210 consecutive right-handed subjects studied using blood oxygenation level-dependent contrast fMRI. These three study subjects (S1 to S3) underwent a second scanning session where they performed word and face encoding. Their functional scans were contrasted with those obtained from six healthy control subjects (C1 to C6) with left hemisphere language dominance. Psychometric tests were performed on the study subjects. Results: Right hemisphere-dominant language activation was reproduced in the second scanning session in the three study subjects. The extent to which the lateralization of face encoding was reversed varied. Right hemisphere language was associated with lower (but within normal) verbal IQ compared with performance IQ in two of three volunteers. Verbal and nonverbal memory scores were normal and did not differ appreciably. Conclusion: Right hemisphere-dominant language in healthy dextrals exists but is rare. The extent to which face encoding is reversed in these individuals is variable. Cognitive function does not appear to be significantly compromised even though some psychometric test scores are asymmetric in favor of nonverbal performance when the reversal of lateralization of face and word memory is not complete. C1 Singapore Gen Hosp, Cognit Neurosci Lab, Singapore, Singapore. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Chee, MWL (reprint author), SingHlth Res Facil, Cognit Neurosci Lab, 7th Hosp Ave,1-11, Singapore 169611, Singapore. OI Chee, Michael/0000-0002-6087-0548 FU NIDCD NIH HHS [DC02146] NR 49 TC 5 Z9 8 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 24 PY 2002 VL 59 IS 12 BP 1928 EP 1934 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 627JY UT WOS:000179931100018 PM 12499485 ER PT J AU Hinkin, CH Castellon, SA Durvasula, RS Hardy, DJ Lam, MN Mason, KI Thrasher, D Goetz, MB Stefaniak, M AF Hinkin, CH Castellon, SA Durvasula, RS Hardy, DJ Lam, MN Mason, KI Thrasher, D Goetz, MB Stefaniak, M TI Medication adherence among HIV+ adults - Effects of cognitive dysfunction and regimen complexity SO NEUROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; SELF-REPORTED ADHERENCE; NEUROPSYCHOLOGICAL PERFORMANCE; DRUG-RESISTANCE; INFECTION; PATIENT; AIDS; INDIVIDUALS; TRIAL AB Background: Although the use of highly active antiretroviral therapy in the treatment of HIV infection has led to considerable improvement in morbidity and mortality, unless patients are adherent to their drug regimen (i.e., at least 90 to 95% of doses taken), viral replication may ensue and drug-resistant strains of the virus may emerge. Methods: The authors studied the extent to which neuropsychological compromise and medication regimen complexity are predictive of poor adherence in a convenience sample of 137 HIV-infected adults. Medication adherence was tracked through the use of electronic monitoring technology (MEMS caps). Results: Two-way analysis of variance revealed that neurocognitive compromise as well as complex medication regimens were associated with significantly lower adherence rates. Cognitively compromised participants on more complex regimens had the greatest difficulty with adherence. Deficits in executive function, memory, and attention were associated with poor adherence. Logistic regression analysis demonstrated that neuropsychological compromise was associated with a 2.3 times greater risk of adherence failure. Older age (>50 years) was also found to be associated with significantly better adherence. Conclusions: HIV-infected adults with significant neurocognitive compromise are at risk for poor medication adherence, particularly if they have been prescribed a complex dosing regimen. As such, simpler dosing schedules for more cognitively impaired patients might improve adherence. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. Calif State Univ Los Angeles, Dept Psychol, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90032 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Hinkin, CH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA. OI Goetz, Matthew/0000-0003-4542-992X FU NIMH NIH HHS [R01 MH58552, R01 MH058552, R01 MH058552-05, T32 MH019535] NR 52 TC 231 Z9 237 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 24 PY 2002 VL 59 IS 12 BP 1944 EP 1950 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 627JY UT WOS:000179931100021 PM 12499488 ER PT J AU Faber, PW Voisine, C King, DC Bates, EA Hart, AC AF Faber, PW Voisine, C King, DC Bates, EA Hart, AC TI Glutamine/proline-rich PQE-1 proteins protect Caenorhabditis elegans neurons from huntingtin polyglutamine neurotoxicity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXPANDED POLYGLUTAMINE; CELL-DEATH; C-ELEGANS; NEURODEGENERATIVE DISEASES; MOLECULAR ASPECTS; SENSORY NEURON; GENE; DROSOPHILA; AGGREGATION; REPEATS AB Huntington's disease is a progressive neurodegenerative disease caused by a polyglutamine (polyQ) repeat expansion in the huntingtin protein [Huntington's Disease Collaborative Research Group (1993) Cell 72, 971-983]. To understand the mechanism by which polyQ repeats cause neurodegeneration and cell death, we modeled polyQ neurotoxicity in Caenorhabditis elegans. In our model, expression of N-terminal fragments of human huntingtin causes polyQ-dependent degeneration of neurons. We conducted a genetic screen to identify proteins that protect neurons from the toxic effects of expanded polyQ tracts. Loss of polyQ enhancer-1 (pqe-1) gene function strongly and specifically exacerbates neurodegeneration and cell death, whereas overexpression of a pqe-1 cDNA protects C. elegans neurons from the toxic effects of expanded huntingtin fragments. A glutamine/proline-rich domain, along with a charged domain, is critical for PQE-1 protein function. Analysis of pqe-1 suggests that proteins exist that specifically protect neurons from the toxic effects of expanded polyQ disease proteins. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Massachusetts Gen Hosp, Ctr Canc, 149-7202 13th St, Charlestown, MA 02129 USA. EM hart@helix.mgh.havard.edu FU NINDS NIH HHS [R01 NS040048-05, R01 NS040048] NR 54 TC 70 Z9 78 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 DEC 24 PY 2002 VL 99 IS 26 BP 17131 EP 17136 DI 10.1073/pnas.262544899 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 630HN UT WOS:000180101600111 PM 12486229 ER PT J AU Wolkow, CA Munoz, MJ Riddle, DL Ruvkun, G AF Wolkow, CA Munoz, MJ Riddle, DL Ruvkun, G TI Insulin receptor substrate and p55 orthologous adaptor proteins function in the Caenorhabditis elegans daf-2/insulin-like signaling pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DAUER LARVA DEVELOPMENT; AGE-1 PI3 KINASE; LIFE-SPAN; PHOSPHOINOSITIDE 3-KINASE; TRANSCRIPTION FACTOR; INTERACTING GENES; FAMILY MEMBER; MICE LACKING; LONGEVITY; DAF-2 AB An insulin-like signaling pathway regulates development and lifespan in Caenorhabditis elegdns. Genetic screens that identified many components of the C. elegans insulin pathway did not identify homologs of insulin receptor substrates or the phosphoinositide 3-kinase (PI3K) adaptor/regulatory subunit, which are both required for signaling by mammalian insulin/insulin-like growth factor I pathways. The C. elegans genome contains one homolog of each protein. The C. elegans versions of insulin receptor substrate (IST-1) and PI3K p50/p55 (AAP-1) share moderate sequence similarity with their vertebrate and Drosophila counterparts. Genetic experiments show that ist-1 and aap-1 potentiate C. elegans insulin-like signaling, although they are not required for signaling in the pathway under most conditions. Worms lacking AAP-1 activity because of the mutation aap-1(m889) constitutively arrest development at the dauer larval stage when raised at high temperatures. aap-1 mutants also live longer than wild-type animals, a phenotype observed in other C. elegans mutants with defects in DAF-2 signaling. Interestingly, IST-1 appears to be required for signaling through a pathway that may act in parallel to AGE-1/PI3K. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Wolkow, CA (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RI Munoz, Manuel/F-7841-2016 FU Intramural NIH HHS [NIH0011061953, Z01 AG000320-06]; NIA NIH HHS [AG 12689, AG 14161, R01 AG014161]; NIGMS NIH HHS [GM 60151] NR 43 TC 62 Z9 68 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49591 EP 49597 DI 10.1074/jbc.M207866200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900065 PM 12393910 ER PT J AU Caterina, JJ Skobe, Z Shi, J Ding, YL Simmer, JP Birkedal-Hansen, H Bartlett, JD AF Caterina, JJ Skobe, Z Shi, J Ding, YL Simmer, JP Birkedal-Hansen, H Bartlett, JD TI Enamelysin (matrix metalloproteinase 20)-deficient mice display an amelogenesis imperfecta phenotype SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX PROTEINS; MOUSE ENAMELYSIN; MESSENGER-RNAS; BOVINE ENAMEL; CLONING; TOOTH; GENE; EXPRESSION; LOCALIZATION; CELLS AB Enamelysin is a tooth-specific matrix metalloproteinase that is expressed during the early through middle stages of enamel development. The enamel matrix proteins amelogenin, ameloblastin, and enamelin are also expressed during this same approximate developmental time period, suggesting that enamelysin may play a role in their hydrolysis. In support of this interpretation, recombinant enamelysin was previously demonstrated to cleave recombinant amelogenin at virtually all of the precise sites known to occur in vivo. Thus, enamelysin is likely an important amelogenin-processing enzyme. To characterize the in vivo biological role of enamelysin during tooth development, we generated an enamelysin-deficient mouse by gene targeting. Although mice heterozygous for the mutation have no apparent phenotype, the enamelysin null mouse has a severe and profound tooth phenotype. Specifically, the null mouse does not process amelogenin properly, possesses an altered enamel matrix and rod pattern, has hypoplastic enamel that delaminates from the dentin, and has a deteriorating enamel organ morphology as development progresses. Our findings demonstrate that enamelysin activity is essential for proper enamel development. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. NIDCR, Matrix Metalloproteinase Unit, NIH, Bethesda, MD 20892 USA. Forsyth Inst, Biostruct Core Facil, Boston, MA 02115 USA. Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48108 USA. Harvard Univ, Sch Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. FU NIDCR NIH HHS [R01 DE014084, DE 14084] NR 54 TC 154 Z9 156 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49598 EP 49604 DI 10.1074/jbc.M209100200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900066 PM 12393861 ER PT J AU Kim, DY Ingano, LAM Kovacs, DM AF Kim, DY Ingano, LAM Kovacs, DM TI Nectin-1 alpha, an immunoglobulin-like receptor involved in the formation of synapses, is a substrate for presenilin/gamma-secretase-like cleavage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; ADHERENS JUNCTIONS; COMPLEX-FORMATION; NOTCH; CADHERIN; ASSOCIATION; RELEASE; DOMAIN; FAMILY; ENTRY AB Nectin-1 is a member of the immunoglobulin superfamily and a Ca2+-independent adherens junction protein involved in synapse formation. Here we show that nectin-la undergoes intramembrane proteolytic processing analogous to that of the Alzheimer's disease amyloid precursor protein, mediated by a presenilin (PS)-dependent gamma-secretase-like activity. 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment of Chinese hamster ovary cells activated a first proteolytic event, resulting in ectodomain shedding of nectin-la. Subsequent cleavage of the remaining 26-kDa membrane-anchored C-terminal fragment (CTF) was inhibited independently by three specific gamma-secretase inhibitors and by expression of the dominant negative form of PS1. The PS/gamma-secretase-like cleavage product was detected in vivo following proteasome inhibitor treatment of cells. An in vitro gamma-secretase assay confirmed the generation of a 24-kDa nectin-la intracellular domain, peripherally associated with the membrane fraction. We also found nectin-la to interact with the N-terminal fragment of PS1. Finally, gamma-secretase inhibition resulted in beta-catenin release from cell junctions, concomitantly with the accumulation of the 26-kDa nectin-la CTF, suggesting that high levels of nectin-la CTF interfere with TPA-induced remodeling of cell-cell junctions. Our results are consistent with a previously reported role for PS/gamma-secretase in adherens junction function involving cleavage of cadherins. Similar to nectin-1, other members of the immunoglobulin superfamily involved in synapse formation may also serve as substrates for PS/gamma-secretase-like intramembrane proteolytic activity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Aging Genet & Neurodegenerat, Neurobiol Dis Lab,Genet & Aging Res Unit, Boston, MA 02129 USA. RP Kovacs, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Aging Genet & Neurodegenerat, Neurobiol Dis Lab,Genet & Aging Res Unit, 114 16th St, Boston, MA 02129 USA. NR 31 TC 141 Z9 146 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49976 EP 49981 DI 10.1074/jbc.M210179200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900114 PM 12376527 ER PT J AU Kunjathoor, VV Febbraio, M Podrez, EA Moore, KJ Andersson, L Koehn, S Rhee, JS Silverstein, R Hoff, HF Freeman, MW AF Kunjathoor, VV Febbraio, M Podrez, EA Moore, KJ Andersson, L Koehn, S Rhee, JS Silverstein, R Hoff, HF Freeman, MW TI Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ATHEROSCLEROTIC LESIONS; OXIDIZED LDL; IN-VITRO; SR-PSOX; EXPRESSION; CELLS; CHOLESTEROL; PHOSPHATIDYLSERINE; OXIDATION; MEMBRANE AB Modification of low density lipoprotein (LDL) can result in the avid uptake of these lipoproteins via a family of macrophage transmembrane proteins referred to as scavenger receptors (SRs). The genetic inactivation of either of two SR family members, SR-A or CD36, has been shown previously to reduce oxidized LDL uptake in vitro and atherosclerotic lesions in mice. Several other SRs are reported to bind modified LDL, but their contribution to macrophage lipid accumulation is uncertain. We generated mice lacking both SR-A and CD36 to determine their combined impact on macrophage lipid uptake and to assess the contribution of other SRs to this process. We show that SR-A and CD36 account for 75-90% of degradation of LDL modified by acetylation or oxidation. Cholesteryl ester derived from modified lipoproteins fails to accumulate in macrophages taken from the double null mice, as assessed by histochemistry and gas chromatography-mass spectrometry. These results demonstrate that SR-A and CD36 are responsible for the preponderance of modified LDL uptake in macrophages and that other scavenger receptors do not compensate for their absence. C1 Massachusetts Gen Hosp, Dept Med, Lipid Metab Unit, Boston, MA 02114 USA. Cornell Univ, Weill Med Coll, Dept Med, Div Hematol & Med Oncol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Med, Ctr Vasc Biol, New York, NY 10021 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Dept Med, Lipid Metab Unit, Boston, MA 02114 USA. OI Moore, kathryn/0000-0003-2505-2547 FU NHLBI NIH HHS [F32 HL 10366, HL 45098, HL 53315, HL 66678] NR 30 TC 466 Z9 498 U1 4 U2 30 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49982 EP 49988 DI 10.1074/jbc.M209649200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900115 PM 12376530 ER PT J AU Cohen, GB Islam, SA Noble, MS Lau, C Brander, C Altfeld, MA Rosenberg, ES Schmitz, JE Cameron, TO Kalams, SA AF Cohen, GB Islam, SA Noble, MS Lau, C Brander, C Altfeld, MA Rosenberg, ES Schmitz, JE Cameron, TO Kalams, SA TI Clonotype tracking of TCR repertoires during chronic virus infections SO VIROLOGY LA English DT Article DE T cell receptors; HIV; EBV; CTL ID T-CELL RECEPTOR; LYMPHOCYTE RESPONSES; EFFECTOR FUNCTION; FINE SPECIFICITY; HIV-1 INFECTION; FLOW-CYTOMETRY; IN-VIVO; MEMORY; ANTIGEN; EBV AB Human viral infections such as HIV and EBV typically evoke a strong and diverse CD8(+) T cell response. Relatively little is known about the extent to which TCR repertoire evolution occurs during viral infection or how repertoire evolution affects the efficacy of the CD8(+) T cell response. In this study we describe a general approach for tracking TCR repertoire evolution during viral infection. IFNgamma surface capture and MHC class I tetramer staining were independently used to isolate EBV-specific CD8(+) T cells from peripheral blood. Anchored RT-PCR and clonotype TCR repertoire analysis were performed immediately after isolating the cells. We find that the TCR repertoires of the IFNgamma secreting and MHC class I tetramer staining populations were similar. In one subject a detailed analysis of the TCR repertoire during the first year of EBV infection was performed and over 600 TCR sequences targeting an EBV-immunodominant epitope were analyzed. Although some repertoire evolution occurred during the year, in general, the degree of repertoire drift was small. TCR repertoire analysis for an HIV-immunodominant epitope revealed a highly conserved amino acid motif in the Dbeta region of TCR that recognizes the epitope and suggested that T cell precursor frequency influences which epitopes are targeted early in HIV infection. This methodology, which allows one to sort antigen-specific T cells based on different functional assays and to obtain a snapshot of their TCR repertoire with relative ease, should lead to a richer understanding of the rules underlying antigen recognition and T cell evolution during viral infection. (C) 2002 Elsevier Science (USA). C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. RP Cohen, GB (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Immunol, 1 Pine Hill Dr, Southborough, MA 01772 USA. OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [R01 AI028568, R01 AI039966, AI28568, AI39966] NR 41 TC 26 Z9 26 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2002 VL 304 IS 2 BP 474 EP 484 DI 10.1006/viro.2002.1743 PG 11 WC Virology SC Virology GA 629QM UT WOS:000180060400031 PM 12504586 ER PT J AU Ferrantelli, F Rasmussen, RA Hofmann-Lehmann, R Xu, WD McClure, HM Ruprecht, RM AF Ferrantelli, F Rasmussen, RA Hofmann-Lehmann, R Xu, WD McClure, HM Ruprecht, RM TI Do not underestimate the power of antibodies - lessons from adoptive transfer of antibodies against HIV SO VACCINE LA English DT Article; Proceedings Paper CT Meeting on Therapeutic Vaccines Against HIV and Cancers CY JUN 23-26, 2002 CL ANNECY, FRANCE DE neutralizing antibodies; passive immunization; AIDS vaccine ID IMMUNODEFICIENCY-VIRUS TYPE-1; BROADLY NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL-ANTIBODIES; CELLULAR IMMUNE-RESPONSES; RHESUS-MONKEYS; PRIMATE MODEL; MACAQUES; INFECTION; VIREMIA; VACCINATION AB Successes for neutralizing antibodies (nAbs) against the human immunodeficiency virus (HIV) include potent cross-clade neutralization of primary virus isolates by human neutralizing monoclonal antibodies (nmAbs) targeting conserved envelope epitopes. Furthermore, passively administered combinations of human nmAbs prevented infection in primates, indicating that epitopes recognized by such nmAbs are key determinants for protection. Lastly, in the absence of CD8(+) T cells, nAbs may act as a second line of defense during chronic infection. Taken together, these results argue for generating nAb response-based prophylactic and/or therapeutic AIDS vaccines. We suggest that the epitopes identified by passive immunization represent excellent targets for the rational design of nAb response-based AIDS vaccines. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St JFB809, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009; Ferrantelli, Flavia/J-7794-2016 OI Ferrantelli, Flavia/0000-0002-0768-1078 FU NCRR NIH HHS [RR00165]; NIAID NIH HHS [R01 AI34266, P01 AI48240] NR 36 TC 23 Z9 24 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 19 PY 2002 VL 20 SU 4 BP A61 EP A65 AR PII S0264-410X(02)00389-4 DI 10.1016/S0264-410X(02)00389-4 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 631GR UT WOS:000180160200010 PM 12477430 ER PT J AU Pasternak, RC AF Pasternak, RC TI The AALHAT Lipid Lowering Trial - Less is less SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID AVERAGE CHOLESTEROL LEVELS; CORONARY-DISEASE; PRAVASTATIN; PREVENTION; EVENTS; HYPERCHOLESTEROLEMIA; RISK; MEN C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pasternak, RC (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. NR 23 TC 28 Z9 28 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 18 PY 2002 VL 288 IS 23 BP 3042 EP 3044 DI 10.1001/jama.288.23.3042 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 626CG UT WOS:000179854200041 PM 12479771 ER PT J AU Chung, IM Gold, HK Schwartz, SM Ikari, Y Reidy, MA Wight, TN AF Chung, IM Gold, HK Schwartz, SM Ikari, Y Reidy, MA Wight, TN TI Enhanced extracellular matrix accumulation in restenosis of coronary arteries after stent deployment SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; TRANSFORMING GROWTH FACTOR-BETA-1; BALLOON ANGIOPLASTY; INTRAVASCULAR ULTRASOUND; DUCTUS-ARTERIOSUS; CAROTID ARTERIES; HYALURONAN; PROLIFERATION; LESIONS; MODEL AB OBJECTIVES The goal of this study was to evaluate the cellular and extracellular composition of human coronary arterial in-stent restenosis after various periods of time following stent deployment. BACKGROUND Neointimal in-growth rather than stent recoil is thought to be important for coronary arterial in-stent restenosis. There is only limited data on the cellular and extracellular composition changes with time after stent deployment. METHODS We analyzed 29 coronary arterial in-stent restenotic tissue samples (14 left anterior descending coronary artery, 10 right coronary artery, and 5 left circumflex artery) retrieved by using directional coronary atherectomy from 25 patients at 0.5 to 23 (mean, 5.7) months after deployment of Palmaz-Schatz stents employing histochemical and immunocytochemical techniques. RESULTS Cell proliferation was low (0% to 4%). Myxoid tissue containing extracellular matrix (ECM) enriched with proteoglycans was found in 69% of cases and decreased over time after stenting. Cell-depleted areas were found in 57% of cases and increased with time after stenting. Versican, biglycan, perlecan, and hyaluronan were present with varying individual distributions in all samples. Positive transforming growth factor-beta1 staining was found in 80% of cases. Immunostaining with alpha-smooth muscle actin identified the majority of cells as smooth muscle cells with occasional macrophages present (:! 12 cells per section). CONCLUSIONS These data suggest that enhanced ECM accumulation rather than cell proliferation contribute to later stages of in-stent restenosis. Balloon angioplasty of in-stent restenosis may, therefore, fail due to ECM changes during: 1) additional stent expansion, 2) tissue extrusion out of the stent, or 3) tissue compression. (C) 2002 by the American College of Cardiology Foundation. C1 Hope Heart Inst, Seattle, WA 98104 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Mitsui Mem Hosp, Div Cardiol, Tokyo 101, Japan. RP Wight, TN (reprint author), Hope Heart Inst, 1124 Columbia St,Suite 783, Seattle, WA 98104 USA. FU NHLBI NIH HHS [HL-41103, HL-18645] NR 46 TC 97 Z9 107 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 18 PY 2002 VL 40 IS 12 BP 2072 EP 2081 AR PII S0735-1097(02)02598-6 DI 10.1016/S0735-1097(02)02598-6 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 625UU UT WOS:000179834600002 PM 12505216 ER PT J AU Joffe, S Weeks, JC AF Joffe, S Weeks, JC TI Views of American oncologists about the purposes of clinical trials SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PHYSICIAN-ASSISTED SUICIDE; HIGH-DOSE CHEMOTHERAPY; INFORMED CONSENT; BREAST-CANCER; TYROSINE KINASE; QUALITY; PARTICIPATION; EUTHANASIA; INHIBITOR; ATTITUDES AB Background. Many research subjects believe incorrectly that the primary purpose of clinical trials is to benefit the-participants rather than to improve therapy for future patients. However, few data are available about how physicians view trials. Methods: We mailed surveys to a stratified random sample (n = 1120) of U.S. medical, pediatric, and other oncology specialists who were selected from the American Society of Clinical Oncology Membership Directory. Respondents were asked to select, from a list of options, their reasons for enrolling individual patients in trials and what they thought the main societal purposes of clinical trials are. We used logistic regression models to evaluate which demographic and clinical practice characteristics were associated with responses to these questions. All statistical tests were two-sided. Results: Of the 547 physicians (48.8%) who responded, 40.5% of the medical oncologists, 32.3% of the pediatric oncologists, and 62.6% of the other oncology subspecialists reported enrolling individual patients in clinical trials to improve future therapy. Most of the other respondents reported enrolling patients to ensure that they received state-of-the-art treatment. When asked about the main societal purpose of clinical trials, 72.7% of the medical oncologists, 59.4% of the pediatric oncologists, and 81.9% of the other oncology subspecialists cited improving future therapy; most of the other respondents cited ensuring state-of-the-art treatment for participants. In multivariable analysis, medical oncologists (odds ratio [OR] = 0.6, 95% confidence interval [CI] = 0.3 to 0.9) and pediatric oncologists (OR = 0.3, 95% CI = 0.2 to 0.5) were less likely than other oncologists to identify improving future therapy as the main societal purpose of clinical trials, whereas industry physicians (OR = 4.6, 95 % CI = 1.1 to 20.5) chose this option more often than physicians who did not work for industry. Conclusions: Many respondents viewed the main societal purpose of clinical trials as benefiting the participants rather than as creating generalizable knowledge to advance future therapy. This view, which was more prevalent among specialists such as pediatric oncologists that enrolled greater proportions of patients in trials, conflicts with established principles of research ethics. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Pediat Oncol, 454 BRK Suite 21,44 Binney St, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 FU NHLBI NIH HHS [T32 HL07574-19] NR 40 TC 67 Z9 68 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 18 PY 2002 VL 94 IS 24 BP 1847 EP 1853 PG 7 WC Oncology SC Oncology GA 625PQ UT WOS:000179825200010 PM 12488478 ER PT J AU Guo, L Zhang, ZQ Green, K Stanton, RC AF Guo, L Zhang, ZQ Green, K Stanton, RC TI Suppression of interleukin-1 beta-induced nitric oxide production in RINm5F cells by inhibition of glucose-6-phosphate dehydrogenase SO BIOCHEMISTRY LA English DT Article ID PANCREATIC BETA-CELLS; INSULIN-PRODUCING CELLS; RAT ISLETS; SYNTHASE; LANGERHANS; EXPRESSION; SECRETION; CYTOKINES; RELEASE; MACROPHAGES AB In rat pancreatic islets and insulin-producing cell lines, IL-1beta induces expression of inducible nitric oxide synthase and NO production leading to impairment of glucose-stimulated insulin release and decreased cell survival. NADPH is an obligatory cosubstrate for iNOS synthesis of NO. We hypothesized that IL-1beta stimulates an increase in activity of NADPH-producing enzyme(s) prior to NO production and that this increase is necessary for NO production. Using rat insulin-secreting RINm5F cells, we found that (1) IL-1beta caused a biphasic change in the NADPH level (increased by 6 h and decreased after prolonged incubation in the presence of 2 ng/mL IL-1beta); (2) IL-1beta stimulated increased activity of glucose-6-phosphate dehydrogenase (G6PD) in a time- and dose-dependent manner, and G6PD expression was increased by about 80% after exposure to 2 ng/mL IL-1beta for 18 h: (3) IL-1beta-stimulated NO production was positively correlated with increased G6PD activity; (4) IL-1beta did not cause any significant change in enzyme activity of another NADPH-producing enzyme, malic enzyme; (5) IL-1beta-induced NO production was significantly reduced either by inhibiting G6PD activity using an inhibitor of G6PD (dehydroepiandrosterone) or by inhibiting G6PD expression using an antisense oligonucleotide to G6PD mRNA; and (6) IL-1beta stimulated a decrease in the cAMP level. 8-Bromo-cAMP caused decreased G6PD activity, and the protein kinase A inhibitor H89 led to a increase in G6PD activity in RINm5F cells. In conclusion, our data show that IL-1beta stimulated G6PD activity and expression level, providing NADPH that is required by iNOS for NO production in RINm5F cells. Also, inhibition of the cAMP-dependent PKA signal pathway is involved in an IL-1beta-stimulated increase in G6PD activity. C1 Joslin Diabet Ctr, Vasc Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Vasc Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-54380] NR 46 TC 16 Z9 17 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 17 PY 2002 VL 41 IS 50 BP 14726 EP 14733 DI 10.1021/bi026110v PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 625LD UT WOS:000179817200011 PM 12475221 ER PT J AU Hallen, S Bjorquist, A Ostlund-Lindqvist, AM Sachs, G AF Hallen, S Bjorquist, A Ostlund-Lindqvist, AM Sachs, G TI Identification of a region of the ileal-type sodium/bile acid cotransporter interacting with a competitive bile acid transport inhibitor SO BIOCHEMISTRY LA English DT Article ID CORONARY HEART-DISEASE; SUBSTRATE-SPECIFICITY; HYPERLIPIDEMIAS POSCH; FUNCTIONAL EXPRESSION; SURGICAL CONTROL; CLONING; RABBIT; BYPASS; GENE; HYPERCHOLESTEROLEMIA AB Drug intervention that prevents reabsorption of circulating bile acids by the apical (ileal) sodium/bile acid cotransporter (ASBT) may be a promising new therapy for lowering of plasma cholesterol. 2164U90 is a benzothiazepine-based competitive inhibitor of bile acid transport with K-i values of similar to10 and 0.068 muM for the homologous human and mouse apical transporters, respectively. Hybrid human-mouse and mouse-human transporters were engineered to identify regions involved in this 150-fold difference in the inhibition constant for 2164U90. A mouse-human chimera with only the most C-terminal hydrophobic domain and the C-terminus of the transporter originating from the human variant was found to have a sensitivity to 2164U90 inhibition similar to that of the human transporter. Conversely, a human-mouse hybrid transporter encompassing the same C-terminal region from the mouse sequence but now inserted into the human sequence demonstrated the greater inhibition seen with the mouse wild type ASBT. Amino acid substitutions, individually or in combinations, of six candidate nonconserved residues between mouse and human transporters in this C-terminal domain showed replacements of Thr294 by Ser and Val295 by Ile to be responsible for the difference in the sensitivity toward 2164U90 seen between the species. The hamster apical SBAT encompassing Ser/Ile in these positions shared the lower sensitivity to 2164U90, as seen with the human ASBT, even though it is identical to the mouse SBAT in the remaining four positions of this region. In addition, the rat ASBT which is identical to the mouse ASBT in this domain also had the high sensitivity to 2164U90 inhibition found for the mouse ASBT. Methanethio-sulfonates (MTS) are known to inactivate the sodium/bile acid transporters through alkylation of a cysteine in the most C-terminal hydrophobic domain (1). Inactivation of the human ASBT due to MTS modification of cysteine 270 was shown to be largely abolished when the transporter was preincubated with 2164U90, suggesting that the binding of this benzothiazepine is in the vicinity of position 270. Thus, the domain containing the two most C-terminal putative transmembrane regions of the SBATs, H8-H9, previously shown to constitute part of the binding pocket for bile acids, interacts also with the bile acid transport competitive inhibitor, 2164U90. C1 Univ Calif Los Angeles, Los Angeles, CA 90073 USA. Wadsworth Vet Adm Hosp, Los Angeles, CA 90073 USA. AstraZeneca, R&D, Molndal, Sweden. RP Sachs, G (reprint author), W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK41301, DK53462, DK46917, DK17294] NR 31 TC 24 Z9 25 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 17 PY 2002 VL 41 IS 50 BP 14916 EP 14924 DI 10.1021/bi0205404 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 625LD UT WOS:000179817200030 PM 12475240 ER PT J AU Endoh, M Ogawa, M Orkin, S Nishikawa, S AF Endoh, M Ogawa, M Orkin, S Nishikawa, S TI SCL/tal-1-dependent process determines a competence to select the definitive hematopoietic lineage prior to endothelial differentiation SO EMBO JOURNAL LA English DT Article DE ES cell; FLK1; MerCreMer; SCL; tal-1; VE-cadherin ID EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTOR; IN-VITRO; LYMPHOHEMATOPOIETIC CELLS; PRIMITIVE ERYTHROPOIESIS; GENE-EXPRESSION; SCL GENE; SCL/TAL-1; MESODERM; MICE AB Hematopoiesis in most vertebrate species occurs in two distinct phases, primitive and definitive, which diverge from FLK1(+)VE-cadherin(-) mesoderm and FLK1(+)VE-cadherin(+) endothelial cells (EC), respectively. This study aimed at determining the stage at which hematopoietic lineage fate is determined by manipulating the SCL/tal-1 expression that is known to be essential for the early development of the primitive and definitive hematopoietic systems. We established SCL-null ES cell lines in which SCL expression is rescued by tamoxifen-inducible Cre recombinase-loxP site-mediated recombination. While no hematopoietic cells (HPC) were detected in SCL-null ES cell differentiation cultures, SCL gene reactivation from day 2 to day 4 after initiation of differentiation could rescue both primitive and definitive hematopoiesis. SCL reactivation at later phases was ineffective. Moreover, generation of VE-cadherin(+) EC that can give rise to definitive HPC required SCL reactivation prior to VE-cadherin expression. These results indicated that the competence to become HPC is acquired at the mesodermal stage by a SCL-dependent process that takes place independently of determination of endothelial fate. C1 Kyoto Univ, Grad Sch Med, Dept Mol Genet, Kyoto 6068057, Japan. Kumamoto Univ, Inst Mol Embryol & Genet, Dept Cell Differentiat, Kumamoto 8600811, Japan. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. RP Endoh, M (reprint author), Kyoto Univ, Grad Sch Med, Dept Mol Genet, Kyoto 6068057, Japan. FU NCIPC CDC HHS [U17 CE002005] NR 31 TC 58 Z9 60 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 16 PY 2002 VL 21 IS 24 BP 6700 EP 6708 DI 10.1093/emboj/cdf674 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 627TJ UT WOS:000179952000008 PM 12485991 ER PT J AU Bres, V Tagami, H Peloponese, JM Loret, E Jeang, KT Nakatani, Y Emiliani, S Benkirane, M Kiernan, RE AF Bres, V Tagami, H Peloponese, JM Loret, E Jeang, KT Nakatani, Y Emiliani, S Benkirane, M Kiernan, RE TI Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF SO EMBO JOURNAL LA English DT Article DE cyclin T1; differential acetylation; HIV-1; PCAF; Tat ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA-POLYMERASE-II; HISTONE ACETYLTRANSFERASE ACTIVITY; TRANSCRIPTIONAL COACTIVATORS P300; PROTEINS SPECIFICALLY ASSOCIATE; CARBOXYL-TERMINAL DOMAIN; CREB-BINDING-PROTEIN; HIV-1 TAT; P-TEFB; IN-VITRO AB The HIV-1 transactivator protein, Tat, is an atypical transcriptional activator that functions through binding, not to DNA, but to a short leader RNA, TAR. Although details of its functional mechanism are still unknown, emerging findings suggest that Tat serves primarily to adapt co-activator complexes such as p300, PCAF and P-TEFb to the HIV-1 long terminal repeat. Hence, an understanding of how Tat interacts with these cofactors is crucial. It has recently been shown that acetylation at a single lysine, residue 50, regulated the association of Tat with PCAF. Here, we report that in the absence of Tat acetylation, PCAF binds to amino acids 20-40 within Tat. Interestingly, acetylation of Tat at Lys28 abrogates Tat-PCAF interaction. Acetylation at Lys50 creates a new site for binding to PCAF and dictates the formation of a ternary complex of Tat-PCAF-P-TEFb. Thus, differential lysine acetylation of Tat coordinates the interactions with its co-activators, cyclin T1 and PCAF. Our results may help in understanding the ordered recruitment of Tat co-activators to the HIV-1 promoter. C1 CNRS, UPR 1142, Inst Genet Humaine, Lab Virol Mol & Transfert Gene, Montpellier, France. CNRS, UPR 9027, Inst Biol Struct & Microbiol, Lab Ingn Syst Macromol, Marseille, France. Inst Cochin, Dept Malad Infect, Paris, France. NIAID, Mol Virol Lab, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Res Ctr, Boston, MA USA. RP Kiernan, RE (reprint author), CNRS, UPR 1142, Inst Genet Humaine, Lab Virol Mol & Transfert Gene, Montpellier, France. RI Jeang, Kuan-Teh/A-2424-2008 NR 54 TC 69 Z9 72 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 16 PY 2002 VL 21 IS 24 BP 6811 EP 6819 DI 10.1093/emboj/cdf669 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 627TJ UT WOS:000179952000019 PM 12486002 ER PT J AU Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Corey, D Levy, D AF Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Corey, D Levy, D TI Genome scan linkage results for heart rate variability (The Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB There is a substantial heritable component to the beat-to-beat variation in heart rate. However, the molecular mechanisms underlying the control of heart rate variability (HRV) remain unknown. The present study sought to identify chromosomal regions linked to HRV phenotypes. The first 2 hours of ambulatory electrocardiographic recordings obtained from Framingham Heart Study subjects attending a routine examination were processed for HRV. HRV variables analyzed included very-low-frequency power, low-frequency power, and high-frequency power. Gender-specific residuals were used for log-transformed HRV data after adjustment for age, HR, systolic and diastolic blood pressures, and coffee and alcohol consumption. In conjunction with a 16-cM genome-wide scan, HRV data were available for 725 subjects in 230 extended families, including 390 sibling pairs. Variance component log-of-the-odds (LOD) scores were obtained. The highest multipoint LOD score's were obtained for log very-low frequency on chromosome 15 at 62 cM (LOD 1.84) and for log low frequency on chromosome 2 at 153 cM (LOD 1.81). These data suggest there may be influential genetic regions contributing to HRV. Further studies are warranted to identify genes in these regions that may influence autonomic tone. Recognition of the genetic determinants of HRV may provide additional insights into the pathophysiology of the autonomic nervous system and offer clues to its modulation. (C) 2002 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayne Ave,Suite 2, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-38038] NR 23 TC 27 Z9 27 U1 0 U2 2 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 DEC 15 PY 2002 VL 90 IS 12 BP 1290 EP 1293 AR PII S0002-9149(02)02865-5 DI 10.1016/S0002-9149(02)02865-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 628PD UT WOS:000180004000003 PM 12480036 ER PT J AU Kramer, BJ Harker, JO Wong, AL AF Kramer, BJ Harker, JO Wong, AL TI Arthritis beliefs and self-care in an urban American Indian population SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE Native Americans; joint pain; self-care; education; health beliefs; coping ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; COPING STRATEGIES; HIGH PREVALENCE; PAIN PATIENTS; DISEASE; DISABILITY; ALCOHOL; HEALTH AB Objective. To describe beliefs and self-care strategies of American Indians with chronic arthritis joint pain. Method. In-depth interviews were conducted with a convenience sample of urban-dwelling American Indians (n = 56) concerning self-care and beliefs about arthritis; objective measures of arthritis disease activity were obtained through standardized interview protocols. Results. Joint pain was not generally assumed to be arthritis nor directly related to aging. Belief that chronic pain affecting multiple joints was a serious and unexpected condition oriented American Indians' decisions to seek medical attention. However, verbal communications about pain may be subtle or under emphasized. Few coping strategies were used to control either chronic or episodic pain. Conclusions. Chronic arthritis pain may not be optimally managed in this population. Cultural assessment should recognize that American Indian patients may understate serious symptoms. Community educational interventions should target this population to enhance self-care, pain management, and communication of arthritis symptoms to physicians. C1 Dept Vet Affairs Greater Los Angeles Healthcare S, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. RP Kramer, BJ (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr 11E, Sepulveda Ambulatory Care Ctr & Nursing Home, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 28 TC 18 Z9 18 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 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD DEC 15 PY 2002 VL 47 IS 6 BP 588 EP 594 DI 10.1002/art.10795 PG 7 WC Rheumatology SC Rheumatology GA 624ZG UT WOS:000179791700004 PM 12522831 ER PT J AU Mitropoulou, V Harvey, PD Maldari, LA Moriarty, PJ New, AS Silverman, JM Siever, LJ AF Mitropoulou, V Harvey, PD Maldari, LA Moriarty, PJ New, AS Silverman, JM Siever, LJ TI Neuropsychological performance in schizotypal personality disorder: Evidence regarding diagnostic specificity SO BIOLOGICAL PSYCHIATRY LA English DT Article DE information processing; cognition; memory; learning; schizophrenia spectrum ID VISUOSPATIAL WORKING-MEMORY; SCHIZOPHRENIC-PATIENTS; NONPSYCHOTIC RELATIVES; SEX-DIFFERENCES; PERSPECTIVE; INHIBITION; DEFICITS; TASK; PEN AB Background: Individuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS). Methods: We tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color-Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV-R), and the Wechsler Adult Intelligence Scale vocabulary and block design. Results: Normative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV-R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV-R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score (r = -.32, p < .006). Conclusions: Compared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV-R immediate and delayed recall (a learning-recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia. (C) 2002 Society of Biological Psychiatry. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, New York, NY USA. VA VISN 3 MIRECC, New York, NY USA. RP Mitropoulou, V (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, Box 1027,1 Gustave Levy Pl, New York, NY 10029 USA. FU NCRR NIH HHS [NCRR-MO1-RR00071]; NIMH NIH HHS [R01-MH 5606] NR 44 TC 47 Z9 47 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2002 VL 52 IS 12 BP 1175 EP 1182 AR PII S0006-3223(02)01426-9 DI 10.1016/S0006-3223(02)01426-9 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 634QW UT WOS:000180352800007 PM 12488063 ER PT J AU Tallman, MS Andersen, JW Schiffer, CA Appelbaum, FR Feusner, JH Woods, WG Ogden, A Weinstein, H Shepherd, L Willman, C Bloomfield, CD Rowe, JM Wiernik, PH AF Tallman, MS Andersen, JW Schiffer, CA Appelbaum, FR Feusner, JH Woods, WG Ogden, A Weinstein, H Shepherd, L Willman, C Bloomfield, CD Rowe, JM Wiernik, PH TI All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol SO BLOOD LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Hematology CY DEC 03-08, 1999 CL NEW ORLEANS, LA SP Amer Soc Hematol ID ACUTE MYELOID-LEUKEMIA; ARSENIC TRIOXIDE; P-GLYCOPROTEIN; MOLECULAR REMISSION; TRANSRETINOIC ACID; CD56 EXPRESSION; FOLLOW-UP; THERAPY; CHEMOTHERAPY; RELAPSE AB We previously reported a benefit for all-trans retinoic acid (ATRA) in both induction and maintenance therapy in patients with acute promyelocytic leukemia (APL). To determine the durability of this benefit and identify important prognostic factors, long-term follow-up of the North American Intergroup APL trial is reported. A total of 350 patients with newly diagnosed APL were randomized to either daunorubicin and cytarabine (DA) or ATRA for induction and then either ATRA maintenance or observation following consolidation chemotherapy. The complete remission (CR) rates were not significantly different between the ATRA and DA groups (70% and 73%, respectively). However, the 5-year disease-free survival (DFS) and overall survival (OS) were longer with ATRA than with DA for induction (69% vs 29% and 69% vs 45%, respectively). Based on both induction and maintenance randomizations, the 5-year DFS was 16% for patients randomized to DA and observation, 47% for DA and ATRA, 55% for ATRA and observation, and 74% for ATRA and ATRA. There was no advantage of either induction regimen among any subgroups when CR alone was considered. However, female sex, classical M3 morphology (vs the microgranular variant [M3v]), and treatment-white blood cell count (WBC) interaction (ATRA/WBC below 2 x 10(9)/L [2000/muL] best, DA/WBC above 2 x 10(9)/L worst) were each significantly associated with improved DFS (P<.05). Treatment with ATRA, WBC below 2 x 10(9)/L, and absence of bleeding disorder were each significantly associated with improved OS. Age more than 15 years, female sex, and treatment-morphology interaction (DA/M3v worst, ATRA best regardless of morphology) were each significantly associated with improved DFS based on maintenance randomization. The improvement in outcome with ATRA in APL was maintained with long-term follow-up. C1 Northwestern Univ, Feinburg Sch Med, Dept Med,Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Eastern Cooperat Oncol Grp, Brookline, MA USA. Harvard Univ, Sch Publ Hlth, ECOG, Boston, MA 02115 USA. Wayne State Univ, Karmanos Canc Ctr, Detroit, MI USA. Canc & Leukemia Grp B, Chicago, IL USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. SW Oncol Grp, San Antonio, TX USA. Childrens Hosp No Calif Oakland, Oakland, CA USA. Emory Univ, Childrens Healthcare, Atlanta, GA 30322 USA. Texas Childrens Canc Ctr, Houston, TX USA. Pediat Oncol Grp, Chicago, IL USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, POG, Boston, MA USA. Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada. Univ New Mexico, SWOG, Albuquerque, NM 87131 USA. Ohio State Univ, CALGB, Columbus, OH 43210 USA. Technion Israel Inst Technol, Rambam Med Ctr, ECOG, Haifa, Israel. New York Med Coll, Our Lady Mercy Canc Ctr, ECOG, Bronx, NY USA. RP Northwestern Univ, Feinburg Sch Med, Dept Med,Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, 676 N St Clair St,Suite 850, Chicago, IL 60611 USA. EM m-tallman@northwestern.edu FU NCI NIH HHS [CA31946, CA03161, CA11083, CA14958, CA16058, CA17145, CA20319, CA21115, CA23318, CA31983, CA32102, CA37027, CA66636, CA77658] NR 40 TC 256 Z9 276 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 15 PY 2002 VL 100 IS 13 BP 4298 EP 4302 DI 10.1182/blood-2002-02-0632 PG 5 WC Hematology SC Hematology GA 624KX UT WOS:000179759800011 PM 12393590 ER PT J AU Byrd, JC Mrozek, K Dodge, RK Carroll, AJ Edwards, CG Arthur, DC Pettenati, MJ Patil, SR Rao, KW Watson, MS Koduru, PRK Moore, JO Stone, RM Mayer, RJ Feldman, EJ Davey, FR Schiffer, CA Larson, RA Bloomfield, CD AF Byrd, JC Mrozek, K Dodge, RK Carroll, AJ Edwards, CG Arthur, DC Pettenati, MJ Patil, SR Rao, KW Watson, MS Koduru, PRK Moore, JO Stone, RM Mayer, RJ Feldman, EJ Davey, FR Schiffer, CA Larson, RA Bloomfield, CD TI Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461) SO BLOOD LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Hematology CY DEC 07-11, 2001 CL ORLANDO, FLORIDA SP Amer Soc Hematol ID ACUTE PROMYELOCYTIC LEUKEMIA; INTENSIVE POSTREMISSION CHEMOTHERAPY; ACUTE NONLYMPHOCYTIC LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; HIGH-DOSE CYTARABINE; TRANS-RETINOIC ACID; POOR-PROGNOSIS; CLINICAL-SIGNIFICANCE AB We analyzed prospectively 1213 adults with de novo acute myeloid leukemia (AML) to ascertain the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, 5-year cumulative incidence of relapse (CIR), and 5-year overall survival (OS). All patients received similar induction therapy. Median follow-up for surviving patients was 8.3 years. Nonprioritized cytogenetics distinguished t(8;21) and inv(16)/t(16;16) as conferring a significantly better prognosis than normal karyotype. Prognostic impact of many abnormalities could not be determined independently because of their association with complex karyotype. Neither complex karyotype nor secondary aberrations affected outcome of patients with t(8;21), inv(16)/t(16;16), or t(9;11). Among other patients, those with complex karyotypes had significantly worse outcomes than cytogenetically normal patients. Based on outcome for specific cytogenetic abnormalities and karyotype complexity, patients were divided into 3 risk groups: favorable (CR 88%, CIR 54%, OS 55%), intermediate (CR 67%, CIR 67%, OS 24%), and adverse (CR 32%, CIR 92%, OS 5%). Multivariate analyses confirmed the major contribution of cytogenetics to the probability of attaining CR, CIR, and OS. For the adverse-risk group, the probability of achieving CR was 4.0 and 11.9 times lower, the probability of relapse 3.0 and 4.4 times higher, and the risk of death 2711 and 4.3 times higher than those for the intermediate and favorable groups, respectively. We conclude that although the prognostic impact of many recurring abnormalities has not been ascertained independently of complex karyotype, cytogenetics is among the most useful factors predicting attainment of CR, CIR, and long-term survival in adult AML. C1 Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA. CALGB Stat Ctr, Durham, NC USA. Univ Alabama, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. Wake Forest Univ, Med Ctr, Winston Salem, NC USA. Univ Iowa, Iowa City, IA USA. Univ N Carolina, Chapel Hill, NC USA. Washington Univ, St Louis, MO USA. N Shore Univ Hosp, Manhasset, NY USA. Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, New York, NY USA. SUNY Upstate Med Univ, Syracuse, NY USA. Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. Univ Chicago, Chicago, IL 60637 USA. RP Byrd, JC (reprint author), Ohio State Univ, Div Hematol & Oncol, B302A Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA 77658, CA16058, CA31946] NR 59 TC 939 Z9 1007 U1 1 U2 11 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 DEC 15 PY 2002 VL 100 IS 13 BP 4325 EP 4336 DI 10.1182/blood-2002-03-0772 PG 12 WC Hematology SC Hematology GA 624KX UT WOS:000179759800015 PM 12393746 ER PT J AU Richardson, PG Murakami, C Jin, ZZ Warren, D Momtaz, P Hoppensteadt, D Elias, AD Antin, JH Soiffer, R Spitzer, T Avigan, D Bearman, SI Martin, PL Kurtzberg, J Vredenburgh, J Chen, AR Arai, S Vogelsang, G McDonald, GB Guinan, EC AF Richardson, PG Murakami, C Jin, ZZ Warren, D Momtaz, P Hoppensteadt, D Elias, AD Antin, JH Soiffer, R Spitzer, T Avigan, D Bearman, SI Martin, PL Kurtzberg, J Vredenburgh, J Chen, AR Arai, S Vogelsang, G McDonald, GB Guinan, EC TI Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE RENAL-FAILURE; VENOCCLUSIVE DISEASE; ANTITHROMBOTIC AGENT; COMPASSIONATE-USE; LIVER; DIAGNOSIS; THERAPY AB Veno-occlusive disease (VOD) is the most common regimen-related toxicity accompanying stem cell transplantation (SCT). Severe VOD complicated by multisystem organ failure (MOF) remains almost uniformly fatal. Preliminary experience with defibrotide (DF), a single-stranded polydeoxyribonucleotide with fibrinolytic, antithrombotic, and anti-ischemic properties, in the treatment for severe VOD has suggested safety and activity. Eighty-eight patients who developed severe VOD after SCT were treated with DF under a defined treatment plan. At diagnosis, median bilirubin was 76.95 muM (4.5 mg/dL), present in 84%, and abnormal hepatic portal venous flow was present in 35%. At DF initiation, median bilirubin had increased to 215.46 muM (12.6 mg/dL), and MOF was present in 97%. DF was administered intravenously in doses ranging from 5 to 60 mg/kg per day for a median of 15 days. No severe hemorrhage or other serious toxicity related to DF was reported. Complete resolution of VOD was seen in 36%, with 35% survival at day +100. Predictors of survival included younger age, autologous SCT, and abnormal portal flow, whereas busulfan-based conditioning and encephalopathy predicted worse outcome. Decreases in mean creatinine and plasminogen activator inhibitor 1(PAI-1) levels during DF therapy predicted better survival. The complete response rate, survival to day +100, and absence of significant DF-associated toxicity in this largest patient cohort reported to date confirm the results of earlier studies. Certain features associated with successful outcome may correlate with DF-related treatment effects, and prospective evaluation of DF therapy for severe VOID should allow better definition of predictors of response or failure. C1 Dana Farber Canc Inst, Dept Adult & Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Adult & Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Hosp,Massachusetts Gen Hosp, Childrens Hosp,Div Hematol Oncol, Boston, MA USA. Columbia Univ, New York, NY USA. Loyola Univ, Med Ctr, Chicago, IL 60611 USA. Univ Colorado, Ctr Hlth, Denver, CO 80202 USA. Duke Univ, Med Ctr, Durham, NC USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Dept Adult & Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 55 TC 165 Z9 177 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2002 VL 100 IS 13 BP 4337 EP 4343 DI 10.1182/blood-2002-04-1216 PG 7 WC Hematology SC Hematology GA 624KX UT WOS:000179759800016 PM 12393437 ER PT J AU DiNubile, MJ Stossel, TP Ljunghusen, OC Ferrera, JLM Antin, JH AF DiNubile, MJ Stossel, TP Ljunghusen, OC Ferrera, JLM Antin, JH TI Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; IDIOPATHIC-PNEUMONIA-SYNDROME; RESPIRATORY-DISTRESS-SYNDROME; D-BINDING PROTEIN; LUNG INJURY; INTERSTITIAL PNEUMONITIS; LYSOPHOSPHATIDIC ACID; SCAVENGER SYSTEM; GROWTH-FACTOR; ACTIN AB The idiopathic pneumonia syndrome (IPS) represents a common and often fatal complication of hematopoietic stem cell transplantation (HSCT). Gelsolin is a highly conserved actin-binding protein normally present in plasma that may serve a basic physiological role in limiting acute lung injury of diverse etiologies. We hypothesized that depletion of circulating gelsolin following HSCT might play a permissive role in the pathogenesis of IPS. Plasma gelsolin levels were measured by immunoblotting in frozen samples obtained weekly from 24 patients undergoing allogeneic HSCT. Patients with and without IPS were similar with respect to age, diagnosis, histocompatibility differences between donor and recipient, and conditioning regimen. Mean gelsolin levels in the 9 patients with rapidly fatal IPS were significantly lower than those in patients without this complication by week 3 after HSCT (1101 +/- 61 mg/L versus 221 +/- 54 mg/L; P = .0002). Seven (88%) of the 8 patients with gelsolin levels of less than 100 mg/L in the first month after HSCT died from IPS within 3 months; conversely, gelsolin levels fell to less than 100 mg/L in 7 (78%) of the 9 patients who died from IPS within 3 months of HSCT (P = .0007). These findings suggest that gelsolin levels shortly after allogeneic HSCT can predict the later development of fatal IPS. Gelsolin replacement in selected transplant patients may offer a novel strategy to prevent or reverse IPS. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Infect Dis, Camden, NJ 08103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Hematol Oncol, Camden, NJ 08103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Expt Med, Camden, NJ 08103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Camden, NJ 08103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Cooper Hlth Syst, Camden, NJ 08103 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP DiNubile, MJ (reprint author), Merck Res Labs, POB 4,BL3-4, W Point, PA 19486 USA. NR 33 TC 41 Z9 43 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2002 VL 100 IS 13 BP 4367 EP 4371 DI 10.1182/blood-2002-06-1672 PG 5 WC Hematology SC Hematology GA 624KX UT WOS:000179759800020 PM 12393536 ER PT J AU Radomska, HS Gonzalez, DA Okuno, Y Iwasaki, H Nagy, A Akashi, K Tenen, DG Huettner, CS AF Radomska, HS Gonzalez, DA Okuno, Y Iwasaki, H Nagy, A Akashi, K Tenen, DG Huettner, CS TI Transgenic targeting with regulatory elements of the human CD34 gene SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; LOCUS-CONTROL REGION; MONOCLONAL-ANTIBODY; PROGENITOR CELLS; MESSENGER-RNA; MURINE CD34; BONE-MARROW; IN-VIVO; MAMMALIAN-CELLS; HIGH-LEVEL AB The human CD34 gene is expressed on early progenitor and stem cells in the bone marrow. Here we report the isolation of the human CD34 locus from a human 131 artificial chromosome (PAC) library and the characterization and evaluation of this genomic fragment for expression of reporter genes in stable cell lines and transgenic mice. We show that a 160-kb fragment spanning 110 kb of the 5' flanking region and 26 kb of the 3' flanking region of the CD34 gene directs expression of the human CD34 gene in the bone marrow of transgenic mice. The expression of human CD34 transgenic RNA in tissues was found to be similar to that of the endogenous murine CD34 gene. Colony-forming cell assays showed that bone marrow cells staining positive for human CD34 consist of early progenitor cells in which expression of CD34 decreased with cell maturation. In order to test the construct for its ability to express heterologous genes in vivo, we used homologous recombination in bacteria to insert the tetracycline-responsive transactivator protein tTA. Analysis of transgenic human CD34-tTA mice by cross breeding with a strain carrying Cre recombinase under control of a tetracycline-responsive element demonstrated induction of Cre expression in mice in a pattern consistent with the expression of the human CD34 transgene. C1 Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Radomska, HS (reprint author), Harvard Univ, Sch Med, Harvard Inst Med, Room 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Nagy, Andras/G-6465-2013; OI Tenen, Daniel/0000-0002-6423-3888 FU NIDDK NIH HHS [DK48660] NR 63 TC 34 Z9 36 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 DEC 15 PY 2002 VL 100 IS 13 BP 4410 EP 4419 DI 10.1182/blood-2002-02-0355 PG 10 WC Hematology SC Hematology GA 624KX UT WOS:000179759800025 PM 12393582 ER PT J AU Okuno, Y Huettner, CS Radomska, HS Petkova, V Iwasaki, H Akashi, K Tenen, DG AF Okuno, Y Huettner, CS Radomska, HS Petkova, V Iwasaki, H Akashi, K Tenen, DG TI Distal elements are critical for human CD34 expression in vivo SO BLOOD LA English DT Article ID STEM-CELL ANTIGEN; HIGH-LEVEL EXPRESSION; TRANSGENIC MICE; HEMATOPOIETIC PROGENITOR; GENE-EXPRESSION; C-MYB; MYELOID CELLS; ENCODING CD34; GLOBIN GENES; MURINE CD34 AB The elements regulating gene expression in hematopoietic stem cells are still poorly understood. We previously reported that a 141-kilobase (kb) human CD34 transgene confers properly regulated human CD34 expression in transgenic mice. A construct with only the human CD34 promoter and 3' enhancer region is not sufficient, suggesting that critical distal elements are necessary for expression of the human CD34 gene. To further localize such elements, we analyzed deletion constructs of the human CD34 gene and evaluated their function in transgenic mice. Constructs harboring as little as 18 kb of 5' and 26 kb of 3' human CD34 flanking sequence conferred human expression in tissues of transgenic mice with a pattern similar to that of the 141-kb human transgene. In contrast, a construct harboring 10 kb of 5' and 17 kb of 3' human CD34 flanking sequence gave no expression. These data demonstrate that regions between 16 to 18 kb upstream and/or 17 to 26 kb downstream of the human CD34 gene contain critical elements for human CD34 expression in vivo. Further functional analysis, of these regions in transgenic mite will be crucial for understanding CD34 gene expression in hematopoietic stem and progenitor cells. C1 Harvard Inst Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. RP Tenen, DG (reprint author), Harvard Inst Med, Div Hematol Oncol, Rm 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. OI Tenen, Daniel/0000-0002-6423-3888 FU NIDDK NIH HHS [DK48660] NR 42 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2002 VL 100 IS 13 BP 4420 EP 4426 DI 10.1182/blood-2002-03-0788 PG 7 WC Hematology SC Hematology GA 624KX UT WOS:000179759800026 PM 12393741 ER PT J AU Shimamura, A Oca, RMC Svenson, JL Haining, N Moreau, LA Nathan, DG D'Andrea, AD AF Shimamura, A Oca, RMC Svenson, JL Haining, N Moreau, LA Nathan, DG D'Andrea, AD TI A novel diagnostic screen for defects in the Fanconi anemia pathway SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; SERUM-ALPHA-FETOPROTEIN; ATAXIA-TELANGIECTASIA; COMPLEMENTATION GROUP; DIEPOXYBUTANE SENSITIVITY; CHROMOSOME BREAKAGE; NUCLEAR-COMPLEX; CELL-CYCLE; GENE; CYCLOPHOSPHAMIDE AB Fanconi anemia (FA) is an autosomal recessive chromosomal instability syndrome characterized by congenital abnormalities, progressive bone marrow failure, and cancer predisposition. Although patients with FA are candidates for bone marrow transplantation or gene therapy, their phenotypic heterogeneity can delay or obscure diagnosis. The current diagnostic test for FA consists of cytogenetic quantitation of chromosomal breakage in response to diepoxybutane (DEB) or mitomycin C (MMC). Recent studies have elucidated a biochemical pathway for Fanconi anemia that culminates in the monoubiquitination of the FANCD2 protein. In the current study, we develop a new rapid diagnostic and subtyping FA assay amenable for screening broad populations at risk of FA. Primary lymphocytes were assayed for FANCD2 monoubiquitination by immunoblot. The absence of the monoubiquitinated FANCD2 isoform correlated with the diagnosis of FA by DEB testing in 11 known patients with FA, 37 patients referred for possible FA, and 29 healthy control subjects. Monoubiquitination of FANCD2 was normal in other bone marrow failure syndromes and chromosomal breakage syndromes. A combination of retroviral gene transfer and FANCD2 immunoblotting provides a rapid subtyping assay for patients newly diagnosed with FA. These new FA screening assays would allow efficient testing of broad populations at risk. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Shimamura, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01HL54785, P50 HL54785, R01HL52725] NR 57 TC 63 Z9 65 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2002 VL 100 IS 13 BP 4649 EP 4654 DI 10.1182/blood-2002-05-1399 PG 6 WC Hematology SC Hematology GA 624KX UT WOS:000179759800056 PM 12393398 ER PT J AU Mandelblatt, JS Edge, SB Meropol, NJ Senie, R Tsangaris, T Grey, L Peterson, B Hwang, YT Weeks, JC AF Mandelblatt, JS Edge, SB Meropol, NJ Senie, R Tsangaris, T Grey, L Peterson, B Hwang, YT Weeks, JC CA OPTIONS Res Team TI Sequelae of axillary lymph node dissection in older women with stage 1 and 2 breast carcinoma SO CANCER LA English DT Article DE axillary lymph node dissection; breast carcinoma; older women; arm problems ID CANCER-PATIENTS; SENTINEL LYMPHADENECTOMY; ADJUVANT CHEMOTHERAPY; ROUTINE MANAGEMENT; DECISION-ANALYSIS; ELDERLY WOMEN; WHITE WOMEN; MORBIDITY; RISK; AGE AB BACKGROUND. There are few data on the long-term sequelae of axillary dissection among older breast carcinoma patients. We describe the impact of axillary dissection in a cohort of older women. METHODS. A longitudinal cohort of 571 patients with Stage I and 2 breast carcinoma, 67 years and older, diagnosed between 1995 and 1997 from 29 hospitals in five regions, and followed for 2 years. Data were collected from patients and medical charts. The primary outcome was posttreatment quality of life. Generalized estimation equation longitudinal modeling was used to evaluate the outcome, controlling for baseline function, comorbidity, age, clinical status, and other factors. RESULTS. Sixty percent of women reported arm problems at some time in the 2 years after surgery. The cumulative risk of having arm problems 2 years posttreatment was three times higher (95% confidence interval 1.94-4.67) for women who under-went axillary surgery compared with women without axillary surgery, controlling for covariates. The effects of having axillary dissection and arthritis were multiplicative 2 years postsurgery. Arm problems were, in turn, the primary determinate of lower physical and mental functioning (P = 0.0001 and 0.04, respectively), controlling for other factors. Undergoing axillary dissection did not lessen fears about recurrence. CONCLUSIONS. Arm problems after axillary dissection have a consistent negative impact on quality of life, suggesting that the risks may outweigh the potential benefits in this population. Cancer 2002;95:2445-54. (C) 2002 American Cancer Society. C1 Georgetown Univ, Dept Oncol, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Med, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. SUNY Buffalo, Roswell Pk Canc Inst, Dept Surg, Buffalo, NY 14260 USA. Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Georgetown Univ, Dept Surg, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Sibley Mem Hosp, Dept Surg, Washington, DC USA. Beth Israel Med Ctr, Dept Surg, New York, NY 10003 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Mandelblatt, JS (reprint author), Georgetown Univ, Dept Oncol, Vincent T Lombardi Canc Res Ctr, 2233 Wisconsin Ave,Suite 317, Washington, DC 20007 USA. FU AHRQ HHS [R01 HS 08395] NR 61 TC 21 Z9 22 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2002 VL 95 IS 12 BP 2445 EP 2454 DI 10.1002/cncr.10983 PG 10 WC Oncology SC Oncology GA 622GM UT WOS:000179638700001 PM 12467056 ER PT J AU Feld, R Paesmans, M Freifeld, AG Klastersky, J Pizzo, PA Rolston, KVI Rubenstein, E Talcott, JA Walsh, TJ AF Feld, R Paesmans, M Freifeld, AG Klastersky, J Pizzo, PA Rolston, KVI Rubenstein, E Talcott, JA Walsh, TJ TI Methodology for clinical trials involving patients with cancer who have febrile neutropenia: Updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PREDICTION RULE; FEVER; CHEMOTHERAPY; THERAPY AB Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia. The guidelines suggest that response (i. e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated. Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence. Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital. Response and safety parameters should be recorded along with readmission rates. If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy. C1 Princess Margaret Hosp, Dept Hematol & Oncol, Toronto, ON M4G 2M9, Canada. Inst Jules Bordet, B-1000 Brussels, Belgium. Nebraska Med Ctr, Omaha, NE USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. MD Anderson Hoscp & Canc Ctr, Houston, TX USA. NCI, Bethesda, MD 20892 USA. RP Feld, R (reprint author), Princess Margaret Hosp, Dept Hematol & Oncol, 610 Univ Ave, Toronto, ON M4G 2M9, Canada. NR 18 TC 37 Z9 39 U1 0 U2 2 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 DEC 15 PY 2002 VL 35 IS 12 BP 1463 EP 1468 DI 10.1086/344650 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 623MM UT WOS:000179707200006 PM 12471564 ER PT J AU Laustsen, PG Michael, MD Crute, BE Cohen, SE Ueki, K Kulkarni, RN Keller, SR Lienhard, GE Kahn, CR AF Laustsen, PG Michael, MD Crute, BE Cohen, SE Ueki, K Kulkarni, RN Keller, SR Lienhard, GE Kahn, CR TI Lipoatrophic diabetes in Irs1(-/-)/Irs3(-/-) double knockout mice SO GENES & DEVELOPMENT LA English DT Article DE lipoatrophic diabetes; adipogenesis; leptin; insulin receptor substrate ID INSULIN-RECEPTOR SUBSTRATE-1; GLUCOSE-HOMEOSTASIS; TISSUE EXPRESSION; BROWN ADIPOCYTES; RESISTANCE; LEPTIN; GROWTH; GENE; DISRUPTION; MELLITUS AB Based on the phenotypes of knockout mice and cell lines, as well as pathway-specific analysis, the insulin receptor substrates IRS-1, IRS-2, IRS-3, and IRS-4 have been shown to play unique roles in insulin signal transduction. To investigate possible functional complementarity within the IRS family, we generated mice with double knockout of the genes for IRS-1/IRS-3 and IRS-1/IRS-4. Mice with a combined deficiency of IRS-1 and IRS-4 showed no differences from Irs1(-/-) mice with respect to growth and glucose homeostasis. In contrast, mice with a combined deficiency of IRS-1 and IRS-3 developed early-onset severe lipoatrophy associated with marked hyperglycemia, hyperinsulinemia, and insulin resistance. However, in contrast to other models of lipoatrophic diabetes, there was no accumulation of fat in liver or muscle. Furthermore, plasma leptin levels were markedly decreased, and adenovirus-mediated expression of leptin in liver reversed the hyperglycemia and hyperinsulinemia. The results indicate that IRS-1 and IRS-3 play important complementary roles in adipogenesis and establish the Irs1(-/-)/Irs3(-/-) double knockout mouse as a novel model of lipoatrophic diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Dartmouth Coll, Sch Med, Dept Biochem, Hanover, NH 03755 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 33201, DK 02885-K08, DK 42816, K08 DK002885, P30 DK057521, R01 DK033201, R01 DK042816, R56 DK042816] NR 28 TC 72 Z9 77 U1 2 U2 3 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 DEC 15 PY 2002 VL 16 IS 24 BP 3213 EP 3222 DI 10.1101/gad.1034802 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 632BJ UT WOS:000180203000009 PM 12502742 ER PT J AU Ciemerych, MA Kenney, AM Sicinska, E Kalaszczynska, I Bronson, RT Rowitch, DH Gardner, H Sicinski, P AF Ciemerych, MA Kenney, AM Sicinska, E Kalaszczynska, I Bronson, RT Rowitch, DH Gardner, H Sicinski, P TI Development of mice expressing a single D-type cyclin SO GENES & DEVELOPMENT LA English DT Article DE cell cycle; D-cyclins; mouse development; cell proliferation ID CELL-CYCLE; INDUCED PROLIFERATION; TRANSCRIPTION FACTOR; ESTROGEN-RECEPTOR; KINASE-ACTIVITY; CDK INHIBITORS; G1 PHASE; DIFFERENTIATION; PROGRESSION; P27(KIP1) AB D-cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery. To directly test the ability of each D-cyclin to drive development of various lineages, we generated mice expressing only cyclin D1, or only cyclin D2, or only cyclin D3. We found that these "single-cyclin" embryos develop normally until late gestation. Our analyses revealed that in single-cyclin embryos, the tissue-specific expression pattern of D-cyclins was lost. Instead, mutant embryos ubiquitously expressed the remaining D-cyclin. These findings suggest that the functions of the three D-cyclins are largely exchangeable at this stage. Later in life, single-cyclin mice displayed focused abnormalities, resulting in premature mortality. "Cyclin D1-only" mice developed severe megaloblastic anemia, "cyclin D2-only" mice presented neurological abnormalities, and "cyclin D3-only" mice lacked normal cerebella. Analyses of the affected tissues revealed that these compartments failed to sufficiently up-regulate the remaining, intact D-cyclin. In particular, we found that in cerebellar granule neuron precursors, the N-myc transcription factor communicates with the cell cycle machinery via cyclins D1 and D2, but not D3, explaining the inability of D3-only mice to up-regulate cyclin D3 in this compartment. Hence, the requirement for a particular cyclin in a given tissue is likely caused by specific transcription factors, rather than by unique properties of cyclins. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. Biogen Inc, Cambridge, MA 02142 USA. RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. OI Kalaszczynska, Ilona/0000-0001-6698-1372 FU NCI NIH HHS [1R01CA85296, R01 CA085296] NR 47 TC 194 Z9 199 U1 0 U2 2 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 DEC 15 PY 2002 VL 16 IS 24 BP 3277 EP 3289 DI 10.1101/gad.1023602 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 632BJ UT WOS:000180203000014 PM 12502747 ER PT J AU Rodriguez-Barbosa, JI Zhao, Y Zhao, GL Ezquerra, A Sykes, M AF Rodriguez-Barbosa, JI Zhao, Y Zhao, GL Ezquerra, A Sykes, M TI Murine CD4 T cells selected in a highly disparate xenogeneic porcine thymus graft do not show rapid decay in the absence of selecting MHC in the periphery SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II INTERACTION; DONOR-SPECIFIC TOLERANCE; FETAL PIG THYMUS; POSITIVE SELECTION; A-BETA; HOMEOSTATIC PROLIFERATION; NEGATIVE SELECTION; THYMECTOMIZED MICE; IN-VIVO AB CD4 repopulation can be achieved in T cell-depleted, thymectomized mice grafted with xenogeneic porcine thymus tissue. These CD4 T cells are specifically tolerant of the xenogeneic porcine thymus donor and the recipient, but are positively selected only by porcine MHC. Recent studies suggest that optimal peripheral survival of naive CD4 T cells requires the presence of the same class H MHC in the periphery as that of the thymus in which they were selected. These observations would suggest that T cells selected on porcine thymic MHC would die rapidly in the periphery, where porcine MHC is absent. Persistent CD4 reconstitution achieved in mice grafted with fetal porcine thymus might be due to increased thymic output to compensate for rapid death of T cells in the periphery. Comparison of CD4 T cell decay after removal of porcine or murine thymic grafts ruled out this possibility. No measurable role for peripheral murine class 11 MHC in maintaining the naive CD4 pool originating in thymic grafts was demonstrable. However, mouse class H MHC supported the conversion to, survival, and/or proliferation of memory-type CD4 cells selected in fetal porcine thymus. Thus, the same MHC as that mediating positive selection in the thymus is not critical for maintenance of the memory CD4 cell pool in the periphery. Our results support the interpretation that xenogeneic thymic transplantation is a feasible strategy to reconstitute CD4 T cells and render recipients tolerant of a xenogeneic donor. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, Boston, MA 02129 USA. Natl Inst Agr Res, Dept Biotechnol, Madrid, Spain. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, Massachusetts Gen Hosp E Bldg 149-5102,13th St, Boston, MA 02129 USA. RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011; Ezquerra, Angel/I-3440-2012; OI Ezquerra, Angel/0000-0002-1824-5087 FU NHLBI NIH HHS [P01 HL 18646]; NIAID NIH HHS [P01 AI139755] NR 63 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2002 VL 169 IS 12 BP 6697 EP 6710 PG 14 WC Immunology SC Immunology GA 624MN UT WOS:000179763600010 PM 12471101 ER PT J AU Chiao, CC Masland, RH AF Chiao, CC Masland, RH TI Starburst cells nondirectionally facilitate the responses of direction-selective retinal ganglion cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retina; amacrine; starburst; acetylcholine; GABA; neurotransmitters ID CHOLINERGIC AMACRINE CELLS; RABBIT RETINA; RECEPTIVE-FIELDS; SOLE ASYMMETRY; ACETYLCHOLINE; IMMUNOREACTIVITY; COMPUTATION; NEURONS; SYNAPSE; INPUT AB The mechanism of direction selectivity in retinal ganglion cells remains controversial. An important issue is how the starburst amacrine cells, which are known to provide a major synaptic input to the direction-selective ganglion cells, participate in the directional discrimination. Here, we present evidence that the cholinergic outputs of the starburst cells affect the responses of the ganglion cells symmetrically; they provide a feedforward excitation that facilitates the response of the ganglion cells to movement in both the preferred and null directions. This seems to place a constraint on models of the directional discrimination in which the starburst cells participate, namely, that their cholinergic synapses be nondirectional in their effects on the ganglion cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. NR 35 TC 36 Z9 36 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2002 VL 22 IS 24 BP 10509 EP 10513 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 626FG UT WOS:000179861100002 PM 12486140 ER PT J AU Huang, DR Tani, M Wang, JT Han, YL He, TT Weaver, J Charo, IF Tuohy, VK Rollins, BJ Ransohoff, RM AF Huang, DR Tani, M Wang, JT Han, YL He, TT Weaver, J Charo, IF Tuohy, VK Rollins, BJ Ransohoff, RM TI Pertussis toxin-induced reversible encephalopathy dependent on monocyte chernoattractant protein-1 overexpression in mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE chemokines; chemokine receptors; mice; gene targeting; macrophages; pertussis toxin ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS LESIONS; MYELIN BASIC-PROTEIN; ASTROCYTE-TARGETED EXPRESSION; DELAYED-TYPE HYPERSENSITIVITY; CHEMOKINE RECEPTOR-2 CCR2; RAT BRAIN MICROGLIA; LINE IN-VITRO AB In this report we describe pertussis toxin-induced reversible encephalopathy dependent on monocyte chemoattractant protein-1 (MCP-1) overexpression (PREMO), a novel animal model that exhibits features of human encephalopathic complications of inflammatory disorders such as viral meningoencephalitis and Lyme neuroborreliosis as well as the mild toxic encephalopathy that commonly precedes relapses of multiple sclerosis (MS). Overexpression of the mouse MCP-1 gene product (classically termed JE) in astrocytes, the major physiological CNS cellular source of MCP-1, failed to induce neurological impairment. Unexpectedly, transgenic (tg) mice overexpressing MCP-1 at a high level (MCP-1(hi)) manifested transient, severe encephalopathy with high mortality after injections of pertussis toxin (PTx) plus complete Freund's adjuvant (CFA). Surviving mice showed markedly improved function and did not relapse during a prolonged period of observation. Tg mice that expressed lower levels of MCP-1 were affected minimally after CFA/PTx injections, and tg expression of other chemokines failed to elicit this disorder. The disorder was significantly milder in mice lacking T-cells, which therefore play a deleterious role in this encephalopathic process. Disruption of CC chemokine receptor 2 (CCR2) abolished both CNS inflammation and encephalopathy, identifying CCR2 as a relevant receptor for this disorder. Proinflammatory and type 1 cytokines including TNF-alpha, IL-1beta, IFN-gamma, IL-2, RANTES, and IP-10 were elevated in CNS tissues from mice with PREMO. These studies characterize a novel model of reversible inflammatory encephalopathy that is dependent on both genetic and environmental factors. C1 Cleveland Clin Fdn, Dept Neurosci, Lerner Res Inst, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Immunol, Lerner Res Inst, Cleveland, OH 44195 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Ransohoff, RM (reprint author), Cleveland Clin Fdn, Dept Neurosci, Lerner Res Inst, NC30,9500 Euclid Ave, Cleveland, OH 44195 USA. FU NINDS NIH HHS [2R01 NS32151-09] NR 83 TC 42 Z9 44 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2002 VL 22 IS 24 BP 10633 EP 10642 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 626FG UT WOS:000179861100018 PM 12486156 ER PT J AU Maison, SF Luebke, AE Liberman, MC Zuo, J AF Maison, SF Luebke, AE Liberman, MC Zuo, J TI Efferent protection from acoustic injury is mediated via alpha 9 nicotinic acetylcholine receptors on outer hair cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE olivocochlear; nicotinic; cholinergic; noise-induced hearing loss; transgenic mouse; cochlea ID CROSSED OLIVOCOCHLEAR BUNDLE; AUDITORY-NERVE FIBERS; GUINEA-PIG COCHLEA; ELECTRICAL-STIMULATION; CAT; EXPRESSION; MICE; INNERVATION; INHIBITION; MICROSCOPY AB Exposure to intense sound can damage the mechanosensors of the inner ear and their afferent innervation. These neurosensory elements are innervated by a sound-activated feedback pathway, the olivocochlear efferent system. One major component of this system is cholinergic, and known cholinergic effects are mediated by the alpha9/alpha10 nicotinic acetylcholine receptor (nAChR) complex. Here, we show that overexpression of alpha9 nAChR in the outer hair cells of bacterial artificial chromosome transgenic mice significantly reduces acoustic injury from exposures causing either temporary or permanent damage, without changing pre-exposure cochlear sensitivity to low- or moderate-level sound. These data demonstrate that efferent protection is mediated via the alpha9 nAChR in the outer hair cells and provide direct evidence for a protective role, in vivo, of a member of the nAChR family. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Univ Miami, Sch Med, Dept Otolaryngol, Miami, FL 33136 USA. Univ Miami, Sch Med, Neurosci Program, Miami, FL 33136 USA. St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mcl@epl.meei.harvard.edu FU NCI NIH HHS [CA-21765]; NEI NIH HHS [R01 EY12950]; NIDCD NIH HHS [R03 DC-04761, P30 DC005209, R01 DC-0188, R01 DC-03086, R21 DC 05168] NR 31 TC 74 Z9 76 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 DEC 15 PY 2002 VL 22 IS 24 BP 10838 EP 10846 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 626FG UT WOS:000179861100039 PM 12486177 ER PT J AU Sandler, VM Wang, S Angelo, K Lo, HG Breakefield, XO Clapham, DE AF Sandler, VM Wang, S Angelo, K Lo, HG Breakefield, XO Clapham, DE TI Modified herpes simplex virus delivery of enhanced GFP into the central nervous system SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE herpes simplex virus; central nervous system; green fluorescent protein; gene delivery; rat CNS viral infection ID RECOMBINANT ADENOASSOCIATED VIRUS; CA1 PYRAMIDAL NEURONS; SEMLIKI-FOREST-VIRUS; GENE-TRANSFER; IN-VIVO; HIPPOCAMPAL CA1; AMPLICON VECTORS; SINDBIS VIRUS; NEURAL CELLS; MOUSE-BRAIN AB Controlled expression of proteins is a key experimental approach to a deeper understanding of the molecular basis of neuronal function. Here we evaluate the HSV-1 (herpes simplex virus) amplicon vector for gene delivery into the brains of living rats. We demonstrate that HSV-1 amplicon vectors expressing enhanced green fluorescent protein (EGFP) can reliably infect neurons after it is injected into cortex, striatum and thalamus in rats, producing sufficient numbers of infected neurons for electrophysiological experiments in acute brain slices. Expression of EGFP delivered by the HSV-1 amplicon was detected for up to 5 weeks post-infection. We detected no changes in the morphology or the electrophysiological properties of thalamic, striatal or cortical neurons within a period of at least 2 weeks after HSV-1 amplicon injection. We conclude that the HSV-1 amplicon is a valuable tool for gene delivery in the rat central nervous system. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Copenhagen, Panum Inst, DK-2200 Copenhagen, Denmark. Harvard Univ, Cambridge, MA 02138 USA. RP Clapham, DE (reprint author), Childrens Hosp, Howard Hughes Med Inst, Enders 1309,EN-306,320 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 99004]; NINDS NIH HHS [NS 24279] NR 30 TC 20 Z9 21 U1 0 U2 1 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 DEC 15 PY 2002 VL 121 IS 2 BP 211 EP 219 AR PII S0165-0270(02)00262-5 DI 10.1016/S0165-0270(02)00262-5 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 628AF UT WOS:000179968900009 PM 12468010 ER PT J AU Mileykovskiy, BY Kiyashchenko, LI Siegel, JM AF Mileykovskiy, BY Kiyashchenko, LI Siegel, JM TI Cessation of activity in red nucleus neurons during stimulation of the medial medulla in decerebrate rats SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID PONTINE RETICULAR-FORMATION; LOCUS-COERULEUS NEURONS; MUSCLE TONE SUPPRESSION; C-FOS EXPRESSION; BRAIN-STEM; RETICULOSPINAL NEURONS; RUBROSPINAL NEURONS; INHIBITORY REGIONS; LOCOMOTOR REGION; ANESTHETIZED RAT AB The Pontine oral reticular nucleus, gigantocellular reticular nucleus (Gi) and dorsal paragigantocellular nucleus (DPGi) of the medulla are key elements of a brainstem-reticulospinal inhibitory system that participates in rapid eye movement (REM) sleep atonia. Our recent study has shown that excitation of these brainstem nuclei in decerebrate rats inhibits locus coeruleus cells and the midbrain locomotor region neurons related to muscle tone facilitation. In the present study we have examined the influences of electrical and chemical stimulation of Gi and DPGi inhibitory sites on the activity of neurons located in the magnocellular part of the red nucleus (RMC), a cell group that participates in both the tonic and phasic regulation of motor output. A total of 192 RMC neurons were recorded in precollicular-premammillary decerebrate rats with muscle rigidity and induced locomotion. Thirty-three RMC neurons were identified antidromically as rubrospinal (RMC-spinal) cells by stimulation of the contralateral dorsolateral funiculus at the L2 level. A total of 141 RMC neurons (88.7%) and all RMC-spinal neurons were inhibited during electrical stimulation of Gi and DPGi inhibitory sites. This cessation of activity was correlated with bilateral muscle atonia or blockage of locomotion. Six RMC cells (3.8%) were excited (224 +/- 50%, n = 6, minimum = 98, maximum = 410, P < 0.05) and 11 cells (7%) gave no response to Gi and DPGi stimulation. Microinjections of kainic acid (100 muM, 0.2 mu1) into Gi and DPGi inhibitory sites, previously identified by electrical stimulation, produced a short-latency (35 +/- 3.5 s, n = 11) decrease of rigid hindlimb muscle tone and inhibition of all tested RMC (n = 7) and RMC-spinal (n = 5) neurons. These results, combined with our recent published data, suggest that inhibition of motor function during activation of the brainstem inhibitory system is related to both the descending inhibition of spinal motoneurons and suppression of activity in supraspinal motor facilitatory systems. These two mechanisms acting synergistically may cause generalized motor inhibition during REM sleep and cataplexy. C1 Univ Calif Los Angeles, Dept Psychiat, Sch Med, North Hills, CA 91343 USA. Univ Calif Los Angeles, Biobehav Sci & Brain Res Inst, Sch Med, North Hills, CA 91343 USA. Vet Adm Greater Los Angeles Hlth Syst Sepulveda, Sepulveda, CA USA. Russian Acad Sci, Inst Evolut Physiol & Biochem, St Petersburg 194223, Russia. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat, Sch Med, Neurobiol Res 151A3,VA GLAHS,16111 Plummer St, North Hills, CA 91343 USA. FU NHLBI NIH HHS [HL 60296, HL 41370, P50 HL060296, R01 HL041370, R37 HL041370] NR 82 TC 14 Z9 14 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 15 PY 2002 VL 545 IS 3 BP 997 EP 1006 DI 10.1113/jphysiol.2002.028985 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 631QK UT WOS:000180178300022 PM 12482902 ER PT J AU Koh, EY Chen, T Daley, GQ AF Koh, EY Chen, T Daley, GQ TI Novel retroviral vectors to facilitate expression screens in mammalian cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TUMOR SUPPRESSIVE FUNCTIONS; DEATH-ASSOCIATED PROTEINS; V(D)J RECOMBINATION; GENE IDENTIFICATION; ANTISENSE RNA; HELPER-FREE; HIGH-TITER; CLONING; CDNA; SEQUENCES AB As tools for functional genomics, expression profiling and proteomics provide correlative data, while expression cloning screens can link genes directly to biological function. However, technical limitations of gene transfer, expression, and recovery of candidate genes have limited wider application of genome-wide expression screens. Here we describe the pEYK retroviral vectors, which maintain high titers and robust gene expression while addressing the major bottleneck of expression cloning- efficient candidate gene recovery. By exploiting schemes for enhanced PCR rescue or strategies for direct isolation of proviral DNA as plasmids in bacterial hosts, the pEYK vectors facilitate cDNA isolation from selected cells and enable rapid iteration of screens and genetic reversion analyses to validate gene candidates. These vectors have proven useful to identify genes linked to cell proliferation, senescence and apoptosis. C1 Whitehead Inst, Cambridge, MA 02142 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [T32 CA009541, CA86991, CA09541, CA76418, R01 CA086991]; NIGMS NIH HHS [GM07753-22, T32 GM007753] NR 42 TC 25 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 15 PY 2002 VL 30 IS 24 AR e142 DI 10.1093/nar/gnf142 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636PT UT WOS:000180465600007 PM 12490733 ER PT J AU Gleit, ZL Fuchimoto, Y Yamada, K Melendy, E Scheier-Dolberg, R Monajati, L Coburn, RC Neville, DM Sachs, DH Huang, CA AF Gleit, ZL Fuchimoto, Y Yamada, K Melendy, E Scheier-Dolberg, R Monajati, L Coburn, RC Neville, DM Sachs, DH Huang, CA TI Variable relationship between chimerism and tolerance after hematopoietic cell transplantation without myelosuppressive conditioning SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; WHOLE-BODY IRRADIATION; LARGE-ANIMAL-MODEL; MIXED CHIMERISM; ALLOGRAFT TOLERANCE; MINIATURE SWINE; MONOCLONAL-ANTIBODIES; PREPARATIVE REGIMEN; T-CELLS; INDUCTION AB Background. We have previously described a mixed chimerism protocol that avoids myelosuppressive conditioning and permits hematopoietic cell transplantation across MHC barriers without the need for whole body irradiation in miniature swine. Here, we report our current experience including animals conditioned without thymic irradiation, and we, attempt to define the relationship between long-term chimerism and stable tolerance in these animals. Methods. Recipient swine received in vivo T-cell depletion, with or without thymic irradiation on day -2. Cyclosporine was administered for 30 to 60 days beginning on day -1. A total of 1 to 2 x 10(10)/kg cytokine-mobilized donor hematopoietic cells were infused during 3 days. Chimerism was determined by flow cytometry. In vitro tolerance assays and donor-matched kidney transplantation were performed after cessation of cyclosporine. Results. Most recipients maintained stable chimerism (26 of 35) and were specifically tolerant to donor-matched cells in vitro regardless of whether they received thymic irradiation. Donor-matched kidney transplantations performed in chimeric animals without in vitro antidonor immune responses were accepted without immunosuppression. Some animals developed in vitro evidence of antidonor MHC responsiveness despite the persistence of donor cells in the peripheral blood. Donor-matched kidney transplantations performed in the face of these responses were rejected. Conclusions. These data indicate that this nonmyelosuppressive protocol can induce stable chimerism. and robust tolerance even in animals conditioned without thymic irradiation. However, the data also demonstrate that macrochimerism does not always correlate with tolerance. Lack of in vitro antidonor immune responses in chimeric animals is an important predictor of renal allograft acceptance in this model. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Huang, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [1R01 CA79989-01A1]; NHLBI NIH HHS [1R01 HL63430-01]; NIAID NIH HHS [1F32AI-10306] NR 24 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2002 VL 74 IS 11 BP 1535 EP 1544 DI 10.1097/01.TP.0000041571.28969.FA PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 627FB UT WOS:000179921700010 PM 12490786 ER PT J AU Yamaguchi, T Yamauchi, M Sugimoto, T Chauhan, D Anderson, KC Brown, EM Chihara, K AF Yamaguchi, T Yamauchi, M Sugimoto, T Chauhan, D Anderson, KC Brown, EM Chihara, K TI The extracellular calcium (Ca-o(2+))-sensing receptor is expressed in myeloma cells and modulates cell proliferation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE calcium-sensing receptor; multiple myeloma; U266 cells; IM-9 cells; RPMI8226 cells; proliferation ID ACTIVATED PROTEIN-KINASE; HUMAN MULTIPLE-MYELOMA; MARROW STROMAL CELLS; SENSING RECEPTOR; INTERLEUKIN-6 SECRETION; CA2+-SENSING RECEPTOR; FUNCTIONAL EXPRESSION; POTENTIAL MEDIATOR; PLASMA-CELLS; BONE-DISEASE AB The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca-0(2+)) homeostasis by enabling parathyroid, kidney, and other cells to directly "sense" changes in Ca-0(2+). In multiple myeloma-associated bone disease, myeloma cells could raise the level of Ca-0(2+) within their immediate vicinity in the bone marrow microenvironment, through their known capacity to cause bone destruction by stimulating osteoclastic bone resorption. Thus if myeloma cells expressed the CaR, they might sense these locally elevated levels of Ca-0(2+), which could, in turn, potentially modify their function(s) in ways that could contribute to myeloma bone disease or other aspects of the pathophysiology of this disabling hematological malignancy. In this study, we examined the expression of the CaR in three myeloma cell lines, human U266, IM-9, and RPMI8226 cells. CaR protein was present in all three cell lines as assessed by immunocytochemistry and Western blot analysis using a monoclonal antibody specific for the CaR. Moreover, the use of reverse transcription-polymerase chain reaction (RT-PCR) with CaR-specific primers, followed by nucleotide sequencing of the amplified products, also identified CaR transcripts in the three cell lines. Exposure to known polycationic agonists of the CaR, including high Ca-0(2+) (2.5 mM), neomycin, and gadolinium (Gd3+) as well as a specific CaR activator, NPS 8467, augmented cell proliferation in all three cell lines. RT-PCR revealed that U266 cells, but not IM-9 cells or RPMI8226 cells, expressed interleukin-6 (IL-6), the expression of which was not enhanced by treatments with CaR agonists. Therefore, taken together, our data first document the fact that the myeloma cell lines, U266, IM-9, and RPMI8226, all express CaR protein and mRNA. Moreover, the CaR expressed on myeloma cells could sense the locally high levels of Ca-0(2+) in the vicinity of sites of osteoclastic bone resorption and stimulate their proliferation in an IL-6-independent manner. These processes may result in promoting further growth of the tumor and aggravating the associated bone disease. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Takatsuki Gen Hosp, Dept Internal Med, Takatsuki, Osaka 5691192, Japan. Kobe Univ, Sch Med, Dept Clin Mol Med, Div Endocrinol Metab Neurol & Hematol Oncol, Kobe, Hyogo 650, Japan. Dana Farber Canc Inst, Dept Med, Div Hematol Malignancies, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Endocrine Hypertens Div, Boston, MA 02115 USA. RP Yamaguchi, T (reprint author), Takatsuki Gen Hosp, Dept Internal Med, 1-3-13 Kosobe Cho, Takatsuki, Osaka 5691192, Japan. NR 43 TC 29 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 13 PY 2002 VL 299 IS 4 BP 532 EP 538 AR PII S0006-291X(02)02690-6 DI 10.1016/S0006-291X(02)02690-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 625LN UT WOS:000179818100003 PM 12459170 ER PT J AU Liu, DX Scafidi, J Prada, AE Zahedi, K Davis, AE AF Liu, DX Scafidi, J Prada, AE Zahedi, K Davis, AE TI Nuclear phosphatases and the proteasome in suppression of STAT1 activity in hepatocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE C1 inhibitor; interferon-gamma; signal transducer and activator of transcription-1; phosphatases; mitogen-activated protein kinase phosphatase; proteasome; ubiquitin ID PROTEIN-TYROSINE-PHOSPHATASE; STIMULATED JAK/STAT PATHWAY; HUMAN-SKIN FIBROBLASTS; GAMMA-INTERFERON; GENE-EXPRESSION; C1 INHIBITOR; KINASE PHOSPHATASE-1; TRANSCRIPTION FACTOR; IN-VIVO; UBIQUITIN AB IFN-gamma induction of C1 inhibitor (C1INH) is mediated by an IFN-gamma-activated sequence (GAS), via binding of signal transducer and activator of transcription 1 (STAT1). These studies focused on the factors responsible for down-regulation of nuclear STAT1 in hepatocytes, the primary site of synthesis of C1INH. The activity of nuclear STAT1 following stimulation with IFN-gamma was sustained with the phosphatase inhibitor, pervanadate, or the proteasome inhibitor, lactacystin. Pervanadate prolonged STAT1 activation and blocked the inactivation of nuclear STAT1. Binding of ubiquitin to phosphorylated STAT1 was detectable in cells treated with lactacystin. Staurosporine only moderately decreased the prolongation of nuclear phosphorylated STAT1 after pretreatment with pervanadate or lactacystin. An antisense mitogen-activated protein kinase phosphatase (MKP-1) oligonucleotide prolonged the accumulation of phosphorylated STAT1. These data are consistent with the hypothesis that down-regulation of IFN-gamma-mediated nuclear STAT1 binding in hepatocytes involves both dephosphorylation by MKP-1 and degradation via proteolysis by the ubiquitin-dependent proteasome pathway. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Cincinnati, Childrens Hosp Res Fdn, Div Nephrol, Cincinnati, OH 45229 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [HD333727, HD22082] NR 47 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 13 PY 2002 VL 299 IS 4 BP 574 EP 580 AR PII S0006-291X(02)02694-3 DI 10.1016/S0006-291X(02)02694-3 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 625LN UT WOS:000179818100010 PM 12459177 ER PT J AU Casper, AM Nghiem, P Arlt, MF Glover, TW AF Casper, AM Nghiem, P Arlt, MF Glover, TW TI ATR regulates fragile site stability SO CELL LA English DT Article ID DNA-REPLICATION; ATAXIA-TELANGIECTASIA; FHIT GENE; MOLECULAR CHARACTERIZATION; FREQUENT DELETIONS; INTEGRATION SITE; CANCER-CELLS; CHECKPOINT; FRA3B; EXPRESSION AB Conditions that partially inhibit DNA replication induce expression of common fragile sites. These sites form gaps and breaks on metaphase chromosomes and are deleted and rearranged in many tumors. Yet, the mechanism of fragile site expression has been elusive. We demonstrate that the replication checkpoint kinase ATR, but not ATM, is critical for maintenance of fragile site stability. ATR deficiency results in fragile site expression with and without addition of replication inhibitors. Thus, we propose that fragile sites are unreplicated chromosomal regions resulting from stalled forks that escape the ATR replication checkpoint. These findings have important implications for understanding both the mechanism of fragile site instability and the consequences of stalled replication in mammalian cells. C1 Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Cutaneous Oncol Unit, Boston, MA 02115 USA. RP Glover, TW (reprint author), Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RI Nghiem, Paul/A-9210-2011; OI Nghiem, Paul/0000-0003-2784-963X; Casper, Anne/0000-0003-4975-5749 FU NCI NIH HHS [CA43222]; NIAMS NIH HHS [K08-AR02087]; NIGMS NIH HHS [GM38627] NR 62 TC 389 Z9 396 U1 5 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 13 PY 2002 VL 111 IS 6 BP 779 EP 789 DI 10.1016/S0092-8674(02)01113-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 626GC UT WOS:000179862600005 PM 12526805 ER PT J AU Lin, YS Khokhlatchev, A Figeys, D Avruch, J AF Lin, YS Khokhlatchev, A Figeys, D Avruch, J TI Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 58,000-DALTON CELLULAR INHIBITOR; GENE DUPLICATION; CASPASE CLEAVAGE; KINASE PKR; ACTIVATION; P58(IPK); P53; IDENTIFICATION; CLONING; PHOSPHORYLATION AB The protein kinase MST1 is proapoptotic when overexpressed in an active form, however, its physiologic regulation and cellular targets are unknown. An overexpressed inactive MST1 mutant associates in COS-7 cells with an endogenous 761-amino acid polypeptide known as "death-associated protein 4" (DAP4). The DAPs are a functionally heterogeneous array of polypeptides previously isolated by Kimchi and colleagues (Kimchi, A. (1998) Biochim Biophys. Acta 1377, F13-F33 in a screen for elements involved in the interferon gamma-induced apoptosis of HeLa cells. DAP4, which is encoded by a member of a vertebrate-only gene family, contains no identifiable domains, but is identical over its amino-terminal 488 amino acids to p52(rIPK), a putative modulator of protein kinase R. DAP4 is a widely expressed, constitutively nuclear polypeptide that homodimerizes through its amino terminus and binds MST1 through its carboxyl-terminal segment. MST1 is predominantly cytoplasmic, but cycles continuously through the nucleus, as evidenced by its rapid accumulation in the nucleus after addition of the Crm1 inhibitor, leptomycin B. Overexpression of DAP4 does not cause apoptosis, however, coexpression of DAP4 with a submaximal amount of MST1 enhances MST1-induced apoptosis in a dose-dependent fashion. DAP4 is not significantly phosphorylated by MST1 nor does it alter MST1 kinase activity in vivo or in vitro. MST1-induced apoptosis is suppressed by a dominant interfering mutant of p53. MST1 is unable to directly phosphorylate p53, however, DAP4 binds endogenous and recombinant p53. DAP4 may promote MST1-induced apoptosis by enabling colocalization of MST with p53. C1 Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. MDS Proteom, Toronto, ON M9W 7H4, Canada. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, 50 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [T32 DK07028] NR 47 TC 59 Z9 63 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 47991 EP 48001 DI 10.1074/jbc.M202630200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600005 PM 12384512 ER PT J AU Zhang, BX Ma, XY Yeh, CK Lifschitz, MD Zhu, MX Katz, MS AF Zhang, BX Ma, XY Yeh, CK Lifschitz, MD Zhu, MX Katz, MS TI Epidermal growth factor-induced depletion of the intracellular Ca2+ store fails to activate capacitative Ca2+ ntry in a human salivary cell line SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; MEDIATED CALCIUM-ENTRY; CURRENT I-CRAC; PHOSPHOLIPASE-C; INOSITOL TRISPHOSPHATE; HUMAN-PLATELETS; PROTEIN-KINASE; RECEPTOR; INFLUX; CHANNELS AB Epidermal growth factor (EGF) is a multifunctional factor known to influence proliferation and function of a variety of cells. The actions of EGF are mediated by EGF receptor tyrosine kinase pathways, including stimulation of phospholipase Cgamma and mobilization of intracellular Ca2+ ([Ca2+](i)). Generally, agonist-mediated Ca2+ mobilization involves both Ca2+ release from internal stores and Ca2+ influx activated by store depletion (i.e. capacitative or store-operated Ca2+ influx). However, the role of capacitative Ca2+ entry in EGF-mediated Ca2+ mobilization is still largely unknown. In this study, we compared [Ca2+], signals elicited by EGF with those induced by agents (the muscarinic receptor agonist carbachol and thapsigargin (Tg)) known to activate capacitative Ca2+ entry. Unlike carbachol and Tg, EGF (5 nM) elicited a transient [Ca2+](i) signal without a plateau phase in the presence of extracellular Ca2+ and also failed to accelerate Mn2+ entry. Repletion of extracellular Ca2+ to cells stimulated with EGF in the absence of Ca2+ elicited an increase in [Ca2+](i), indicating that EGF indeed stimulates Ca2+ influx. However, the influx was activated at lower EGF concentrations than those required to stimulate Ca2+ release. Interestingly, the phospholipase C inhibitor U73122 completely inhibited Ca2+ release induced by both EGF and carbachol and also reduced Ca2+ influx responsive to carbachol but had no effect on Ca2+ influx induced by EGF. EGF-induced Ca2+ influx was potentiated by low concentrations (<5 ng/ml) of oligomycm, a mitochondrial inhibitor that blocks capacitative Ca2+ influx in other systems. Transient expression of the hTRPC3 protein enhanced Ca2+ influx responsive to carbachol but did not increase EGF-activated Ca2+ influx. Both EGF and carbachol depleted internal Ca2+ stores. Our results demonstrate that EGF-induced Ca2+ release from internal stores does not activate capacitative Ca2+ influx. Rather, EGF stimulates Ca2+ influx via a mechanism distinct from capacitative Ca2+ influx induced by carbachol and Tg. C1 Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Med Res Serv, Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. Ohio State Univ, Neurobiotechnol Ctr, Columbus, OH 43210 USA. RP Katz, MS (reprint author), 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. FU NIDCR NIH HHS [DE10756]; NINDS NIH HHS [NS42183] NR 42 TC 14 Z9 16 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 48165 EP 48171 DI 10.1074/jbc.M208077200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600027 PM 12368284 ER PT J AU Yoshida, K Miki, Y Kufe, D AF Yoshida, K Miki, Y Kufe, D TI Activation of SAPK/JNK signaling by protein kinase C delta in response to DNA damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYELOID-LEUKEMIA CELLS; LYN TYROSINE KINASE; TRANSDUCTION PATHWAY; IONIZING-RADIATION; PROTEOLYTIC ACTIVATION; INDUCED APOPTOSIS; GENE-EXPRESSION; FUNCTIONAL INTERACTION; CELLULAR-RESPONSE; JUN PROTOONCOGENE AB The cellular response to genotoxic stress includes activation of protein kinase Cdelta (PKCdelta). The functional role of PKCdelta in the DNA damage response is unknown. The present studies demonstrate that PKCdelta is required in part for induction of the stress-activated protein kinase (SAPK/JNK) in cells treated with 1-beta-D-arabinofuranosylcytosine (araC) and other genotoxic agents. DNA damage-induced SAPK activation was attenuated by W treatment with rottlerin, (ii) expression of a kinase-inactive PKCdelta(K-R) mutant, and (iii) down-regulation of PKCdelta by small interfering RNA (siRNA). Coexpression studies demonstrate that PKCdelta activates SAPK by an MKK7-dependent, SEK1-independent mechanism. Previous work has shown that the nuclear Lyn tyrosine kinase activates the MEKK1 --> MKK7 --> SAPK pathway but not through a direct interaction with MEKK1. The present results extend those observations by demonstrating that Lyn activates PKCdelta, and in turn, MEKK1 is activated by a PKCdelta-dependent mechanism. These findings indicate that PKCdelta functions in the activation of SAPK through a Lyn --> PKCdelta -> MEKK1 --> MKK7 --> SAPK signaling cascade in response to DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Genet, Tokyo 1138510, Japan. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA55241, CA29431] NR 46 TC 64 Z9 67 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 48372 EP 48378 DI 10.1074/jbc.M205485200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600054 PM 12377781 ER PT J AU Fukumoto, H Deng, A Irizarry, MC Fitzgerald, ML Rebeck, GW AF Fukumoto, H Deng, A Irizarry, MC Fitzgerald, ML Rebeck, GW TI Induction of the cholesterol transporter ABCA1 in central nervous system cells by liver X receptor agonists increases secreted A beta levels SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CEREBROSPINAL-FLUID; HIGH-DENSITY-LIPOPROTEIN; TANGIER-DISEASE PATIENTS; TRANSGENIC MOUSE MODEL; IN-SITU HYBRIDIZATION; E EPSILON-4 ALLELE; APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; CELLULAR CHOLESTEROL; HEAD-INJURY AB The expression, function, and regulation of the cholesterol efflux molecule, ABCA1, has been extensively examined in peripheral tissues but only poorly studied in the brain. Brain cholesterol metabolism is of interest because several lines of evidence suggest that elevated cholesterol increases the risk of Alzheimer's disease. We found a largely neuronal expression of ABCA1 in normal rat brain by in situ hybridization. ABCA1 message was dramatically up-regulated in neurons and glia in areas of damage by hippocampal AMPA lesion after 3-7 days. Immunoblot analysis demonstrated ABCA1 protein in cultured neuronal and glial cells, and expression was induced by ligands of the nuclear hormone receptors of the retinoid X receptor and liver X receptor family. ABCA1 was induced by treatment with retinoic acid and several oxysterols, including 22(R)-hydroxycholesterol and 24-hydroxycholesterol. Expression of an ABCA1-green fluorescent protein construct in neuroblastoma cells demonstrated fluorescence in perinuclear compartments and on the plasma membrane. Because the Abeta peptide is important in Alzheimer's disease pathogenesis, we examined whether ABCA1 induction altered Abeta levels. Treatment of neuroblastoma cells with retinoic acid and 22(R)-hydroxycholesterol caused significant increases in secreted Abeta40 (29%) and Abeta42 (65%). Treatment with a nonsteroidal liver X receptor ligand, TO-901317, similarly increased levels of secreted Abeta40 (25%) and Abeta42 (126%). The increase in secreted Abeta levels was reduced by RNAi blocking of ABCA1 expression. These data suggest that the cholesterol efflux molecule ABCA1 may also be involved in the secretion of the membrane-associated molecule, Abeta. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Rebeck, GW (reprint author), Alzheimer Res Unit, 114 16th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL10398, HL68988]; NIA NIH HHS [K08 AG00793, R01 AG14473] NR 60 TC 116 Z9 120 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 48508 EP 48513 DI 10.1074/jbc.M209085200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600072 PM 12384498 ER PT J AU Monks, NR Lerner, C Henriques, AT Farias, FM Schapoval, EES Suyenaga, ES da Rocha, AB Schwartsmann, G Mothes, B AF Monks, NR Lerner, C Henriques, AT Farias, FM Schapoval, EES Suyenaga, ES da Rocha, AB Schwartsmann, G Mothes, B TI Anticancer, antichemotactic and antimicrobial activities of marine sponges collected off the coast of Santa Catarina, southern Brazil SO JOURNAL OF EXPERIMENTAL MARINE BIOLOGY AND ECOLOGY LA English DT Article DE Polymastia janeirensis; Haliclona aff tubifera; Mycale arcuiris; Raspailia (syringella) sp. ID NEW-ZEALAND SPONGE; AKA ADOCIA SP; HALICLONA SP; MYCALAMIDE-A; MYCALE SP; ANTITUMOR AGENTS; CYTOTOXIC METABOLITES; DRUG DISCOVERY; ALKALOIDS; MACROLIDES AB This study reports the in vitro screening of 10 marine sponges (Porifera) collected from the coastline of Santa Catarina, southern Brazil, in the search for novel pharmaceuticals. Organic and aqueous extracts were tested for anticancer, antibacterial, antifungal and antichemotactic activities. Eight of the ten species tested demonstrated activity in one or more of the bioassays. Organic extracts of Polymastia janeirensis Boury-Esnauls, 1973, Haliclona aff tubifera George and Wilson, 1919, Mycale arcuiris Lemer and Hajdu, 2002 and Raspailia (syringella) sp. each demonstrated cytotoxicity at 100 mug/ml in an in vitro screening assay against the HT29 colorectal tumour cell line. Further analysis against three human tumour cell lines (HT29, U373 and NCI-H460) demonstrated IC50 concentrations ranging from 25 to 50 mug/ml. Aqueous extracts of six species P. janeirensis, M arcuiris, Raspailia (syringella) sp., Guitarra sp., Tedania ignis Duchassaing and Michelotti, 1864 and Pseudaxinella reticulata Ridley and Dendy, 1886 each significantly (p less than or equal to 0.05) retarded the migration of polymorphonuclear (PMN) leukocytes in a chemotactic assay. In antibacterial assays, only H. aff tubifera (four of five bacterial strains) and Axinella corrugata George and Wilson, 1919 (one of five bacterial strains) demonstrated activity. None of the 10 species demonstrated measurable antifungal activity. These extracts are currently undergoing further analysis to identify the active constituents. (C) 2002 Elsevier Science B.V. All rights reserved. C1 ULBRA, CINCAN, BR-92420280 Canoas, RS, Brazil. Museu Ciencias Nat, Fundacao Zoobot, BR-90690000 Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Fac Farm, BR-90610000 Porto Alegre, RS, Brazil. Hosp Clin Porto Alegre, SOAD, BR-90035003 Porto Alegre, RS, Brazil. RP Monks, NR (reprint author), Dana Farber Canc Inst, Smith Bldg Rm 936A,44 Binney St, Boston, MA 02115 USA. RI Monks, Noel/B-5886-2013; Schwartsmann, Gilberto/G-4256-2016 OI Monks, Noel/0000-0001-6587-9827; Schwartsmann, Gilberto/0000-0002-7850-1644 NR 53 TC 40 Z9 51 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-0981 J9 J EXP MAR BIOL ECOL JI J. Exp. Mar. Biol. Ecol. PD DEC 12 PY 2002 VL 281 IS 1-2 BP 1 EP 12 AR PII S0022-0981(02)00380-5 DI 10.1016/S0022-0981(02)00380-5 PG 12 WC Ecology; Marine & Freshwater Biology SC Environmental Sciences & Ecology; Marine & Freshwater Biology GA 635VW UT WOS:000180421300001 ER PT J AU Kwong, PD Doyle, ML Casper, DJ Cicala, C Leavitt, SA Majeed, S Steenbeke, TD Venturi, M Chaiken, I Fung, M Katinger, H Parren, PWLH Robinson, J Van Ryk, D Wang, LP Burton, DR Freire, E Wyatt, R Sodroski, J Hendrickson, WA Arthos, J AF Kwong, PD Doyle, ML Casper, DJ Cicala, C Leavitt, SA Majeed, S Steenbeke, TD Venturi, M Chaiken, I Fung, M Katinger, H Parren, PWLH Robinson, J Van Ryk, D Wang, LP Burton, DR Freire, E Wyatt, R Sodroski, J Hendrickson, WA Arthos, J TI HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; TYPE-1 GP120; EFFICIENT NEUTRALIZATION; CELLS; RETROVIRUS; EPITOPES; COMPLEX; FUSION AB The ability of human immunodeficiency virus (HIV-1) to persist and cause AIDS is dependent on its avoidance of antibody-mediated neutralization. The virus elicits abundant, envelope-directed antibodies that have little neutralization capacity(1). This lack of neutralization is paradoxical, given the functional conservation and exposure of receptor-binding sites on the gp120 envelope glycoprotein, which are larger than the typical antibody footprint(2) and should therefore be accessible for antibody binding. Because gp120-receptor interactions involve conformational reorganization(3), we measured the entropies of binding for 20 gp120-reactive antibodies. Here we show that recognition by receptor-binding-site antibodies induces conformational change. Correlation with neutralization potency and analysis of receptor-antibody thermodynamic cycles suggested a receptor-binding-site 'conformational masking' mechanism of neutralization escape. To understand how such an escape mechanism would be compatible with virus-receptor interactions, we tested a soluble dodecameric receptor molecule and found that it neutralized primary HIV-1 isolates with great potency, showing that simultaneous binding of viral envelope glycoproteins by multiple receptors creates sufficient avidity to compensate for such masking. Because this solution is available for cell-surface receptors but not for most antibodies, conformational masking enables HIV-1 to maintain receptor binding and simultaneously to resist neutralization. C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. GlaxosmithKline Pharmaceut, Dept Biol Struct, King Of Prussia, PA 19406 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Tanox Biosyst Inc, Cell Biol, Houston, TX 77025 USA. Univ Agr & Forestry, Inst Appl Microbiol, A-1190 Vienna, Austria. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Kwong, PD (reprint author), NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. OI Parren, Paul/0000-0002-4365-3859 NR 30 TC 562 Z9 584 U1 1 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 12 PY 2002 VL 420 IS 6916 BP 678 EP 682 DI 10.1038/nature01188 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 624GK UT WOS:000179751800048 PM 12478295 ER PT J AU Sambrano, GR Chandy, G Choi, S Decamp, D Hsueh, R Lin, KM Mock, D O'Rourke, N Roach, T Shu, HJ Sinkovits, B Verghese, M Bourne, H AF Sambrano, GR Chandy, G Choi, S Decamp, D Hsueh, R Lin, KM Mock, D O'Rourke, N Roach, T Shu, HJ Sinkovits, B Verghese, M Bourne, H TI Unravelling the signal-transduction network in B lymphocytes SO NATURE LA English DT Article ID LYMPHOMA-CELLS; WEHI-231; ACTIVATION; CHEMOKINES; EXPRESSION AB The Alliance for Cellular Signaling has chosen the mouse B lymphocyte as a model system to understand basic principles that govern cellular signalling. Progress to that end has focused initially on establishing a reproducible experimental cell system and characterizing essential signalling responses. Although unravelling this complex network will take years, findings revealed in the interim will prove immensely useful to the scientific community at large. C1 Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Univ Calif San Diego, San Diego Supercomp Ctr, La Jolla, CA 92093 USA. San Francisco Vet Adm Med Ctr, Dept Rheumatol, San Francisco, CA 94121 USA. RP Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM sambrano@cmp.ucsf.edu NR 22 TC 20 Z9 20 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 12 PY 2002 VL 420 IS 6916 BP 708 EP 710 DI 10.1038/nature01305 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 624GK UT WOS:000179751800055 PM 12478302 ER PT J AU Sambrano, GR Fraser, I Han, HP Ni, Y O'Connell, T Yan, Z Stull, JT AF Sambrano, GR Fraser, I Han, HP Ni, Y O'Connell, T Yan, Z Stull, JT TI Navigating the signalling network in mouse cardiac myocytes SO NATURE LA English DT Article ID SIGNALING PATHWAYS; CULTURE; HEART AB Cardiac myocytes have a complex network of signals that regulates their essential role in the rhythmic pumping of the heart. This network is an appealing model system in which to study the basic principles underlying cellular signalling mechanisms. Progress in this effort has come through the establishment of standardized myocyte isolation and culture procedures and characterization of important signalling responses. C1 Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. San Francisco Vet Adm Med Ctr, Dept Cardiol, San Francisco, CA 94121 USA. RP Sambrano, GR (reprint author), Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, 513 Parnassus Ave, San Francisco, CA 94143 USA. RI O'Connell, Timothy/D-5048-2013 NR 25 TC 67 Z9 67 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 12 PY 2002 VL 420 IS 6916 BP 712 EP 714 DI 10.1038/nature01306 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 624GK UT WOS:000179751800056 PM 12478303 ER PT J AU Unutzer, J Katon, W Callahan, CM Williams, JW Hunkeler, E Harpole, L Hoffing, M Della Penna, RD Noel, PH Lin, EHB Arean, PA Hegel, MT Tang, LQ Belin, TR Oishi, S Langston, C AF Unutzer, J Katon, W Callahan, CM Williams, JW Hunkeler, E Harpole, L Hoffing, M Della Penna, RD Noel, PH Lin, EHB Arean, PA Hegel, MT Tang, LQ Belin, TR Oishi, S Langston, C CA IMPACT Investigators TI Collaborative care management of late-life depression in the primary care setting - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MENTAL-HEALTH-SERVICES; EPIDEMIOLOGIC CATCHMENT-AREA; PATIENTS AGED 65; MAJOR DEPRESSION; OLDER ADULTS; QUALITY IMPROVEMENT; COST-EFFECTIVENESS; MINOR DEPRESSION; DISORDERS; SYMPTOMS AB Context Few depressed older adults receive effective treatment in primary care settings. Objective To determine the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) collaborative care management program for late-life depression. Design Randomized controlled trial with recruitment from July 1999 to August 2001. Setting Eighteen primary care clinics from 8 health care organizations in 5 states. Participants A total of 1801 patients aged 60 years or older with major depression (17%), dysthymic disorder (30%), or both (53%). Intervention Patients were randomly assigned to the IMPACT intervention (n=906) or to usual care (n=895). Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education, care management, and support of antidepressant management by the patient's primary care physician or a brief psychotherapy for depresssion, Problem Solving Treatment in Primary Care. Main Outcome Measures Assessments at baseline and at 3, 6, and 12 months for depression, depression treatments, satisfaction with care, functional impairment, and quality of life. Results At 12 months, 45% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline compared with 19% of usual care participants (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.71-4.38; P<.001). Intervention patients also experienced greater rates of depression treatment (OR, 2.98; 95% CI, 2.34-3.79; P<.001), more satisfaction with depression care (OR, 3.38; 95% CI, 2.66-4.30; P<.001), lower depression severity (range, 0-4; between-group difference, -0.4; 95% CI, -0.46 to -0.33; P<.001), less functional impairment (range, 0-10; between-group difference, -0.91; 95% CI, -1.19 to -0.64; P<.001), and greater quality of life (range, 0-10; between-group difference, 0.56; 95% CI, 0.32-0.79; P<.001) than participants assigned to the usual care group. Conclusion The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practices. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Ctr Hlth Serv Res, Los Angeles, CA 90024 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Indiana Univ, Ctr Aging Res, Regenstrief Inst Hlth Care, Indianapolis, IN 46204 USA. Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. Desert Med Grp, Palm Springs, CA USA. Kaiser Permanente So Calif, San Diego, CA USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Dartmouth Coll Sch Med, Dept Psychiat, Hanover, NH USA. John A Hartford Fdn, New York, NY USA. RP Unutzer, J (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Ctr Hlth Serv Res, 10920 Wilshire Blvd,Suite 300, Los Angeles, CA 90024 USA. RI Williams, Jr., John/A-3696-2008; OI Williams, Jr., John/0000-0002-5267-5558; Penna, Maria Pietronilla/0000-0002-0982-3893 NR 81 TC 1202 Z9 1210 U1 8 U2 74 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 DEC 11 PY 2002 VL 288 IS 22 BP 2836 EP 2845 DI 10.1001/jama.288.22.2836 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 623YM UT WOS:000179732600028 PM 12472325 ER PT J AU Lloyd-Jones, DM Larson, MG Leip, EP Beiser, A D'Agostino, RB Kannel, WB Murabito, JM Vasan, RS Benjamin, EJ Levy, D AF Lloyd-Jones, DM Larson, MG Leip, EP Beiser, A D'Agostino, RB Kannel, WB Murabito, JM Vasan, RS Benjamin, EJ Levy, D TI Lifetime risk for developing congestive heart failure - The Framingham Heart Study SO CIRCULATION LA English DT Article DE heart failure; risk factors; hypertension; myocardial infarction ID DISEASE; HYPERTENSION; PROGRESSION; PREVENTION; COMMUNITY AB Background-Congestive heart failure (CHF) is an increasing public health problem. Methods and Results-Among Framingham Heart Study subjects who were free of CHF at baseline, we determined the lifetime risk for developing overt CHF at selected index ages. We followed 3757 men and 4472 women from 1971 to 1996 for 124 262 person-years; 583. subjects developed CHF and 2002 died without prior CHF. At age 40 years, the lifetime risk for CHF was 21.0% (95% CI 18.7% to 23.2%) for men and 20.3% (95% CI 18.2% to 22.5%) for women. Remaining lifetime risk did not change with advancing index age because of rapidly increasing CHF incidence rates. At age 80 years, the lifetime risk was 20.2% (95% CI 16.1% to 24.2%) for men and 19.3% (95% CI 16.5% to 22.2%) for women. Lifetime risk for CHF doubled for subjects with blood pressure greater than or equal to160/100 versus <140/90 mm Hg. In a secondary analysis, we only considered those who developed CHF without an antecedent myocardial infarction; at age 40 years, the lifetime risk for CHF was 11.4% (95% CI 9.6% to 13.2%) for men and 15.4% (95% CI 13.5% to 17.3%) for women. Conclusions-When established clinical criteria are used to define overt CHF, the lifetime risk for CHF is 1 in 5 for both men and women. For CHF occurring in the absence of myocardial infarction, the lifetime risk is 1 in 9 for men and 1 in 6 for women, which highlights the risk of CHF that is largely attributable to hypertension. These results should assist in predicting the population burden of CHF and placing greater emphasis on prevention of CHF through hypertension control and prevention of myocardial infarction. C1 NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. RP Lloyd-Jones, DM (reprint author), NHLBI, Framingham Heart Study, NIH, 73 Mt Wayte Ave, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K23 HL04253, N01-HC-25195] NR 19 TC 661 Z9 693 U1 1 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 10 PY 2002 VL 106 IS 24 BP 3068 EP 3072 DI 10.1161/01.CIR.00000.39105.49749.6F PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 624WQ UT WOS:000179785000027 PM 12473553 ER PT J AU Kuehne, FC Bethe, U Freedberg, K Goldie, SJ AF Kuehne, FC Bethe, U Freedberg, K Goldie, SJ TI Treatment for hepatitis C virus in human immunodeficiency virus-infected patients - Clinical benefits and cost-effectiveness SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Medical-Decision-Making CY SEP 25-26, 2000 CL CINCINNATI, OH SP Soc Med Decis Making ID QUALITY-OF-LIFE; ACTIVE ANTIRETROVIRAL THERAPY; CHRONIC LIVER-DISEASE; NON-B-HEPATITIS; TERM FOLLOW-UP; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; DOUBLE-BLIND TRIAL; NATURAL-HISTORY; HIV-INFECTION; NON-A AB Background: Hepatitis C virus (HCV) is an important cause of liver disease in human immunodeficiency virus (HIV)-infected patients. Objective: To assess the cost-effectiveness of alternative management strategies for chronic HCV in coinfected patients with moderate hepatitis. Methods: A state-transition model was used to simulate a cohort of HIV-infected patients with a mean CD4 cell count of 350 cells/muL and moderate chronic hepatitis C stratified by genotype. Strategies included interferon alfa (48 weeks), pegylated interferon alfa (48 weeks), interferon alfa and ribavirin (24 and 48 weeks), pegylated interferon alfa and ribavirin (48 weeks), and no treatment. Outcomes included life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Results: Treatment for moderate chronic HCV with combination therapy using an interferon-based regimen reduced the incidence of cirrhosis and provided gains in quality-adjusted life expectancy ranging from 6.2 to 13.9 months, depending on genotype. Regardless of genotype, the cost-effectiveness of interferon alfa and ribavirin for patients with moderate hepatitis was lower than $50 000 per QALY vs the next best strategy. With genotype 1, pegylated interferon alfa (vs interferon alfa) and ribavirin therapy provided an additional 1.6 quality-adjusted life-months for $40 000 per QALY. Because treatment is more effective with non-1 genotypes, pegylated interferon (vs interferon alfa) and ribavirin provided only 3 additional quality-adjusted life-months for $105 300 per QALY. For patients who were intolerant of ribavirin, monotherapy with pegylated interferon was always the most cost-effective option. Conclusions: Combination therapy for moderate hepatitis in coinfected patients will increase quality-adjusted life expectancy and have a cost-effectiveness ratio comparable to that of other well-accepted clinical interventions. C1 Harvard Univ, Program Econ Evaluat Med Technol, Sch Publ Hlth, Ctr Risk Anal,Dept Hlth Policy & Management, Boston, MA 02115 USA. Univ Cologne, Dept Internal Med, Cologne, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. RP Goldie, SJ (reprint author), Harvard Univ, Program Econ Evaluat Med Technol, Sch Publ Hlth, Ctr Risk Anal,Dept Hlth Policy & Management, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA. EM sgoldie@hsph.harvard.edu FU NIAID NIH HHS [R01 AI042006] NR 189 TC 32 Z9 35 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 9 PY 2002 VL 162 IS 22 BP 2545 EP 2556 DI 10.1001/archinte.162.22.2545 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 625EY UT WOS:000179805000005 PM 12456226 ER PT J AU Kurth, T Gaziano, JM Berger, K Kase, CS Rexrode, KM Cook, NR Buring, JE Manson, JE AF Kurth, T Gaziano, JM Berger, K Kase, CS Rexrode, KM Cook, NR Buring, JE Manson, JE TI Body mass index and the risk of stroke in men SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Academy-of-Neurology CY MAY 05-12, 2001 CL PHILADELPHIA, PENNSYLVANIA SP Amer Acad Neurol ID C-REACTIVE PROTEIN; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; FAT DISTRIBUTION; ADIPOSE-TISSUE; INTEROBSERVER AGREEMENT; SUBARACHNOID HEMORRHAGE; INSULIN-RESISTANCE; PHYSICIANS HEALTH; ISCHEMIC STROKE AB Background: Although obesity is an established risk factor for coronary heart disease, its role as a risk factor for stroke remains controversial. Methods: Prospective cohort study among 21414 US male physicians participating in the Physicians' Health Study. Incidence of total, ischemic, and hemorrhagic stroke was measured by self-report and confirmed by medical record review. We used Cox proportional hazards models to evaluate the association of body mass index (BMI), calculated as self-reported weight in kilograms divided by the square of the height in meters, with risk of total, ischemic, and hemorrhagic stroke. Results: During 12.5 years of follow-up, 747 strokes (631 ischemic, 104 hemorrhagic, and 12 undefined) occurred. Compared with participants with BMIs less than 23, those with BMIs of 30 or greater had an adjusted relative risk of 2.00 (95% confidence interval [CI], 1.48-2.71) for total stroke, 1.95 (95% CI, 1.39-2.72) for ischemic stroke, and 2.25 (95% CI 1.01-5.01) for hemorrhagic stroke. When BMI was evaluated as a continuous variable, each unit increase of BMI was associated with a significant 6% increase in the adjusted relative risks of total (95% CI 4%-8%), ischemic (95% CI 3%-8%), and hemorrhagic stroke (95% CI 1%-12%). Additional adjustment for hypertension, diabetes mellitus, and hypercholesterolemia slightly attenuated the risks for total and ischemic (relative risk, 4%; 95% CI 2%-7%), but not hemorrhagic, stroke. Conclusions: These prospective data indicate a significant increase in the relative risk of total stroke and its 2 major subtypes with each unit increase of BMI that is independent of the effects of hypertension, diabetes, and cholesterol. Because BMI is a modifiable risk factor, the prevention of stroke may be another benefit associated with preventing obesity in adults. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Univ Munster, Inst Epidemiol & Social Med, D-4400 Munster, Germany. RP Kurth, T (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. RI Kurth, Tobias/A-9243-2012; OI Kurth, Tobias/0000-0001-7169-2620; Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA 34944, CA 40360]; NHLBI NIH HHS [HL 34595, HL26490] NR 60 TC 220 Z9 229 U1 1 U2 7 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 DEC 9 PY 2002 VL 162 IS 22 BP 2557 EP 2562 DI 10.1001/archinte.162.22.2557 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 625EY UT WOS:000179805000006 PM 12456227 ER PT J AU Van Etten, RA AF Van Etten, RA TI Studying the pathogenesis of BCR-ABL(+) leukemia in mice SO ONCOGENE LA English DT Article DE CML; tyrosine kinase; retrovirus; Philadelphia chromosome ID CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL ONCOGENE; CHRONIC MYELOID-LEUKEMIA; COLONY-STIMULATING FACTOR; HEMATOPOIETIC-CELL LINES; GROWTH-FACTOR INDEPENDENCE; SERINE THREONINE KINASE; DNA-BINDING ACTIVITY; TYROSINE KINASE; C-ABL AB Animal models of BCR-ABL(+) leukemias have provided important new knowledge about the molecular pathophysiology of these diseases, and answered questions that are difficult or impossible to address using BCR-ABL-expressing cell lines or primary Ph+ leukemia samples from patients. The power of mouse models lies in their ability to recapitulate precisely the phenotypes of BCR-ABL(+) leukemias in vivo, but this comes at the price of significant complexity. Here I review recent studies of leukemias induced in mice by BCR-ABL with an emphasis on the intricate nature of these diseases and the need for careful pathological and molecular analysis. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NCI NIH HHS [CA90576] NR 74 TC 35 Z9 36 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 9 PY 2002 VL 21 IS 56 BP 8643 EP 8651 DI 10.1038/sj.onc.1206091 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 623ZF UT WOS:000179734300013 PM 12476310 ER PT J AU Tsuang, MT Stone, WS Tarbox, SI Faraone, SV AF Tsuang, MT Stone, WS Tarbox, SI Faraone, SV TI Treatment of nonpsychotic relatives of patients with schizophrenia: Six case studies SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT Schizophrenia: From Prediction to Prevention-The Challenge of the 21st Century CY NOV 30-DEC 01, 2000 CL LYON, FRANCE ID RISK; SCHIZOTAXIA; RISPERIDONE; INDICATORS; SIBLINGS; DEFICIT C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [5 U01 MH4631802, 1 R01MH4187901, 1R37MH4351801] NR 37 TC 10 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 8 PY 2002 VL 114 IS 8 BP 943 EP 948 DI 10.1002/ajmg.10363 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 618EL UT WOS:000179405500011 PM 12457391 ER PT J AU Small, GW AF Small, GW TI Use of neuroimaging to detect early brain changes in people at genetic risk for Alzheimer's disease SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE neuroimaging; Alzheimer's disease; apolipoprotein E; positron emission tomography; functional magnetic resonance imaging; genetic risk ID CEREBRAL BLOOD-FLOW; APOLIPOPROTEIN-E; SENSORY STIMULATION; ALLELE; EPSILON-4; ACTIVATION; DEMENTIA; ABILITY AB The neuropathological and cognitive changes. preceding Alzheimer's disease appear to begin subtly decades before symptoms. of the disease make the clinical diagnosis obvious. Clinical trials have begun to focus on preventive treatments designed to slow age-related cognitive decline and delay the onset of Alzheimer's disease in people with only mild memory complaints. Because people with few cognitive deficits represent a heterogeneous population, prevention studies require large samples in order to detect active drug effects. To address such challenges, recent neuroimaging studies have focused on middle-aged and older adults with only mild memory complaints and evaluated results according to the major known genetic risk for Alzheimer's disease, the apolipoprotein E-4 (APOE-4) allele. In studies using positron emission tomography during mental rest and functional magnetic resonance imaging during memory task performance, brain patterns differ according to genetic risk and are useful in predicting future decline measures and following disease progression in clinical trials. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Ctr Aging, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Small, GW (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Inst Neuropsychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIA NIH HHS [AG10123, AG13308]; NIMH NIH HHS [MH52453] NR 31 TC 19 Z9 19 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD DEC 7 PY 2002 VL 54 IS 12 BP 1561 EP 1566 AR PII S0169-409X(02)00151-5 DI 10.1016/S0169-409X(02)00151-5 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 632AN UT WOS:000180200900004 PM 12453673 ER PT J AU Bortfeld, T van Herk, M Jiang, SB AF Bortfeld, T van Herk, M Jiang, SB TI When should systematic patient positioning errors in radiotherapy be corrected? SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PROSTATE-CANCER; VERIFICATION PROCEDURE AB One way to reduce patient set-up errors in radiotherapy is to measure the position during the first N treatment fractions, and to do an unconditional correction of the set-up position once at the (N + 1)th fraction. This strategy is known as the 'no action level' protocol. The question is when to do the correction, i.e. what is the optimum value of N? We determine N by minimizing the expectation value of the total quadratic set-up error taken over all fractions. A central assumption that we make is that there is no time trend in the patient set-up. The result is a simple formula for the value of N, which is proportional to the square root of the total number of fractions, and to the ratio of the execution (delivery) error and preparation error. We also provide a formula for cases where the measurement error is not negligible. For typical cases the optimum value is N = 4. Because the optimum is shallow, the exact choice of N is uncritical. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Netherlands Canc Inst, Antoni Van Leeuwenhoek Huis, Dept Radiotherapy, NL-1066 CX Amsterdam, Netherlands. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. RI van Herk, Marcel/P-6307-2015 OI van Herk, Marcel/0000-0001-6448-898X NR 9 TC 43 Z9 43 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 DEC 7 PY 2002 VL 47 IS 23 BP N297 EP N302 AR PII S0031-9155(02)53095-5 DI 10.1088/0031-9155/47/23/401 PG 6 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 633JM UT WOS:000180279500016 PM 12502052 ER PT J AU Benarafa, C Collins, ME Hamblin, AS Cunningham, FM AF Benarafa, C Collins, ME Hamblin, AS Cunningham, FM TI Role of the chemokine eotaxin in the pathogenesis of equine sweet itch SO VETERINARY RECORD LA English DT Article ID ATOPIC-DERMATITIS; EXPRESSION; EOSINOPHILS; DISEASE; HYPERSENSITIVITY; INTERLEUKIN-5; ANTAGONIST; PROTEIN-4; POTENT; SKIN AB The chemokine eotaxin is involved in the recruitment of eosinophils and T helper 2 lymphocytes in human allergic diseases, and drugs that block its activity, including eotaxin receptor (CCR3) antagonists, are being developed. The authors have recently cloned the horse ortholog of eotaxin and shown that it can induce equine eosinophil migration and activation in vitro. Moreover, eotaxin MRNA expression was upregulated in cultured horse dermal fibroblasts exposed to equine interieukin-4, suggesting a possible source of this eosinophil chemoattractant in equine skin. The results of this study show that eotaxin and monocyte chemoattractant protein (MCP) 1, but not MCP-2 or MCP-4, MRNA expression is upregulated in skin biopsies of sweet itch lesions when eosinophils are present, when compared with clinically normal skin from the same ponies. C1 Univ London Royal Vet Coll, Dept Pathol & Infect Dis, N Mymms AL9 7TA, Herts, England. Univ London Royal Vet Coll, Dept Vet Basic Sci, N Mymms AL9 7TA, Herts, England. RP Benarafa, C (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. OI Benarafa, Charaf/0000-0002-2049-7769 NR 22 TC 11 Z9 11 U1 1 U2 1 PU BRITISH VETERINARY ASSOC PI LONDON PA 7 MANSFIELD ST, LONDON W1M 0AT, ENGLAND SN 0042-4900 J9 VET REC JI Vet. Rec. PD DEC 7 PY 2002 VL 151 IS 23 BP 691 EP 693 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 626YV UT WOS:000179902100006 PM 12503787 ER PT J AU Dolgilevich, S Zaidi, N Song, JB Abe, E Moonga, BS Sun, L AF Dolgilevich, S Zaidi, N Song, JB Abe, E Moonga, BS Sun, L TI Transduction of TAT fusion proteins into osteoclasts and osteoblasts SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MAMMALIAN-CELLS; CALCINEURIN AB It has been difficult to transduce primary cultures of bone cells with proteins of interest. Here, we report the development and validation of a new technology for transduction of osteoblasts and osteoclasts with peptides and moderately sized proteins. Fusion proteins between TAT, an 11 amino acid Arg-rich sequence derived from the HIV protein, and either hemagglutinin or calcineurin Aalpha were synthesized and purified. Exposure of osteoblasts and osteoclasts in primary culture to either TAT-HA or TAT-calcineurin Aalpha resulted in a rapid (within 10 min) intracellular movement of the fusion protein evident on co-immunostaining. Almost 99% of cells were transduced and the fusion protein was retained in similar to50% of the cells for up to 5 days. TAT did not abolish the functionality of calcineurin Aalpha; the fusion protein stimulated osteoblast differentiation and inhibited osteoclastic resorption. We expect that our studies will provide a firm basis for the future development of TAT fusion proteins for critical molecules involved in bone cell differentiation and function. (C) 2002 Elsevier Science (USA). All rights reserved. C1 CUNY Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, GRECC, New York, NY 10029 USA. RP Sun, L (reprint author), CUNY Mt Sinai Sch Med, Mt Sinai Bone Program, 1 Gustave L Levy Pl,PO 1055, New York, NY 10029 USA. NR 12 TC 18 Z9 18 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 6 PY 2002 VL 299 IS 3 BP 505 EP 509 AR PII S0006-291X(02)02664-5 DI 10.1016/S0006-291X(02)02664-5 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 625LM UT WOS:000179818000028 PM 12445831 ER PT J AU Moore, KJ El Khoury, J Medeiros, LA Terada, K Geula, C Luster, AD Freeman, MW AF Moore, KJ El Khoury, J Medeiros, LA Terada, K Geula, C Luster, AD Freeman, MW TI A CD36-initiated signaling cascade mediates inflammatory effects of beta-amyloid SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MACROPHAGE SCAVENGER RECEPTORS; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE; PPAR-GAMMA; TNF-ALPHA; MICROGLIA; CD36; ATHEROSCLEROSIS; NEUROTOXICITY; PATHWAYS AB beta-Amyloid accumulation is associated with pathologic changes in the brain in Alzheimer's disease and has recently been identified in plaques of another chronic inflammatory disorder, atherosclerosis. The class B scavenger receptor, CD36, mediates binding of fibrillar beta-amyloid to cells of the monocyte/macrophage lineage, including brain macrophages (microglia). In this study, we demonstrate that in microglia and other tissue macrophages, beta-amyloid initiates a CD36-dependent signaling cascade involving the Src kinase family members, Lyn and Fyn, and the mitogen-activated protein kinase, p44/42. Interruption of this signaling cascade, through targeted disruption of Src kinases downstream of CD36, inhibits macrophage inflammatory responses to beta-amyloid, including reactive oxygen and chemokine production, and results in decreased recruitment of microglia to sites of amyloid deposition in vivo. The finding that engagement of CD36 by beta-amyloid initiates a Src kinase-dependent production of inflammatory mediators in cells of the macrophage lineage reveals a novel receptor-mediated pro-inflammatory signaling pathway of potential therapeutic importance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Aging, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, 55 Fruit St,GRJ 1328, Boston, MA 02114 USA. OI Moore, kathryn/0000-0003-2505-2547 FU NHLBI NIH HHS [R01 HL45098]; NIA NIH HHS [R01AG20255-01]; NIDDK NIH HHS [P01 DK50305]; NINDS NIH HHS [NS41330-02] NR 30 TC 203 Z9 208 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 6 PY 2002 VL 277 IS 49 BP 47373 EP 47379 DI 10.1074/jbc.M208788200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622TT UT WOS:000179663700070 PM 12239221 ER PT J AU Lepourcelet, M Shivdasani, RA AF Lepourcelet, M Shivdasani, RA TI Characterization of a novel mammalian groucho isoform and its role in transcriptional regulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSDUCIN-LIKE-ENHANCER; AMINO-TERMINAL ENHANCER; EPITHELIAL STEM-CELL; BETA-CATENIN; COLORECTAL-CANCER; MEDIATED TRANSCRIPTION; DROSOPHILA ENHANCER; SIGNALING ACTIVITY; XENOPUS EMBRYOS; BINDING-PROTEIN AB The Wnt/beta-catenin/Tcf pathway serves important functions in embryonic development and is constitutively activated in human colorectal cancer. The nuclear output of Wnt signaling is mediated by a complex between DNA-binding proteins of the TCF family and the transcriptional coactivator beta-catenin. Groucho proteins act to repress transcriptional activation by beta-cateninTcf complexes, probably by interacting directly with Tcf transcription factors. We have identified several splice forms of the mouse Groucho Grg1 gene expressed in the developing intestine. Prominent among these is a novel and abundant isoform, Grg1-S, which we characterize in this report. Grg1-S has highest homology with the TLE family of large Groucho proteins but features only the amino-terminal Q and glycine- and proline-rich domains typical of the Groucho/AES subfamily. Grg1-S is expressed in development and in several adult mouse tissues. Expression in the adult small intestine is highest at the base of the crypts of Lieberkuhn. Grg1-S acts to antagonize beta-catenin activity in Xenopus axis duplication and luciferase reporter assays in mammalian cells. Taken together, these findings suggest that Grg1-S may operate in conjunction with beta-catenin and Tcf factors to regulate vertebrate gut epithelial cell differentiation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 67 TC 17 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 6 PY 2002 VL 277 IS 49 BP 47732 EP 47740 DI 10.1074/jbc.M208154200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622TT UT WOS:000179663700116 PM 12359720 ER PT J AU LaPlante, JM Falardeau, J Sun, M Kanazirska, M Brown, EM Slaugenhaupt, SA Vassilev, PM AF LaPlante, JM Falardeau, J Sun, M Kanazirska, M Brown, EM Slaugenhaupt, SA Vassilev, PM TI Identification and characterization of the single channel function of human mucolipin-1 implicated a disorder affecting the in mucolipidosis type IV, lysosomal pathway SO FEBS LETTERS LA English DT Article DE mucolipin; mucolipidosis; lysosome; exocytosis; channel; late endosome ID POLYCYSTIC KIDNEY-DISEASE; ABNORMAL TRANSPORT; MEMBRANE-PROTEIN; GENE; CA2+; FUSION; ION; PURIFICATION; EXOCYTOSIS; MUTATIONS AB Mucolipin-1 (MLN1) is a membrane protein with homology to the transient receptor potential channels and other non-selective cation channels. It is encoded by the MCOLN1 gene, which is mutated in patients with mucolipidosis type IV (MLIV), an autosomal recessive disease that is characterized by severe abnormalities in neurological development as well as by ophthalmologic defects. At the cellular level, MLIV is associated with abnormal lysosomal sorting and trafficking. Here we identify the channel function of human MLN1 and characterize its properties. MLN1 represents a novel Ca2+-permeable channel that is transiently modulated by changes in [Ca2+]. It is also permeable to Na+ and K+. Large unitary conductances were measured in the presence of these cations. With its Ca2+ permeability and modulation by [Ca2+], MLN1 could play a major role in Ca2+ transport regulating lysosomal exocytosis and potentially other phenomena related to the trafficking of late endosomes and lysosomes. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Brigham & Womens Hosp, Dept Med, Diabet & Hypertens & Membrane Biol Program, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA 02115 USA. Ctr Prostate Dis Res, Rockville, MD 20852 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02115 USA. RP Vassilev, PM (reprint author), Brigham & Womens Hosp, Dept Med, Diabet & Hypertens & Membrane Biol Program, Div Endocrinol, 221 Longwood Ave, Boston, MA 02115 USA. FU NINDS NIH HHS [NS39995] NR 27 TC 95 Z9 98 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 4 PY 2002 VL 532 IS 1-2 BP 183 EP 187 AR PII S0014-5793(02)03670-0 DI 10.1016/S0014-5793(02)03670-0 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 625CK UT WOS:000179799200035 PM 12459486 ER PT J AU Kalayoglu, MV Libby, P Byrne, GI AF Kalayoglu, MV Libby, P Byrne, GI TI Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID CORONARY HEART-DISEASE; ABDOMINAL AORTIC-ANEURYSMS; BLOOD MONONUCLEAR-CELLS; HUMAN ENDOTHELIAL-CELLS; HUMAN ATHEROSCLEROTIC PLAQUES; SECONDARY PREVENTION TRIAL; LOW-DENSITY-LIPOPROTEIN; VASCULAR SMOOTH-MUSCLE; REACTIVE T-LYMPHOCYTES; ARTERY DISEASE AB Recent appreciation of atherosclerosis as a chronic, inflammatory disease has rekindled efforts to examine the role that infectious agents may play in atherogenesis. In particular, much interest has focused on infection with Chlamydia pneumoniae. The possibility that a prokaryote contributes to atherogenesis has high clinical interest, as C pneumoniae infection may be a treatable risk factor. To review the evidence implicating ( pneumoniae in the pathogenesis of atherosclerosis, we searched MEDLINE for articles published between January 1966 and October 2002 on the association of C pneumoniae and atherosclerosis. We also used online resources, texts, meeting abstracts, and expert opinion. We included 5 types of studies (epidemiological, pathology based, animal model, cell biology, and human antibiotic treatment trials) and extracted diagnostic, pathophysiologic, and therapeutic information from the selected literature; consensus was reached on interpretation discrepancies. Chlamydia pneumoniae is associated with atherosclerosis by epidemiological and pathology-based studies. Animal model and cell biology studies suggest that the pathogen can modulate atheroma biology, including lipid- and inflammatory-related processes. Although some preliminary antibiotic treatment trials in patients with coronary artery disease indicated a reduction in recurrent coronary events, larger studies have not shown benefits in individuals with stable coronary artery disease. It is unlikely that C pneumoniae infection is necessary to initiate atherosclerosis. Furthermore-conventional antibiotic therapy may not eradicate the organism or reduce mortality in individuals with atherosclerotic vascular disease. Nevertheless, the current body of evidence establishes this pathogen as a plausible, potentially modifiable risk factor in cardiovascular disease. C1 Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Byrne, GI (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, 858 Madison Ave,Suite 801, Memphis, TN 38163 USA. FU NHLBI NIH HHS [R01 HL071735]; NIAID NIH HHS [R01 AI019782] NR 127 TC 182 Z9 188 U1 0 U2 3 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 DEC 4 PY 2002 VL 288 IS 21 BP 2724 EP 2731 DI 10.1001/jama.288.21.2724 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 620UA UT WOS:000179549800032 PM 12460096 ER PT J AU Morrison, DA Sethi, G Sacks, J Henderson, WG Grover, F Sedlis, S Esposito, R AF Morrison, DA Sethi, G Sacks, J Henderson, WG Grover, F Sedlis, S Esposito, R CA Inv Dep Veterans Affairs Cooperat TI Percutaneous coronary intervention versus repeat bypass surgery for patients with medically refractory myocardial ischemia - AWESOME randomized trial and registry experience with post-CABG patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID GRAFT-SURGERY; RISK-FACTORS; MORTALITY; ANGIOPLASTY AB OBJECTIVES This report compares long-term percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) survival among post-CABG patients included in the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial and prospective registry. BACKGROUND Repeat CABG surgery is associated with a higher risk of mortality than first-time CABG. The AWESOME is the first randomized trial comparing CABG with PCI to include post-CABG patients. METHODS Over a five-year period (1995 to 2000), patients at 16 hospitals were screened to identify a cohort of 2,431 individuals who had medically refractory myocardial ischemia and at least one of five high-risk factors. There were 454 patients in the randomized trial, of whom 142 had prior CABG. In the physician-directed registry of 1,650 patients, 719 had prior CABG. Of the 327 patient-choice registry patients, 119 had at least one prior CABG. The CABG and PCI survivals for the three groups were compared using Kaplan-Meier curves and log-rank tests. RESULTS The CABG and PCI three-year survival rates were 73% and 76% respectively for the 142 randomized patients (75 and 67 patients) (log-rank = NS). In the physician-directed registry, 155 patients were assigned to reoperation and 357 to PCI (207 received medical therapy); 36-month survivals were 71% and 77% respectively (log-rank = NS). In the patient-choice registry, 32 patients chose reoperation and 74 chose PCI (13 received medical therapy); 36-month survivals were 65% and 86% respectively (log-rank test p = 0.01). CONCLUSION Percutaneous coronary intervention is preferable to CABG for many post-CABG patients. (C) 2002 by the American College of Cardiology Foundation. C1 Tucson VA Med Ctr, Tucson, AZ USA. Univ Arizona, Tucson, AZ 85724 USA. Hines VA Cooperat Studies, Hines, IL USA. Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Denver, CO 80202 USA. New York VA Med Ctr, New York, NY USA. NYU, New York, NY 10016 USA. RP Morrison, DA (reprint author), So Arizona Vet Affairs Healthcare Syst, 3601 S 6th St, Tucson, AZ 85723 USA. NR 14 TC 59 Z9 62 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 4 PY 2002 VL 40 IS 11 BP 1951 EP 1954 AR PII S0735-1097(02)02560-3 DI 10.1016/S0735-1097(02)02560-3 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 621WE UT WOS:000179613400008 PM 12475454 ER PT J AU Narod, SA Dube, MP Klijn, J Lubinski, J Lynch, HT Ghadirian, P Provencher, D Heimdal, K Moller, P Robson, M Offit, K Isaacs, C Weber, B Friedman, E Gershoni-Baruch, R Rennert, G Pasini, B Wagner, T Daly, M Garber, JE Neuhausen, SL Ainsworth, P Olsson, H Evans, G Osborne, M Couch, F Foulkes, WD Warner, E Kim-Sing, C Olopade, O Tung, N Saal, HM Weitzel, J Merajver, S Gauthier-Villars, M Jernstrom, H Sun, P Brunet, JS AF Narod, SA Dube, MP Klijn, J Lubinski, J Lynch, HT Ghadirian, P Provencher, D Heimdal, K Moller, P Robson, M Offit, K Isaacs, C Weber, B Friedman, E Gershoni-Baruch, R Rennert, G Pasini, B Wagner, T Daly, M Garber, JE Neuhausen, SL Ainsworth, P Olsson, H Evans, G Osborne, M Couch, F Foulkes, WD Warner, E Kim-Sing, C Olopade, O Tung, N Saal, HM Weitzel, J Merajver, S Gauthier-Villars, M Jernstrom, H Sun, P Brunet, JS TI Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OVARIAN-CANCER; WOMEN AB Background: Oral contraceptive use has been associated with an increase in the risk of breast cancer in young women. We examined whether this association is seen in women at high risk of breast cancer because they carry a mutation in one of two breast cancer susceptibility genes, BRCA1 and BRCA2. Methods: We performed a matched case-control study on 1311 pairs of women with known deleterious BRCA1 and/or BRCA2 mutations recruited from 52 centers in 11 countries. Women who had been diagnosed with breast cancer were matched to control subjects by year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of ovarian cancer. All study subjects completed a questionnaire about oral contraceptive use. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. All statistical tests were two-sided. Results: Among BRCA2 mutation carriers, ever use of oral contraceptives was not associated with an increased risk of breast cancer (OR = 0.94, 95% CI = 0.72 to 1.24). For BRCAI mutation carriers, ever use of oral contraceptives was associated With a modestly increased risk of breast cancer (OR = 1.20, 95 % CI = 1.02 to 1.40). However, compared with BRCA1 mutation carriers who never used oral contraceptives, those who used oral contraceptives for at least 5 years had an increased risk of breast cancer (OR = 1.33, 95% CI = 1.11 to 1.60), as did those who used oral contraceptives before age 30 (OR = 1.29, 95% CI = 1.09 to 1.52), those who were diagnosed with breast cancer before age 40 (OR = 1.38, 95% CI = 1.11 to 1.72), and those who first used oral contraceptives before 1975 (OR = 1.42, 95 % CI = 1.17 to 1.75). Conclusions: Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for 5 or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers are limited. C1 Algorithme Pharma, Montreal, PQ, Canada. Inst Curie, Sev Genet Oncol, Paris, France. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. City Hosp Hosp, Duarte, CA USA. Childrens Hosp, Med Ctr, Div Human Genet, Hereditary Canc Program, Cincinnati, OH 45229 USA. Beth Israel Deaconess Hosp, Boston, MA USA. Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60637 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Sunnybrook & Womens Coll, Hlth Sci Ctr, Toronto, ON, Canada. McGill Univ, Dept Oncol & Human Genet, Program Canc Genet, Montreal, PQ, Canada. Mayo Clin, Rochester, MN USA. Strang Canc Prevent Ctr, New York, NY USA. St Marys Hosp, Manchester M13 0JH, Lancs, England. Univ Lund Hosp, Dept Oncol, Jubileum Inst, S-22185 Lund, Sweden. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Univ Utah, Dept Med Informat, Salt Lake City, UT 84112 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria. Ist Nazl Tumori, I-20133 Milan, Italy. Carmel Hosp, Natl Canc Control Ctr, Haifa, Israel. Rambam Med Ctr, Inst Genet, Haifa, Israel. Chaim Sheba Med Ctr, Oncogenet Unit, IL-52621 Tel Hashomer, Israel. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. Mem Sloan Kettering Canc Ctr, Dept Human Genet & Med, New York, NY 10021 USA. Norwegian Radium Hosp, Dept Canc Genet, Oslo, Norway. Norwegian Radium Hosp, Dept Canc Genet, Oslo, Norway. Notre Dame Hosp, Dept Obstet & Gynecol, Montreal, PQ, Canada. Univ Montreal, Hotel Dieu, CHUM, Epidemiol Res Unit, Montreal, PQ, Canada. Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE USA. Pomeranian Med Univ, Szczecin, Poland. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Dr Daniel Den Hoed Canc Ctr, NL-3008 AE Rotterdam, Netherlands. Univ Toronto, Ctr Res Womens Hlth, Toronto, ON M5G 1N8, Canada. RP Narod, SA (reprint author), Univ Toronto, Ctr Res Womens Hlth, 790 Bay St,Rm 750, Toronto, ON M5G 1N8, Canada. RI Dube, Marie-Pierre/B-9364-2008; OI Dube, Marie-Pierre/0000-0001-8442-4393; Robson, Mark/0000-0002-3109-1692 FU NCI NIH HHS [CA 74415]; PHPPO CDC HHS [PHS R01 63678] NR 15 TC 200 Z9 203 U1 2 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 4 PY 2002 VL 94 IS 23 BP 1773 EP 1779 PG 7 WC Oncology SC Oncology GA 619ZF UT WOS:000179507300010 PM 12464649 ER PT J AU Nagy, JA Vasile, E Feng, D Sundberg, C Brown, LF Detmar, MJ Lawitts, JA Benjamin, L Tan, XL Manseau, EJ Dvorak, AM Dvorak, HF AF Nagy, JA Vasile, E Feng, D Sundberg, C Brown, LF Detmar, MJ Lawitts, JA Benjamin, L Tan, XL Manseau, EJ Dvorak, AM Dvorak, HF TI Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE VEGF-C; VEGF-D; PIGF; VPF/VEGF; VEGF-A ID CROHNS-DISEASE; LYMPHATIC ENDOTHELIUM; TYROSINE KINASES; FACTOR RECEPTORS; FACTOR VEGF; SKIN; PROLIFERATION; EXPRESSION; INDUCTION; TUMORS AB Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A(164), we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A-expressing tumors. We now report that, in addition to inducing angiogenesis, VEGF-A(164) also induces a strong lymphangiogenic response. This finding was unanticipated because lymphangiogenesis has been thought to be mediated by other members of the VPF/VEGF family, namely, VEGF-C and VEGF-D. The new "giant" lymphatics generated by VEGF-A(164) were structurally and functionally abnormal: greatly enlarged with incompetent valves, sluggish flow, and delayed lymph clearance. They closely resembled the large lymphatics found in lymphangiomas/lymphatic malformations, perhaps implicating VEGF-A in the pathogenesis of these lesions. Whereas the angiogenic response was maintained only as long as VEGF-A was expressed, giant lymphatics, once formed, became VEGF-A independent and persisted indefinitely, long after VEGF-A expression ceased. These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02215 USA. RP Dvorak, HF (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [CA 50453, CA 69184, CA 91861, P01 CA 92644, P01 CA092644, R01 CA050453, R01 CA069184, R01 CA086410]; NHLBI NIH HHS [HL 59316]; NIAID NIH HHS [AI 33372, AI 44066, R01 AI033372] NR 40 TC 339 Z9 357 U1 2 U2 10 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 DEC 2 PY 2002 VL 196 IS 11 BP 1497 EP 1506 DI 10.1084/jem.20021244 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 623AZ UT WOS:000179682000010 PM 12461084 ER PT J AU Dechant, EJ Beresin, EV Bostic, JQ AF Dechant, EJ Beresin, EV Bostic, JQ TI From elephant man to Jerry Springer - The rise of the psychological tele-spectacle SO ACADEMIC PSYCHIATRY LA English DT Article AB In the circus sideshow, people with physical deformities were exhibited for profit and entertainment. The circus sideshow itself is no longer socially acceptable, but it has taken a different form. Television programs like The Jerry Springer Show make spectacles of psychological afflictions and variations in human behavior. On the one hand, these shows provide participants with attention, recognition, an outlet for masochism, and an identity. To the viewer, they offer both reassurance and an outlet for unacceptable thoughts and feelings. They also explore society's collective subconscious. On the other hand, these shows approximate psychological interventions without concern for the result, have potentially negative consequences for vulnerable viewers, and blur the boundary between fantasy and real life. C1 McLean Hosp, MGH, Child & Adolescent Residency Training Program, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dechant, EJ (reprint author), Massachusetts Gen Hosp, Sch Psychiat, WAC 725, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD WIN PY 2002 VL 26 IS 4 BP 262 EP 266 DI 10.1176/appi.ap.26.4.262 PG 5 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 618DJ UT WOS:000179402800007 PM 12824130 ER PT J AU DiPiro, PJ vanSonnenberg, E Tumeh, SS Ros, PR AF DiPiro, PJ vanSonnenberg, E Tumeh, SS Ros, PR TI Volume and impact of second-opinion consultations by radiologists at a tertiary care cancer center: Data SO ACADEMIC RADIOLOGY LA English DT Article DE radiology and radiologists; radiology and radiologists, departmental management; oncology ID PROSTATE BIOPSIES; COST AB Rationale and Objectives. Patients with cancer who are referred to a dedicated oncology center usually have undergone previous imaging studies that the oncologists typically desire to have reviewed by radiologists. Such reinterpretations can be complex and time-consuming, yet many institutions do not systematically account for them as part of the total workload. The purpose of this study was to ascertain the numbers and types of second-opinion consultations performed by radiologists at a tertiary care cancer center, and to assess their effect on work volume. Materials and Methods. A survey of referring clinicians was undertaken to evaluate the numbers and types of second-opinion consultations requested of radiologists at the Dana Farber Cancer Institute during a 12-month period. Consultations included review of studies from outside institutions, and cases from Dana Farber in which further comparison was needed. The number of consultations requiring additional tumor size measurements was tallied. The mean daily number of new studies interpreted by radiologists was used as a benchmark of work volume. Results. Radiologists performed 4,664 consultations during 254 workdays, interpreting a mean of 18 additional studies (range, 4-42) per day as a result of referrals for second opinion. These included 3,638 (78%) cross-sectional studies (ie, computed tomographic [CT], magnetic resonance [MR], and ultrasound [US] studies), 674 (14%) mammograms, 220 (5%) plain radiographs, 132 (3%) nuclear medicine scans, and one galactogram. Of the 4,664 consultations, 1,306 (28%) were performed to obtain tumor measurements, many of these involving five to 10 bidimensional calculations per study. A mean of 101 new examinations per day was performed by radiologists during the same 12-month period, including cross-sectional studies (CT and US scans) (56%), plain radiographs (34%), and mammograms (11%). MR imaging was not performed. Conclusion. Second-opinion consultations increased the average daily work volume by 18%. This has implications for workforce, as well as for compensation in terms of relative value units and finances for this previously unquantified service. C1 Harvard Univ, Sch Med, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Piedmont Hosp, Dept Radiol, Atlanta, GA USA. RP DiPiro, PJ (reprint author), Harvard Univ, Sch Med, Dept Radiol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 21 Z9 21 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2002 VL 9 IS 12 BP 1430 EP 1433 DI 10.1016/S1076-6332(03)80671-2 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 638HC UT WOS:000180564700010 PM 12553355 ER PT J AU Fu, SC Chan, BP Wang, W Pau, HM Chan, KM Rolf, CG AF Fu, SC Chan, BP Wang, W Pau, HM Chan, KM Rolf, CG TI Increased expression of matrix metalloproteinase 1 (MMP1) in 11 patients with patellar tendinosis SO ACTA ORTHOPAEDICA SCANDINAVICA LA English DT Article ID TISSUE INHIBITOR; ACHILLODYNIA; ZYMOGRAPHY AB We studied the expression of procollagen type 1, matrix metalloproteinase 1 (MMP1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) by immunohistochemistry in human patellar tendinosis tissues and healthy patellar tendons. In situ gelatin zymography was used to detect collagenolytic activities. The productions of NMP1, TIMP1 and gelatinolytic activities were compared in cell cultures from tendinosis samples and controls. Tendinosis tissues and cultures showed an increase in the expression level of MMP1 and a decrease in that of TIMP1, a condition favoring collagen degradation. Gelatinolytic activities in tendinosis tissues and cultures were elevated. Collagenolysis is a striking feature in patellar tendinosis. C1 Chinese Univ Hong Kong, Dept Orthopaed & Traumatol, Shatin, Hong Kong, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Univ Sheffield, Sheffield Ctr Sports Med, Sheffield, S Yorkshire, England. RP Fu, SC (reprint author), Chinese Univ Hong Kong, Dept Orthopaed & Traumatol, Shatin, Hong Kong, Peoples R China. NR 19 TC 56 Z9 57 U1 1 U2 5 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6470 J9 ACTA ORTHOP SCAND JI Acta Orthop. Scand. PD DEC PY 2002 VL 73 IS 6 BP 658 EP 662 DI 10.3109/17453670209178031 PG 5 WC Orthopedics SC Orthopedics GA 630DA UT WOS:000180091200010 PM 12553513 ER PT J AU Nicholas, PK Kemppainen, JK Holzemer, WL Nokes, KM Eller, LS Corless, IB Bunch, EH Bain, CA Kirksey, KM Davis, SM Goodroad, BK AF Nicholas, PK Kemppainen, JK Holzemer, WL Nokes, KM Eller, LS Corless, IB Bunch, EH Bain, CA Kirksey, KM Davis, SM Goodroad, BK TI Self-care management for neuropathy in HIV disease SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID PERIPHERAL NEUROPATHY; NEUROLOGIC MANIFESTATIONS; INFECTED PATIENTS; COMPLICATIONS; THERAPY AB Peripheral neuropathy is the most common neurological complication in HIV and is often associated with antiretroviral therapy. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of peripheral neuropathy in HIV disease, the self-care strategies, and sources of information for self-care utilized by the sample. A convenience sample of 422 respondents was recruited from an Internet web-based site developed by the University of California, San Francisco International HIV/AIDS Research Network and from five geographic data collection sites ( Boston, New York City, San Francisco and Paterson in the USA, and Oslo, Norway). Results of the study indicated that respondents with peripheral neuropathy identified 77 self-care behaviours including complementary therapies, use of medications, exercise and rest and/or elevation of extremities. Sources of information included health care providers, informal networks and media sources. C1 MGH Inst Hlth Profess, Grad Program Nursing, Boston, MA 02129 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. CUNY Hunter Coll, New York, NY 10021 USA. Rutgers State Univ, Newark, NJ 07102 USA. Univ Oslo, N-0316 Oslo, Norway. Calif State Univ Fresno, Fresno, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nicholas, PK (reprint author), MGH Inst Hlth Profess, Grad Program Nursing, 36 1st Ave, Boston, MA 02129 USA. OI Corless, Inge/0000-0003-0438-2037 NR 26 TC 24 Z9 25 U1 0 U2 1 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids/Hiv PD DEC PY 2002 VL 14 IS 6 BP 763 EP 771 DI 10.1080/0954012021000031831 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 622QN UT WOS:000179657900003 PM 12511209 ER PT J AU Walsh, CR O'Donnell, CJ Camargo, CA Giugliano, RP Lloyd-Jones, DM AF Walsh, CR O'Donnell, CJ Camargo, CA Giugliano, RP Lloyd-Jones, DM TI Elevated serum creatinine is associated with 1-year mortality after acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID STAGE RENAL-DISEASE; COOPERATIVE CARDIOVASCULAR PROJECT; CORONARY-ARTERY DISEASE; LONG-TERM SURVIVAL; RANDOMIZED TRIAL; ELDERLY PATIENTS; HEART-DISEASE; RISK-FACTORS; DYSFUNCTION; REVASCULARIZATION AB Background Cardiovascular mortality is high in individuals with end-stage renal disease. However, less is known about the prognostic importance of moderate, renal insufficiency in patients with acute myocardial infarction. Methods We studied all patients with acute myocardial infarction admitted through the emergency department to an urban, academic hospital over 1 year. Patients were classified as having elevated (> 133 mumol/L [1.5 mg/dL]) or normal 133 mumol/L) serum creatinine at presentation. Results Of 483 patients, 22% had elevated creatinine and 786/. had normal creatinine. By 1 year, 46% of patients with elevated creatinine and 15% of patients with normal creatinine had died (P < .001). The unadjusted hazard ratio for 1-year mortality was increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 3.85, 95% CI 2.61-5.67). After adjustment for baseline characteristics and treatment, the multivariable-adjusted hazard ratio for 1-year mortality remained increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 2.40, 95% CI 1.55-3.72). There was an important modification of the prognostic value of creatinine by the presence of congestive heart failure at presentation (P value for interaction =.04). The adjusted hazard ratio for 1-year death associated with elevated creatinine compared with normal creatinine was 3.89 (95% CI 1.87-8.07) in patients without congestive heart failure and 1.92 (95% CI 1.10-3.36) in patients with congestive heart failure. Conclusions Elevated serum creatinine at presentation is associated with 1-year mortality, after acute myocardial infarction. Further study is needed to optimize treatment after myocardial infarction in this high-risk group. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. RP O'Donnell, CJ (reprint author), Premium Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [HL-03533, HL-07575] NR 38 TC 68 Z9 73 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 DEC PY 2002 VL 144 IS 6 BP 1003 EP 1011 DI 10.1067/mhj.2002.125504 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 631UY UT WOS:000180186200009 PM 12486424 ER PT J AU Januzzi, JL Cannon, CP DiBattiste, PM Murphy, S Weintraub, W Braunwald, E AF Januzzi, JL Cannon, CP DiBattiste, PM Murphy, S Weintraub, W Braunwald, E CA TACTICS-TIMI 18 Investigators TI Effects of renal insufficiency on early invasive management in patients with acute coronary syndromes (The TACTICS-TIMI 18 trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FAILURE; DISEASE AB Among patients in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS)-Thrombolysis In Myocardial Infarction (TIMI) 18 study, decreasing renal function was associated with an increased prevalence of high-risk clinical findings, more extensive coronary artery disease, and independently associated with a high rate of adverse ischemic events after non-ST-segment elevation acute coronary syndrome (NSTE ACS). Across the range of renal function among patients in TACTICS-TIMI 18, the use of tirofiban plus an early invasive strategy was superior to conservative, ischemia-guided NSTE ACS management. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Merck Res Labs, W Point, PA USA. Emory Univ, Atlanta, GA 30322 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. TIMI Study Grp, Boston, MA USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bldg 019, Boston, MA 02114 USA. NR 13 TC 73 Z9 78 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 DEC 1 PY 2002 VL 90 IS 11 BP 1246 EP + AR PII S0002-9149(02)02844-8 DI 10.1016/S0002-9149(02)02844-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 621YN UT WOS:000179618800014 PM 12450608 ER PT J AU Gogas, H Paterakis, G Frangia, K Bafaloukos, D Pectasides, D Kalofonos, HP Loukopoulos, D Stavropoulou-Giokas, C Ioannovich, J Mihm, MC AF Gogas, H Paterakis, G Frangia, K Bafaloukos, D Pectasides, D Kalofonos, HP Loukopoulos, D Stavropoulou-Giokas, C Ioannovich, J Mihm, MC TI Lymphocyte subpopulations and interleukin levels in high-risk melanoma patients treated with high-dose interferon A-2B SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE adjuvant melanoma therapy; interferon; lymphocyte subpopulations; interleukins ID RENAL-CELL CARCINOMA; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; ADJUVANT THERAPY; ALPHA; TRIAL; COMBINATION AB Immunologic effects of high-dose interferon are still unclear. We have evaluated changes in blood lymphocyte subpopulations, immunoglobulins, and multiple interleukin in patients with high-risk cutaneous melanoma on adjuvant treatment with high-dose interferon and compared pretreatment values with normal controls. Samples were obtained before treatment, I month after induction treatment and at 3, 6, and 12 months of maintenance treatment from 24 patients with high-risk melanoma. Lymphocyte subpopulations were measured by flow cytometry and interleukin and immunoglobulin levels by radioimmunoassay. A statistically significant reduction in Blymphocytes (p < 0.001), natural killer (NK) cells (p = 0.0004), and monocytes (p = 0.04), and an elevation in CD4/ CD8 ratio (p < 0.0001) was observed after I month of intravenous interferon. No changes were seen in CD3, CD4, and CD8 lymphocytes. No changes in interleukin (IL)-2, -4, or -5 were observed during 1 year of treatment. IL-2 pretreatment levels were significantly lower than healthy blood donors (P = 0.001), and IL-5 pretreatment levels were significantly higher (p = 0.0056). IL-10 levels significantly dropped after 6 months of treatment (p = 0.01). Immunoglobulins (IgG, IgA, IgM) remained within normal ranges. Three patients had elevated pretreatment levels of IgE. There is a time- and dose-dependent impact of interferon on numbers of circulating B lymphocytes, NK cells, monocytes, and CD4/CD8 ratio. Defects in cellular and humoral immunity are suggested by the low IL-2 and high IL-5 levels, measured in patients with melanoma as compared with healthy controls. C1 Univ Athens, Laiko Hosp, Dept Internal Med 1, Athens, Greece. Gen Hosp Athens, Dept Immunol, Athens, Greece. Gen Hosp Athens, Natl Tissue Typing Ctr, Athens, Greece. Gen Hosp Athens G Gennimatas, Dept Plast Surg & Microsurg, Athens, Greece. Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. RP Gogas, H (reprint author), POB 14120, Athens 11510, Greece. OI Kalofonos, Haralabos/0000-0002-3286-778X NR 17 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 2002 VL 25 IS 6 BP 591 EP 596 DI 10.1097/00000421-200212000-00013 PG 6 WC Oncology SC Oncology GA 627VC UT WOS:000179956000013 PM 12478006 ER PT J AU Kratz, A Lewandrowski, KB Siegel, AJ Chun, KY Flood, JG Van Cott, EM Lee-Lewandrowski, E AF Kratz, A Lewandrowski, KB Siegel, AJ Chun, KY Flood, JG Van Cott, EM Lee-Lewandrowski, E TI Effect of marathon running on hematologic and biochemical laboratory parameters, including cardiac markers SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE laboratory; clinical chemistry; hematology; marathon; sports medicine; reference values ID RUNNERS; PLASMA; COMPONENTS; FLUID; RACE AB Participants in marathon races may require medical attention and the performance of laboratory assays. We report the changes in basic biochemical parameters, cardiac markers, CBC counts, and WBC differentials observed in participants in a marathon before, within 4 hours, and 24 hours after a race. The concentrations of glucose, total protein, albumin, uric acid, calcium, phosphorus, serum urea nitrogen, creatinine, bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total creatine kinase, creatine kinase-MB, myoglobin, and the anion gap were increased after the race, consistent with the effects of exertional rhabdomyolysis and hemolysis. The increase in WBC counts was due mainly to neutrophilia and monocytosis, with a relative decrease in circulating lymphocytes, consistent with an inflammatory reaction to tissue injury. A significant percentage of laboratory results were outside the standard reference ranges, indicating that modified reference ranges derived from marathon runners might be more appropriate for this population. We provide a table of modified reference ranges (or expected ranges) for basic biochemical, cardiac, and hematologic laboratory parameters for marathon runners. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Dept Med, Belmont, MA 02178 USA. RP Lee-Lewandrowski, E (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, 55 Fruit St,GRB5, Boston, MA 02114 USA. NR 31 TC 117 Z9 118 U1 2 U2 8 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 2002 VL 118 IS 6 BP 856 EP 863 DI 10.1092/BTWQ5YMYVQ67QK9L PG 8 WC Pathology SC Pathology GA 619JA UT WOS:000179471800006 PM 12472278 ER PT J AU Sheffield, MV Yee, H Dorvault, CC Weilbaecher, KN Eltoum, IA Siegal, GP Fisher, DE Chhieng, DC AF Sheffield, MV Yee, H Dorvault, CC Weilbaecher, KN Eltoum, IA Siegal, GP Fisher, DE Chhieng, DC TI Comparison of five antibodies as markers in the diagnosis of melanoma in cytologic preparations SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 23-MAR 01, 2002 CL CHICAGO, ILLINOIS SP US & Canadian Acad Pathol DE microphthalmia transcription factor; Melan-A; tyrosinase; S-100; HMB-45; melanoma; immunocytochemistry; cytology ID MICROPHTHALMIA TRANSCRIPTION FACTOR; METASTATIC MALIGNANT-MELANOMA; NEEDLE ASPIRATION BIOPSY; HMB-45 MONOCLONAL-ANTIBODY; PARAFFIN-EMBEDDED TISSUES; S-100 PROTEIN; IMMUNOHISTOCHEMICAL DIAGNOSIS; AMELANOTIC MELANOMAS; MELANOCYTIC LESIONS; FACTOR FAMILY AB We determined the sensitivity and specificity of 3 novel antibodies (microphthalmia transcription factor [Mitf] Melan-A, and tyrosinase) as markers for melanoma in cytologic preparations and compared the results with those of commonly used markers (S-100 protein [S-100] and HMB-45). We stained 72 cell blocks from 40 patients with melanoma and 32 with nonmelanocytic malignant neoplasms with antibodies against S-100, HMB-45, Mitf, Melan-A, and tyrosinase. Histologic correlation was available in more than 95% of cases. Nuclear staining for Mitf and cytoplasmic staining for S-100, HMB-45, Melan-A, and tyrosinase in more than 10% of tumor cells was considered positive. All 3 novel markers demonstrated sensitivity superior to S-100 and HMB-45. HMB-45, Melan-A, and Mitf demonstrated specificities of 97%. S-100 protein and tyrosinase were less specific. Sensitivity and specificity for the combination Mitf+/Melan-A+ were 95% and 100%, respectively, whereas they were 80% and 100%, respectively, for S-100+/HMB-45+. Mitf, Melan-A, and tyrosinase are sensitive markers for epithelioid melanoma. Mitf and Melan-A seem more specific than S-100 and tyrosinase. An antibody panel consisting of Mitf and Melan-A is superior to a panel of S-100 and HMB-45 in the diagnosis of melanoma in cytologic specimens. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35249 USA. NYU, Ctr Med, Dept Pathol, New York, NY USA. Lee Pathol Lab, Opelika, AL USA. Washington Univ, Div Oncol, St Louis, MO USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Chhieng, DC (reprint author), Univ Alabama, Dept Pathol, Birmingham, AL 35249 USA. NR 56 TC 50 Z9 53 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 2002 VL 118 IS 6 BP 930 EP 936 DI 10.1092/AU8L65UJFQ75DVGC PG 7 WC Pathology SC Pathology GA 619JA UT WOS:000179471800015 PM 12472287 ER PT J AU Luck, J Peabody, JW AF Luck, J Peabody, JW TI When do developing countries adopt managed care policies and technologies? Part II: Infrastructure, techniques, and reform strategies SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH SYSTEM REFORM; TRANSITION; BRAZIL; SECTOR; MARKET; CHINA; COSTS AB Objectives: To specify the essential infrastructure elements required to-implement managed care techniques successfully in a developing country, once the necessary macroeconomic preconditions for managed care have been met. Also, to describe how managed care techniques can be integrated into health system reform strategies. Study Design and Methods: Analysis of available developing country health system and healthcare spending data, review of the available literature, and authors' experience evaluating healthcare reform in developing countries. Results: Successful managed care relationships among payers, providers, and patients rely on several essential infrastructure elements: enabling legislation; regulatory mechanisms to administratively, correct health and insurance market failures; enforceable contracts; and formal groups or associations of providers. Once these infrastructure elements are in place, a developing country government can consider implementing 1 or more managed care techniques, including payment strategies, demand-side techniques, and utilization management. Conclusions: Governments in many developing countries can take deliberate steps to accelerate the evolution of certain macroeconomic preconditions-human capital and information systems-and essential infrastructure elements necessary to support managed care techniques. They may then choose to experiment carefully with implementing specific managed care techniques, with consideration given to how the managed care techniques can promote primary care. C1 Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, Inst Global Hlth, San Francisco, CA 94105 USA. Univ Calif Los Angeles, Sch Publ Hlth, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA 90407 USA. RP Peabody, JW (reprint author), Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, Inst Global Hlth, 74 New Montgomery St,Suite 508, San Francisco, CA 94105 USA. NR 43 TC 3 Z9 3 U1 1 U2 2 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 DEC PY 2002 VL 8 IS 12 BP 1093 EP 1103 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 626LE UT WOS:000179873100006 PM 12500885 ER PT J AU Ransohoff, DF McNaughton Collins, M Fowler, FJ AF Ransohoff, DF McNaughton Collins, M Fowler, FJ TI Why is prostate cancer screening so common when the evidence is so uncertain? A system without negative feedback SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID RADICAL PROSTATECTOMY; INFORMED CONSENT; ANTIGEN; OUTCOMES; PHYSICIANS; UROLOGISTS; DECISION AB The degree of enthusiasm for prostate cancer screening seems high given the limited evidence of benefit and the well-documented harms of treatment that include impotence and incontinence. The purpose of this review is to understand the reasons for enthusiasm and positive reinforcement perceived in clinical decisions about whether to screen, whether to choose aggressive therapy for cancer, and in how to view adverse effects following therapy. We discuss a case of a man who must decide whether to undergo prostate-specific antigen screening and treatment to illustrate the kinds of reinforcement that may occur for each decision. Strong positive reinforcement for each decision would make screening and aggressive therapy appear to be successful and the correct decision even if prostate cancer screening and I therapy were not beneficial. A physician is positively reinforced for recommending screening, regardless of the test result, because a negative result makes a patient grateful for reassurance and a positive result makes a patient grateful for early detection. A patient who is impotent and incontinent after a decision for curative treatment may attribute his survival to surgery and be grateful for having his cancer cured. Individual experience provides almost no negative feedback that early detection and aggressive treatment may not work. Although reinforcement operates similarly in other medical decisions, the example of prostate cancer provides insight into the strength of the forces at work because the personal harms, which are relatively common and dramatic, are readily discounted or explained away. Even if prostate cancer screening is eventually demonstrated to provide benefit for asymptomatic persons, it is important to appreciate the strength of forces that may act independently of benefit and reinforce decision makers' choices to e aggressive about screening and treatment. Interventions should be considered to temper possible overenthusiasm for screening and treatment. (C)2002 by Excerpta Medica, Inc. C1 Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Massachusetts Gen Hosp, Med Serv, Div Gen Med, Boston, MA USA. RP Ransohoff, DF (reprint author), Univ N Carolina, Dept Med, 724 Burnett Womack Bldg,CB 7080, Chapel Hill, NC 27599 USA. FU AHRQ HHS [HS 08397] NR 34 TC 82 Z9 83 U1 0 U2 2 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 DEC 1 PY 2002 VL 113 IS 8 BP 663 EP 667 AR PII S0002-9343(02)01235-4 DI 10.1016/S0002-9343(02)01235-4 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 631CQ UT WOS:000180150000007 PM 12505117 ER PT J AU Snow, KK Cote, J Yang, WN Davis, NJ Seddon, JM AF Snow, KK Cote, J Yang, WN Davis, NJ Seddon, JM TI Association between reproductive and hormonal factors and age-related maculopathy in postmenopausal women SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; MACULAR DEGENERATION; RISK-FACTORS; CARDIOVASCULAR-DISEASE; REPLACEMENT THERAPY; LENS OPACITIES; PREVALENCE; MORTALITY; ESTROGENS; CATARACTS AB PURPOSE: The relationships between reproductive risk factors, including use of hormone replacement therapy and oral contraceptives and severity of age,related maculopathy (ARM) among postmenopausal women were evaluated. We hypothesized that exposure to endogenous or exogenous estrogens would be associated with a reduced risk of advanced ARM. DESIGN. Cross-sectional study. METHODS: The 394 subjects were postmenopausal women with ARM. Logistic regression analysis was used to compare the effects of several reproductive factors across two groups: 193 subjects with nonadvanced ARM and 201 subjects with advanced ARM. RESULTS: Women with ARM who had used postmenopausal estrogen therapy in the past had significantly lower odds of advanced ARM than nonusers, after controlling for other known and potential risk factors (odds ratio [OR] = 0.5, 95% confidence interval [Cl] = 0.30 to 0.98). Older age at menarche was associated with increased odds of advanced ARM (OR = 1.16, 95% CI 1.00 to 1.35). CONCLUSIONS: These findings suggest that exposure to exogenous estrogens may have a beneficial effect of reducing the risk of advanced types of ARM in postmenopausal women with ARM. Few therapeutic or preventive measures currently exist for ARM; therefore, these results deserve further evaluation. C1 Massachusetts Eye & Ear Infirm, Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Seddon, JM (reprint author), Massachusetts Eye & Ear Infirm, Epidemiol Unit, 243 Charles St, Boston, MA 02114 USA. NR 29 TC 31 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2002 VL 134 IS 6 BP 842 EP 848 AR PII S0002-9394(02)01755-5 DI 10.1016/S0002-9394(02)01755-5 PG 7 WC Ophthalmology SC Ophthalmology GA 624BA UT WOS:000179738600007 PM 12470752 ER PT J AU Schmidt, EV AF Schmidt, EV TI Genes involved in breast cancer progression - Analysis of global changes in gene expression or retroviral tagging? SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID MAMMARY-TUMOR VIRUS; TRANSGENIC MICE; CYCLIN D1; PROVIRAL INSERTION; HETEROZYGOSITY; CARCINOMA; ADENOCARCINOMAS; TRANSFORMATION; TUMORIGENESIS; HYPERPLASIA C1 Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Serv Pediat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Dept Pediat, 13th St,Bldg 149,7th Fl, Charlestown, MA 02129 USA. NR 33 TC 4 Z9 5 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2002 VL 161 IS 6 BP 1973 EP 1977 DI 10.1016/S0002-9440(10)64473-2 PG 5 WC Pathology SC Pathology GA 622TP UT WOS:000179663400002 PM 12466111 ER PT J AU Poulaki, V Mitsiades, CS Joussen, AM Lappas, A Kirchhof, B Mitsiades, N AF Poulaki, V Mitsiades, CS Joussen, AM Lappas, A Kirchhof, B Mitsiades, N TI Constitutive nuclear factor-kappa B activity is crucial for human retinoblastoma cell viability SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACTIVATED PROTEIN-KINASE; ALPHA-INDUCED APOPTOSIS; CASPASE-INDEPENDENT PATHWAY; CYTOCHROME-C RELEASE; TNF-ALPHA; Y79 CELLS; SODIUM-BUTYRATE; BCL-X; MEDIATED APOPTOSIS AB Retinoblastoma (Rb) is the most common intraocular malignancy of childhood. Although systemic and intrathecal chemotherapy with local and cranial radiotherapy have improved overall survival, the prognosis for patients with central nervous system involvement is still poor. We investigated the role of the transcription factor nuclear factor (NF)-kappaB, which promotes cell survival in several other models, in the pathophysiology of Rb. The human Rb cell fines Y79 and WERI-Rb1 were treated with the cell permeable peptide SN50, that specifically inhibits the transcriptional activity of NF-kappaB by blocking its translocation into the nucleus. We found that NF-kappaB inhibition up-regulated Bax; down-regulated the anti-apoptotic proteins Bcl-2, A1, and cIAP-2; and induced loss of the mitochondrial transmembrane potential and caspase-independent, calpain-dependent apoptosis in Rb cells. Inhibition of the P38 kinase sensitized cells to SN50-induced cell death, whereas insulin-like growth factor-1 activated NF-kappaB and attenuated the proapoptotic effect of SN50. Finally, NF-kappaB inhibition sensitized Rb cells to doxorubicin. In conclusion, inhibition of NF-kappaB activity in Rb cells leads to loss of mitochondrial transmembrane potential and caspase-independent, calpain-dependent apoptosis. Therapeutic strategies targeting NF-kappaB could be beneficial in the clinical management of Rb, either alone or in combination with conventional chemotherapy. C1 Univ Cologne, Zentrum Mol Med, Ctr Mol Med, Cologne, Germany. Univ Cologne, Ctr Ophthalmol, Cologne, Germany. Univ Cologne, Dept Vitreoretinal Surg, Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Retina Res Lab, Boston, MA 02114 USA. RP Poulaki, V (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Res & Angiogenesis Lab, 325 Cambridge St, Boston, MA 02114 USA. NR 77 TC 30 Z9 30 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2002 VL 161 IS 6 BP 2229 EP 2240 DI 10.1016/S0002-9440(10)64499-9 PG 12 WC Pathology SC Pathology GA 622TP UT WOS:000179663400028 PM 12466137 ER PT J AU Stoppani, J Hildebrandt, AL Sakamoto, K Cameron-Smith, D Goodyear, LJ Neufer, PD AF Stoppani, J Hildebrandt, AL Sakamoto, K Cameron-Smith, D Goodyear, LJ Neufer, PD TI AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE 5-aminoimidazole-4-carboxamide ribonucleoside; single-leg arterial infusion; rat; AMP kinase phosphorylation ID FAST-TWITCH MUSCLE; SACCHAROMYCES-CEREVISIAE; CREATINE-KINASE; GLUCOSE-UPTAKE; BETA-GPA; IN-VITRO; EXPRESSION; EXERCISE; GLUT-4; NUCLEAR AB AMP-activated protein kinase (AMPK) has recently emerged as a key signaling protein in skeletal muscle, coordinating the activation of both glucose and fatty acid metabolism in response to increased cellular energy demand. To determine whether AMPK signaling may also regulate gene transcription in muscle, rats were given a single subcutaneous injection (1 mg/g) of the AMP analog 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR). AICAR injection activated (P < 0.05) AMPK-(α2) (&SIM;2.5-fold) and transcription of the uncoupling protein-3 (UCP3, &SIM;4-fold) and hexokinase II (HKII, &SIM;10-fold) genes in both red and white skeletal muscle. However, AICAR injection also elicited (P < 0.05) an acute drop (60%) in blood glucose and a sustained (2-h) increase in blood lactate, prompting concern regarding the specificity of AICAR on transcription. To maximize AMPK activation in muscle while minimizing potential systemic counterregulatory responses, a single-leg arterial infusion technique was employed in fully conscious rats. Relative to saline-infused controls, single-leg arterial infusion of AICAR (0.125, 0.5, and 2.5 mug.g(-1).min(-1) for 60 min) induced a dose-dependent increase (2- to 4-fold, P < 0.05) in UCP3 and HKII transcription in both red and white skeletal muscle. Importantly, AICAR infusion activated transcription only in muscle from the infused leg and had no effect on blood glucose or lactate levels. These data provide evidence that AMPK signaling is linked to the transcriptional regulation of select metabolic genes in skeletal muscle. C1 John B Pierce Fdn Lab, New Haven, CT 06519 USA. Yale Univ, Dept Cellular & Mol Physiol, New Haven, CT 06519 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Neufer, PD (reprint author), John B Pierce Fdn Lab, 290 Congress Ave, New Haven, CT 06519 USA. FU NIAMS NIH HHS [AR-42338, AR-45670, AR-45372] NR 55 TC 65 Z9 66 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 2002 VL 283 IS 6 BP E1239 EP E1248 DI 10.1152/ajpendo.00278.2002 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 612MP UT WOS:000179080300017 PM 12388122 ER PT J AU Martinez, V Barrachina, MD Ohning, G Tache, Y AF Martinez, V Barrachina, MD Ohning, G Tache, Y TI Cephalic phase of acid secretion involves activation of medullary TRH receptor subtype 1 in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE gastrin; atropine; nitro-L-arginine methyl ester; indomethacin; glycine-gastrin antibody; antisense oligodeoxynucleotides; 2-deoxy-D-glucose; histamine ID THYROTROPIN-RELEASING-HORMONE; DORSAL MOTOR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; GASTRIC-ACID; VAGAL COMPLEX; NUTRITIONAL IMPLICATIONS; INTRACISTERNAL TRH; RESPONSES; VAGUS; STIMULATION AB Mechanisms involved in the cephalic phase of gastric acid secretion were studied in awake fasted rats with chronic gastric fistula and exposed to the sight and smell of chow for 30 min. Acid secretion was monitored using constant intragastric perfusion and automatic titration. Sham feeding induced a peak acid response reaching 82 +/- 7 mumol/10 min within 20 min compared with the average 22 +/- 2 mumol/10 min in controls. The sham-feeding response was abolished by intracisternal pretreatment with the TRH1-receptor antisense oligodeoxynucleotides or subcutaneous injection of atropine, whereas TRH1 mismatch oligodeoxynucleotides had no effect. Serum gastrin was not altered by the sham feeding and increased by refeeding. Gastrin antibody did not block the rise in acid during sham feeding, although the net acid response was reduced by 47% compared with the control group. Glycine-gastrin antibody, indomethacin and nitro-L-arginine methyl ester had no effect. Atropine and gastrin antibody decreased basal acid secretion by 98 and 75%, respectively, whereas all other pretreatments did not. These results indicate that the cholinergic-dependent acid response to sham feeding is mediated by brain medullary TRH1 receptors in rats. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Div Digest Dis, CURE Digest Dis Res Ctr, Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-30110, DK-41301] NR 56 TC 18 Z9 19 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD DEC PY 2002 VL 283 IS 6 BP G1310 EP G1319 DI 10.1152/ajpgi.00222.2002 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 615KM UT WOS:000179244400012 PM 12388176 ER PT J AU Chaudhri, B Del Monte, F Hajjar, RJ Harding, SE AF Chaudhri, B Del Monte, F Hajjar, RJ Harding, SE TI Interaction between increased SERCA2a activity and beta-adrenoceptor stimulation in adult rabbit myocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE phospholamban; antisense; aftercontraction; arrhythmia ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; PIG VENTRICULAR MYOCYTES; ADENOVIRAL GENE-TRANSFER; HEART-FAILURE; TROPONIN-I; PHOSPHOLAMBAN; CALCIUM; CONTRACTILITY; PHOSPHORYLATION; AFTERCONTRACTIONS AB Sarco(endo)plasmic reticulum. Ca2+-ATPase (SERCA)2a overexpression and phospholamban depletion have been shown to have beneficial effects on contractility in heart failure. However, the high sympathetic tone during development of failure may interact with increases in SERCA2a activity in potentially deleterious ways. We used adenoviral vectors to overexpress SERCA2a or partially downregulate phospholamban in adult rabbit ventricular myocytes in culture and studied the responses of these cells to beta-adrenoceptor stimulation. SERCA2a overexpression and phospholamban depletion had quantitatively similar effects on basal contraction amplitude and in accelerating relaxation. Increasing SERCA2a activity by either strategy had little effect on the increase in contraction amplitude or incidence of arrhythmias with increasing isoproterenol. Maximum acceleration of relaxation by beta-adrenoceptor stimulation was similar to that produced by SERCA2a overexpression. Isoproterenol treatment of SERCA2a-overexpressing or phospholamban-deficient myocytes produced a further modest decrease in relaxation time, with similar final values in both groups. We find no evidence for Ca2+ overload induced by SERCA2a overexpression alone or in combination with catecholamines. C1 Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst, London SW3 6LY, England. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Harding, SE (reprint author), Imperial Coll Sch Sci Technol & Med, NHLI, Dovehouse St, London SW3 6LY, England. NR 36 TC 12 Z9 14 U1 0 U2 1 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 DEC PY 2002 VL 283 IS 6 BP H2450 EP H2457 DI 10.1152/ajpheart.00391.2002 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 613XD UT WOS:000179156000036 PM 12388307 ER PT J AU Nemoto, S Defreitas, G Mann, DL Carabello, BA AF Nemoto, S Defreitas, G Mann, DL Carabello, BA TI Effects of changes in left ventricular contractility on indexes of contractility in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE contractile indexes; echocardiography; catheterization; mouse heart ID PRESSURE-VOLUME RELATION; FORCE-FREQUENCY RELATION; CONDUCTANCE CATHETER; ECHOCARDIOGRAPHY; MODULATION; MOUSE AB Measurement of left ventricular (LV) function is often overlooked in murine studies, which have been used to analyze the effects of genetic manipulation on cardiac phenotype. The goal of this study was to address the effects of changes in LV contractility on indexes of contractility in mice. LV function was assessed in vivo in closed-chest mice by echocardiography and by LV catheterization using a conductance pressure-volume (P-V) catheter with three different interventions that alter contractility by 1) atrial pacing to increase inotropy by augmentation of the force-frequency relation (modest increment of inotropy), 2) dobutamine to maximize inotropy, and 3) esmolol infusion to decrease contractility. Load-independent parameters derived from P-V relations, such as slope of end-systolic P-V relations (ESPVR) and slope of the first maximal pressure derivative over time (dP/dt(max))-end-diastolic volume relation (dP/dt-EDV), and standard echocardiographic parameters were measured. The dP/dt-EDV changed the most among parameters after atrial pacing and dobutamine infusion (percent change, 162.8 +/- 95.9% and 271.0 +/- 44.0%, respectively). ESPVR was the most affected by a decrease in LV contractility during esmolol infusion (percent change, -49.8 +/- 8.3%). However, fractional shortening failed to detect changes in contractility during atrial pacing and esmolol infusion and its percent change was <20%. This study demonstrated that contractile parameters derived from P-V relations change the most during a change in LV contractility and should therefore best detect a small change in contractility in mice. Heart rate has a modest but significant effect on P-V relationship-derived indexes and must be considered in the evaluation of murine cardiac physiology. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. RP Nemoto, S (reprint author), 2002 Holcombe Blvd,Bldg 110,Rm 151C, Houston, TX 77030 USA. NR 21 TC 45 Z9 45 U1 1 U2 4 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 DEC PY 2002 VL 283 IS 6 BP H2504 EP H2510 DI 10.1152/ajpheart.00765.2001 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 613XD UT WOS:000179156000043 PM 12427596 ER PT J AU Richardson, RD Omachi, K Kermani, R Woods, SC AF Richardson, RD Omachi, K Kermani, R Woods, SC TI Intraventricular insulin potentiates the anorexic effect of corticotropin releasing hormone in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE food intake; body weight; obesity; satiety ID HYPOTHALAMOPITUITARY-ADRENAL AXIS; MESSENGER-RNA EXPRESSION; CENTRAL-NERVOUS-SYSTEM; Y GENE-EXPRESSION; BODY-WEIGHT GAIN; FA FA RATS; FOOD-INTAKE; ARCUATE NUCLEUS; CEREBROSPINAL-FLUID; LEPTIN RECEPTOR AB Intraventricular corticotropin releasing hormone (CRH) suppresses food intake and body weight as a stress response. Insulin, acting within the brain, also suppresses food intake and body weight, and this suppression is related to caloric homeostasis. We determined if increased insulin within the brain potentiates the anorexic effects of intraventricular CRH. Rats were food deprived for 17 h each day and then given 30-min access to Ensure. One-half received continuous third ventricular infusion of synthetic cerebrospinal fluid via osmotic minipumps, and one-half received insulin (0.6 mU/day). During the infusion, rats also received 0, 0.1, 1.0, or 5.0 mug of CRH into the lateral ventricle just before access to Ensure. Insulin alone had no effect on Ensure intake or body weight. CRH dose dependently reduced Ensure intake in both groups, and the reduction was greater in the insulin group. Hence, central insulin potentiated the ability of centrally administered CRH to suppress food intake. These findings suggest that stress-related influences over food intake, particularly those mediated via CRH, interact with relative adiposity as signaled to the brain by central insulin. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Dent, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Tehran, Tehran, Iran. Univ Cincinnati, Med Ctr, Dept Psychiat, Cincinnati, OH 45267 USA. RP Woods, SC (reprint author), Univ Cincinnati, Med Ctr, Dept Psychiat, Box 670559, Cincinnati, OH 45267 USA. FU NIDDK NIH HHS [DK-17844] NR 78 TC 11 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 2002 VL 283 IS 6 BP R1321 EP R1326 DI 10.1152/ajpregu.00521.2001 PG 6 WC Physiology SC Physiology GA 614BW UT WOS:000179169300005 PM 12429558 ER PT J AU Sabolic I Ljubojevic, M Herak-Kramberger, CM Brown, D AF Sabolic, I Ljubojevic, M Herak-Kramberger, CM Brown, D TI Cd-MT causes endocytosis of brush-border transporters in rat renal proximal tubules SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cytoskeleton; heavy metals; immunocytochemistry; kidney; microtubules; nephrotoxicity ID CADMIUM-INTOXICATED RATS; MEMBRANE-VESICLES; METALLOTHIONEIN CDMT; CONVOLUTED TUBULES; ANTIGEN RETRIEVAL; TREATED RATS; MOUSE KIDNEY; IN-VITRO; CELLS; NEPHROTOXICITY AB Nephrotoxicity in humans and experimental animals due to chronic exposure to cadmium (Cd) is manifested by defects in the reabsorptive and secretory functions of proximal tubules (PT). The main symptoms of Cd nephrotoxicity, including polyuria, phosphaturia, aminoaciduria, glucosuria, and proteinuria, suggest that various brush-border membrane (BBM) transporters are the main targets of Cd. Specific transporters may be either directly inhibited by Cd or lost from the BBM after Cd treatment, or both. We have recently proposed that Cd may impair the vesicle-dependent recycling of BBM transporters by inhibiting vacuolar H(+)-ATPase (V-ATPase) activity and endocytosis in PT cells (Herak-Kramberger CM, Sabolic I, and Brown D. Kidney Int 53: 1713-1726, 1998). The mechanism underlying the Cd effect was further explored in an in vivo model of experimental Cd nephrotoxicity induced by Cd-metallothionein (CdMT; 0.4 mg Cd/kg body mass; a single dose sc) in rats. The time-dependent redistribution of various BBM transporters was examined in this model by fluorescence and gold-labeling immunocytochemistry on tissue sections and by immunoblotting of isolated renal cortical BBM. In PT cells of Cd-MT-treated rats, we observed 1) shortening and loss of microvilli; 2) time-dependent loss of megalin, V-ATPase, aquaporin-1 (AQP1), and type 3 Na(+)/H(+) exchanger (NHE3) from the BBM; 3) redistribution of these transporters into vesicles that were randomly scattered throughout the cell cytoplasm; and 4) redistribution of NHE3, but not megalin, into the basolateral plasma membrane. The internalization of BBM transporters was accompanied by fragmentation and loss of microtubules and by an increased abundance of alpha-tubulin monomers in PT cells. Transporter redistribution was detectable as early as 1 h after Cd-MT treatment and increased in magnitude over the next 12 h. We conclude that the early mechanism of Cd toxicity in PT cells may include a colchicine-like depolymerization of microtubules and impaired vesicle-dependent recycling of various BBM proteins. These processes may lead to a time-dependent loss of cell membrane components, resulting in reabsorptive and secretory defects that occur in Cd-induced nephrotoxicity. C1 Inst Med Res & Occupat Hlth, Unit Mol Toxicol, HR-10001 Zagreb, Croatia. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Sabolic I (reprint author), Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Ksaverska Cesta 2,POB 291, HR-10001 Zagreb, Croatia. EM sabolic@imi.hr FU FIC NIH HHS [1-R03-TW-01057-01]; NIDDK NIH HHS [DK-42956, DK-43351, DK-57521] NR 70 TC 35 Z9 35 U1 2 U2 6 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 DEC PY 2002 VL 283 IS 6 BP F1389 EP F1402 DI 10.1152/ajprenal.00006.2002 PG 14 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 613AA UT WOS:000179106600021 PM 12426237 ER PT J AU Senthil, D Choudhury, GG Abboud, HE Sonenberg, N Kasinath, BS AF Senthil, D Choudhury, GG Abboud, HE Sonenberg, N Kasinath, BS TI Regulation of protein synthesis by IGF-I in proximal tubular epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE phosphatidylinositol 3-kinase; mitogen-activated protein kinase; protein translation; eukaryotic initiation factor 4E; eIF4E binding protein ID GROWTH-FACTOR-I; INITIATION-FACTOR EIF-4E; FACTOR 4E-BINDING PROTEIN-1; SMOOTH-MUSCLE CELLS; TRANSLATION INITIATION; PHAS-I; MESSENGER-RNA; RENAL GROWTH; FACTOR 4E; UNINEPHRECTOMIZED RATS AB Protein synthesis is required for renal hypertrophy, and proximal tubular epithelial cells are an important cell type involved in this process. We examined IGF-I regulation of protein synthesis in murine proximal tubular epithelial (MCT) cells. We focused on initial events in protein translation and the signaling events involved. Translation of capped mRNAs is under the control of eukaryotic initiation factor 4E (eIF4E). In the resting cell, eIF4E is normally kept in an inactive state by binding to 4E-BP1, its binding protein. Phosphorylation of 4E-BP1 results in dissociation of the eIF4E-4E-BP1 complex allowing eIF4E to initiate peptide synthesis. IGF-I stimulated protein synthesis, augmented phosphorylation of 4E-BP1 and promoted the dissociation of eIF4E from 4E-BP1. IGF-I stimulated the activities of phosphatidylinositol (PI) 3-kinase, Akt, and ERK1/2-type MAPK in MCT cells. IGF-I-induced phosphorylation of 4E-BP1, dissociation of the 4E-BP1-eIF4E complex, and increase in protein synthesis required activation of both PI 3-kinase and ERK pathways. Furthermore, ERK activation by IGF-I was also PI 3-kinase dependent. Transfection with the Thr(37,46)-->Ala(37,46) mutant of 4E-BP1 showed that phosphorylation of Thr(37,46) residues was required for IGF-I induction of protein synthesis in MCT cells. Our observations reveal the importance of initial events in protein translation in IGF-I-induced protein synthesis in MCT cells and identify the regulatory signaling pathways involved. C1 Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med,S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. McGill Univ, Dept Biochem, Montreal, PQ H3Z 2Z3, Canada. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med,S Texas Vet Hlth Care Syst, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu FU NIDDK NIH HHS [DK-55815] NR 54 TC 30 Z9 30 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 DEC PY 2002 VL 283 IS 6 BP F1226 EP F1236 DI 10.1152/ajprenal.00109.2002 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 613AA UT WOS:000179106600007 PM 12388420 ER PT J AU Zharkikh, L Zhu, XH Stricklett, PK Kohan, DE Chipman, G Breton, S Brown, D Nelson, RD AF Zharkikh, L Zhu, XH Stricklett, PK Kohan, DE Chipman, G Breton, S Brown, D Nelson, RD TI Renal principal cell-specific expression of green fluorescent protein in transgenic mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE renal collecting duct; aquaporin-2; gene expression regulation ID VACUOLAR H+-ATPASE; RAT-KIDNEY; INTERCALATED CELLS; COLLECTING DUCT; WATER CHANNEL; MICROTUBULE DISRUPTION; VASOPRESSIN; MOUSE; GENE; AQUAPORIN-2 AB The purpose of this study is to develop transgenic mice with principal cell-specific expression of green fluorescent protein (GFP). After the cloning and sequencing of the mouse aquaporin-2 (AQP2) gene, 9.5 kb of the promoter were used to drive expression of GFP in transgenic mice. In transgenic mice, GFP was selectively expressed in principal cells of the renal collecting duct and not in intercalated cells. Expression was increased by dehydration of mice. AQP2 and GFP expression was maintained in primary cultures of renal medulla that were stimulated with cAMP or vasopressin analogs. GFP-expressing cells were then isolated by fluorescence-activated cell sorting. RT-PCR analysis showed expression of AQP2, AQP3, AQP4, vasopressin type 2 receptor, and cAMP response element binding protein but not H(+)-ATPase B1 subunit or anion exchanger 1. After expansion of these cells in culture, RT-PCR analysis showed continued expression of the same genes. This pattern of gene expression is that of principal cells rather than intercalated cells. This transgenic mouse model can be used in future studies of gene expression during the development, differentiation, and maturation of renal principal cells. C1 Univ Utah, Dept Pediat, Div Nephrol, Salt Lake City, UT 84132 USA. Univ Utah, Dept Med, Salt Lake City, UT 84132 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Nelson, RD (reprint author), Univ Utah, Dept Pediat, Div Nephrol, 50 N Med Dr, Salt Lake City, UT 84132 USA. EM raoul.nelson@hsc.utah.edu FU NIDDK NIH HHS [5-R01-DK-53990, DK-38542] NR 54 TC 15 Z9 16 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 DEC PY 2002 VL 283 IS 6 BP F1351 EP F1364 DI 10.1152/ajprenal.00224.2001 PG 14 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 613AA UT WOS:000179106600018 PM 12426236 ER PT J AU Viguera, AC Cohen, LS Bouffard, S Whitfield, TH Baldessarini, RJ AF Viguera, AC Cohen, LS Bouffard, S Whitfield, TH Baldessarini, RJ TI Reproductive decisions by women with bipolar disorder after prepregnancy psychiatric consultation SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 154th Annual Meeting of the American-Psychiatric-Association CY MAY 05-10, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Psychiat Assoc ID ILLNESS; LITHIUM; RISK AB Objective: This study ascertained family planning decisions by women with bipolar disorder after psychiatric consultation. Method: The authors surveyed 116 women with DSM-IV bipolar disorder after specialized consultation about treatment options and risks regarding pregnancy. Results: Of 70 respondents, 45% had been advised to avoid pregnancy by a health care professional before consultation. After consultation, 63% decided to pursue pregnancy. Conclusions: Women with bipolar disorder often encounter obstacles from health care professionals regarding pregnancy. individualized comprehensive review of risks and benefits of treatment options during specialized preconception consultation can support thoughtful clinical planning. C1 Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. McLean Hosp, Int Consortium Bipolar Disorder Res, Belmont, MA 02178 USA. RP Viguera, AC (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. RI Kothari, Khyati/B-5008-2014 FU NIMH NIH HHS [MH 01609] NR 10 TC 46 Z9 50 U1 0 U2 2 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 DEC PY 2002 VL 159 IS 12 BP 2102 EP 2104 DI 10.1176/appi.ajp.159.12.2102 PG 3 WC Psychiatry SC Psychiatry GA 622YF UT WOS:000179675000026 PM 12450965 ER PT J AU Levine, S Nguyen, T Kaiser, LR Shrager, JB AF Levine, S Nguyen, T Kaiser, LR Shrager, JB TI Evaluating respiratory muscle adaptations - A new approach SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; DIAPHRAGM C1 Univ Penn, Med Ctr, Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Levine, S (reprint author), Univ Penn, Med Ctr, Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 9 TC 5 Z9 6 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2002 VL 166 IS 11 BP 1418 EP 1419 DI 10.1164/rccm.2209001 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 621LT UT WOS:000179590900002 PM 12450930 ER PT J AU Abdulla, C Kalra, MK Saini, S Maher, MM Ahmad, A Halpern, E Silverman, SG AF Abdulla, C Kalra, MK Saini, S Maher, MM Ahmad, A Halpern, E Silverman, SG TI Pseudoenhancement of simulated renal cysts in a phantom using different multidetector CT scanners SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society CY APR-MAY -, 2002 CL ATLANTA, GEORGIA SP Amer Roentgen Ray Soc ID CONTRAST-ENHANCED CT; MASSES; CLASSIFICATION AB OBJECTIVE. We undertook this study to determine whether pseudoenhancement of renal cysts occurs on scans obtained with multidetector CT (MDCT) scanners and whether the effect is influenced by scanning parameters. MATERIALS AND METHODS. A kidney phantom with varying attenuation was created to simulate different levels of renal parenchymal enhancement (150 and 250 H). Two water-filled cylinders simulating renal cysts-one with a 5-mm diameter and one with a 15-mm diameter-were suspended in the "kidney." After validating the pseudoenhancement effect produced in our phantom model with a single-detector helical CT scanner, we investigated the effect with matrix array and adaptive array MDCT scanners using detector configurations of 1.25 and 2.5 mm and beam pitches of 0.75:1.0 and 1.5:1.0 at an effective reconstructed slice thickness of approximately 3 nun. Three sets of experiments were performed at each setting, and mean cyst density was measured. Data were statistically analyzed using the Student's t test and multiple logistic regression analysis when appropriate. RESULTS. Although pseudoenhancement was observed with MDCT scanners, the effect was statistically significant only for scans depicting the smaller cyst at a background renal density of 250 H on the matrix array MDCT. Modulation of scanning parameters did not alter these findings. Pseudoenhancement was significantly higher with the matrix array MDCT scanner than with the adaptive array MDCT scanner (p < 0.05). CONCLUSION. In our phantom model, high levels of renal enhancement produced pseudoenhancement in small renal cysts with different models of MDCT scanners, irrespective of pitch or detector configuration. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 15 TC 34 Z9 37 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2002 VL 179 IS 6 BP 1473 EP 1476 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 618FK UT WOS:000179407900016 PM 12438037 ER PT J AU Lucey, BC Boland, GW Maher, MM Hahn, PF Gervais, DA Mueller, PR AF Lucey, BC Boland, GW Maher, MM Hahn, PF Gervais, DA Mueller, PR TI Percutaneous nonvascular splenic intervention: A 10-year review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review ID NEEDLE ASPIRATION BIOPSY; ABDOMINAL ABSCESSES; CATHETER DRAINAGE; FLUID COLLECTIONS; GUIDED BIOPSY; LESIONS; SPLEEN; ULTRASOUND AB OBJECTIVE. We performed a retrospective review of our experiences with percutaneous splenic interventions to evaluate the safety and usefulness of these procedures. We examined both the success rate and the complication rate. MATERIALS AND METHODS. We used our electronic database to perform a retrospective analysis of patients treated from January 1990 to December 2000. Thirty-nine imaging-guided percutaneous splenic procedures were performed in 38 patients: 27 men and 11. women who ranged in age from 17 to 83 years (mean age, 56.5 years). For 28 procedures, sonographic guidance was used, and for 11, CT guidance was used. Procedures performed included splenic biopsy (n = 24), fluid aspiration (n = 8), and fluid drainage (n = 7). RESULTS. Splenic biopsy was successful in 91% of the procedures; fluid aspiration, in 100%; and fluid drainage, in 86%. The overall complication rate was 10.3%, with three patients requiring emergency splenectomy as a result of massive bleeding after the procedure. Two of these patients had previously unrecognized vascular tumors, and one had concomitant refractory thrombocytopenia. CONCLUSION. This study suggests that splenic biopsy can be performed safely and is of considerable value in diagnosis. Our findings also show that percutaneous catheter drainage of splenic abscesses is successful and that splenectomy should be reserved for failed percutaneous drainage. The complications that occur after procedures on vascular tumors emphasize the importance of requiring normal coagulation parameters before the procedure because the vascular nature of the lesion may be difficult to recognize on imaging before the procedure. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Lucey, BC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. NR 28 TC 51 Z9 56 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2002 VL 179 IS 6 BP 1591 EP 1596 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 618FK UT WOS:000179407900036 PM 12438060 ER PT J AU Kalra, MK Prasad, S Saini, S AF Kalra, MK Prasad, S Saini, S TI Clinical comparison of standard-dose and 50% reduced-dose abdominal CT: Effect of image quality (vol 179, pg 1101, 2002) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Correction C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Kalra, MK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2002 VL 179 IS 6 BP 1645 EP 1645 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 618FK UT WOS:000179407900054 ER PT J AU Awad, SS Fagan, S Abudayyeh, S Karim, N Berger, DH Ayub, K AF Awad, SS Fagan, S Abudayyeh, S Karim, N Berger, DH Ayub, K TI Preoperative evaluation of hepatic lesions for the staging of hepatocellular and metastatic liver carcinoma using endoscopic ultrasonography SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Southwestern-Surgical-Congress CY APR 07-10, 2002 CL CORONADO, CALIFORNIA SP Southwestern Surg Congress DE endoscopic ultrasonography; hepatocellular cancer; metastatic liver carcinoma; fine needle aspiration; staging ID FINE-NEEDLE ASPIRATION; INTRAOPERATIVE ULTRASONOGRAPHY; COMPUTED-TOMOGRAPHY; COLORECTAL-CANCER; SONOGRAPHY; ULTRASOUND; DIAGNOSIS; ANGIOGRAPHY; ACCURACY; TUMORS AB Background: Noninvasive imaging techniques, such as dynamic computed tomography (CT), magnetic resonance imaging band transabdominal ultrasonography are limited in their ability to detect hepatic lesions less than one cm. Intraoperative ultrasonography (IOUS) is currently the most sensitive modality for the detection of small hepatic lesions. However, IOUS is invasive requiring laparoscopy or formal laparotomy. We sought to evaluate the feasibility of using endoscopic ultrasonograhpy (EUS) for the detection and diagnosis of hepatic masses in patients with hepatocellular cancer (HCCA) and metastatic lesions (ML). We hypothesized that EUS could detect small (< 1.0 cm) hepatic lesions undetectable by CT scan and could be used for biopsy of deep-seated hepatic lesions. Methods: Consecutive patients referred for EUS with suspected liver lesions were evaluated between July 2000 and October 2001. All patients underwent EUS using an Olympus (EM30) radial echoendoscope. If liver lesions were confirmed and fine needle aspiration (FNA) was deemed necessary, a linear array scope was used and an FNA performed with a 22-gauge needle. Two passes were made for each lesion. Results: 14 patients underwent evaluation with dynamic CT scans and EUS. In all 14 patients, EUS. successfully identified hepatic lesions ranging in size from 0.3 cm to 14 cm (right lobe: n = 3, left lobe: n = 1, bilobar: n = 8). Moreover, EUS identified new or additional lesions in 28% (4 of 14) of the patients, all less than 0.5 cm in size (HCCA: n = 2, ML n = 2), influencing the clinical management. In 2 of 14 patients EUS identified liver lesions, previously described as suspicious by CT scan, to be hemangiomas. Nine patients underwent EUS-guided FNA of hepatic lesions (deep seated: n = 3, superficial: n = 6). All FNA passes yielded adequate specimens (malignant: n 8, benign: n = 1). Conclusions: Our preliminary experience suggests that EUS is a feasible preoperative staging tool for liver masses suspected to be HCCA or metastatic lesions. EUS can detect small hepatic lesions previously undetected by dynamic CT scans. Furthermore, EUS-guided FNA can confirm additional HCCA liver lesions or liver metastases, in deep-seated locations, upstaging patients and changing clinical management. (C) 2002 Excerpta Medica Inc. All rights reserved. C1 Houston VAMC, Michael E DeBakey Dept Surg, Surg Serv 112, Houston, TX 77030 USA. Baylor Coll Med, Houston VAMC, Dept Med, Div Gastroenterol, Houston, TX 77030 USA. RP Awad, SS (reprint author), Houston VAMC, Michael E DeBakey Dept Surg, Surg Serv 112, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 17 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 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 2002 VL 184 IS 6 BP 601 EP 604 AR PII S0002-9610(02)01092-9 DI 10.1016/S0002-9610(02)01092-9 PG 4 WC Surgery SC Surgery GA 626LL UT WOS:000179873800043 PM 12488184 ER PT J AU Siqueland, L Crits-Christoph, P Gallop, B Gastfriend, D Lis, J Frank, A Griffin, M Blaine, J Luborsky, L AF Siqueland, L Crits-Christoph, P Gallop, B Gastfriend, D Lis, J Frank, A Griffin, M Blaine, J Luborsky, L TI Who starts treatment: Engagement in the NIDA Collaborative Cocaine Treatment Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT Conference on College of Problems in Drug Dependence CY JUN 14, 1998 CL SCOTTSDALE, ARIZONA ID PSYCHOSOCIAL TREATMENTS; NATIONAL-INSTITUTE; DEPENDENCE; RECRUITMENT; PERFORMANCE; ATTRITION; RETENTION; ABUSERS; DROPOUT; TRIALS AB This study addressed the role of demographic variables, severity of drug dependence, and drug-related problems in facilitating or impeding engagement into a research treatment. Patients were tracked through various stages of entry for the research treatment: phone screening, intake, and randomization to treatment. Results suggested that certain demographic factors put patients more at risk for dropping out at intake and randomization. African-American and unemployed patients were less likely to stay in treatment at both stages, with largest differences at intake. Younger patients were less likely to complete both phases, with bigger differences noted at randomization. Patients with more days of cocaine use and patients referred from advertisements were less likely to keep their intake appointments. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. McLean Hosp, Belmont, MA 02178 USA. NIDA, Treatment Res Branch, Bethesda, MD 20892 USA. RP Siqueland, L (reprint author), Univ Penn, Sch Med, 3535 Market St,6th Fl, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [U01-DA07673, U01-DA07085, U01-DA07090, R01 DA012249, U01-DA07663, U01-DA07693, U18 DA007090, K05-DA00168, K02-DA 00326]; NIMH NIH HHS [K02-MH00756, P30-MH-45178] NR 32 TC 13 Z9 13 U1 3 U2 3 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD WIN PY 2002 VL 11 IS 1 BP 10 EP 23 DI 10.1080/10550490252801602 PG 14 WC Substance Abuse SC Substance Abuse GA 524LQ UT WOS:000174015200002 PM 11876580 ER PT J AU Siqueland, L Crits-Christoph, P Gallop, R Barber, JP Griffin, ML Thase, ME Daley, D Frank, A Gastfriend, DR Blaine, J Connolly, MB Gladis, M AF Siqueland, L Crits-Christoph, P Gallop, R Barber, JP Griffin, ML Thase, ME Daley, D Frank, A Gastfriend, DR Blaine, J Connolly, MB Gladis, M TI Retention in psychosocial treatment of cocaine dependence: Predictors and impact on outcome SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SUBSTANCE-ABUSE TREATMENT; CLINICAL-TRIALS; EARLY ATTRITION; PSYCHOTHERAPY; ABSTINENCE; PARTICIPATION; SEVERITY AB This report describes retention in treatment in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (CCTS), a multi-site trial of four psychosocial treatments for 487 cocaine dependent patients. Younger, African-American, and unemployed patients were retained in treatment for fewer days than their counterparts. African-American patients who lived with a partner were retained in treatment for less time than if they lived alone. Higher psychiatric severity kept men in treatment longer but put women at risk for dropping out sooner. Patients who completed the full treatment used drugs less often than patients who dropped out, but outcome did not differ at each month. Patients in the drug counseling condition stayed in treatment for fewer days than patients in psychotherapy, but they were more likely to be abstinent after dropout. Patients with higher psychiatric severity were more at risk continuing to use drugs after dropout. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. McLean Hosp, Belmont, MA 02178 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NIDA, Bethesda, MD 20892 USA. RP Siqueland, L (reprint author), Univ Penn, Sch Med, 3535 Market St,6th Fl, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [U01-DA07663, K05-DA00168, R01 DA012249, U01-DA07085, U01-DA07090, U01-DA07673, U01-DA07693, U18 DA007090, K02-DA 00326]; NIMH NIH HHS [K02-MH00756, P30-MH-45178] NR 43 TC 47 Z9 47 U1 4 U2 6 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD WIN PY 2002 VL 11 IS 1 BP 24 EP 40 DI 10.1080/10550490252801611 PG 17 WC Substance Abuse SC Substance Abuse GA 524LQ UT WOS:000174015200003 PM 11876581 ER PT J AU Wilens, TE Biederman, J Bredin, E Hahesy, AL Abrantes, A Neft, D Millstein, R Spencer, TJ AF Wilens, TE Biederman, J Bredin, E Hahesy, AL Abrantes, A Neft, D Millstein, R Spencer, TJ TI A family study of the high-risk children of opioid- and alcohol-dependent parents SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SUBSTANCE USE DISORDERS; DRUG-USE; EMOTIONAL-PROBLEMS; YOUNG ADULTHOOD; LATE ADOLESCENT; PSYCHOPATHOLOGY; ABUSE; CHILDHOOD; PATTERNS; ADHD AB In this article, the author sought to use a high-risk study design focused on the children of parents with opioid or alcohol use disorders and children of parents with no substance use disorder (SUD) to evaluate the specificity of the risk conferred by the hype of parental SUD. Using structured psychiatric interviews, cognitive assessments, and measures of social, academic, and family functioning, the authors studied 96 families ( 187 parents and 183 children, mean age of 11.6 years). Sixteen families had parental opioid dependence (22 children, 64% male), 14 families had parental alcohol dependence (22 children; 59% male), and 66 families had no SUD (controls; 139 children; 58% male). Fifty-nine percent of children of opioid-dependent parents had at least one major psychopathological condition, compared to 41% of the alcohol group and 28% of the control group (p < 0.01). The children of opioid- and alcohol-dependent parents were of lower socioeconomic status and had significantly more difficulties in academic, social, and family functioning than did controls. Children of opioid- and alcohol-dependent parents have significantly, higher rates of psychopathology as well as more difficulties in academic, social, and family functioning compared to the children of non-SUD parents. In addition, notable trends emerged for the opioid group to have more psychopathology and functional impairment than the alcohol group. With a growing consensus that certain risk factors for later SUD start in childhood with potentially treatable childhood-onset disorders, new preventive approaches for individuals at risk may be developed targeting childhood precursors of SUD. C1 Massachusetts Gen Hosp, ACC 725, Pediat Psychopharmacol Unit, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, ACC 725, Pediat Psychopharmacol Unit, Clin Res Program Pediat Psychopharmacol, 15 Parkman St, Boston, MA 02114 USA. FU NIDA NIH HHS [DA-1192901A, DA-R2911315]; NIMH NIH HHS [MH-K2001175A] NR 70 TC 25 Z9 26 U1 1 U2 5 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD WIN PY 2002 VL 11 IS 1 BP 41 EP 51 DI 10.1080/10550490252801620 PG 11 WC Substance Abuse SC Substance Abuse GA 524LQ UT WOS:000174015200004 PM 11876582 ER PT J AU Arteaga, JR Huerta, S Livingston, EH AF Arteaga, JR Huerta, S Livingston, EH TI Management of gastrojejunal anastomotic leaks after Roux-en-Y gastric bypass SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 18-20, 2002 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surgeons, SO Calif Chapter ID VERTICAL BANDED GASTROPLASTY; MORBID-OBESITY; COMPLICATIONS; SURGERY; TRIAL AB Anastomotic leaks after Roux-en-Y gastric bypass (RYGB) potentially result in considerable morbidity and mortality. In the present report we describe our experience with the management of gastrojejunal anastomotic leaks. Tachycardia and fever are considered early signs of anastomotic disruption. Patients weighing less than 350 pounds underwent radiographic testing to diagnose gastrojejunal disruption. Those with severe leaks or patients too large for radiographic evaluation underwent exploratory laparotomy. For severe anastomotic disruptions a retrograde transanastomotic jejunal sump drain was placed. Twenty-four (1.3%) anastomotic leaks occurred in 1789 RYGBs. Five of the leaks were classified as severe and required retrograde sump tube placement. There was one mortality and all of the other patients completely recovered. Aggressive and early intervention for anastomotic disruption after RYGB is necessary to ensure the best possible outcomes for patients with this complication. A high index of suspicion for leaks in postoperative RYGB patients with tachycardia is required if patients are to have good outcomes when complications develop. C1 Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA 90095 USA. VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA 90095 USA. RP Arteaga, JR (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, 900 Vet Ave,Warren Hall,Room 12-217, Los Angeles, CA 90095 USA. NR 18 TC 22 Z9 22 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD DEC PY 2002 VL 68 IS 12 BP 1061 EP 1065 PG 5 WC Surgery SC Surgery GA 629WE UT WOS:000180074100007 PM 12516809 ER PT J AU Hardiman, O Traynor, BJ Corr, B Frost, E AF Hardiman, O Traynor, BJ Corr, B Frost, E TI Models of care for motor neuron disease: setting standards SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Review DE standard of care; ALS; management of ALS; therapy of ALS; healthcare delivery ID AMYOTROPHIC-LATERAL-SCLEROSIS; QUALITY-OF-LIFE; ALS PATIENTS; VENTILATION; SURVIVAL AB Models of care for people with motor neuron disease (MND) must be designed in a patient-centered format, with an inbuilt flexibility and responsiveness that reflect the evolving nature of the condition. Diagnosis should be made as early as possible. Patients should have early access to centres with specialist knowledge of amyotrophic lateral sclerosis (ALS). Services should be flexible and responsive to the needs of the patient, and operate to best advantage when functioning as a coordinated team that cross-refers internally. Patients with ALS should be empowered to make rational end-of-life decisions based on maximizing quality of life and maintaining dignity. All models of care should be designed to cater for the sudden change from health to chronic illness, and should aim to provide a core of specialties that are patient-oriented, flexible and responsive. Ultimately, models of care should be assessed based on their outcomes. C1 Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Hardiman, O (reprint author), Beaumont Hosp, Dept Neurol, Beaumont Rd, Dublin 9, Ireland. RI Traynor, Bryan/G-5690-2010 NR 31 TC 16 Z9 16 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PD DEC PY 2002 VL 3 IS 4 BP 182 EP 185 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 650RV UT WOS:000181277800002 PM 12710506 ER PT J AU Avery, EG MacGillivray, TE AF Avery, EG MacGillivray, TE TI Arrested paradoxical emboli in transit diagnosed by intraoperative transesophageal echocardiography SO ANESTHESIA AND ANALGESIA LA English DT Article ID COUNCIL; AORTA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Cardiothorac Anesthesia, Clin 3,Dept Anesthesia & Crit Care Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, Boston, MA USA. RP Avery, EG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Cardiothorac Anesthesia, Clin 3,Dept Anesthesia & Crit Care Med, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2002 VL 95 IS 6 BP 1569 EP 1571 DI 10.1213/01.ANE.0000035080.64290.10 PG 3 WC Anesthesiology SC Anesthesiology GA 622KK UT WOS:000179646100017 PM 12456417 ER PT J AU Cooper, JB Gaba, D AF Cooper, JB Gaba, D TI No myth: Anesthesia is a model for addressing patient safety SO ANESTHESIOLOGY LA English DT Editorial Material ID MORTALITY; DEATHS; RISK C1 Partners Healthcare Syst Inc, Biomed Engn, Boston, MA USA. Ctr Med Stimulat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. VA Palo Alto Hlth Care Syst, Patient Safety Ctr Inquiry, Palo Alto, CA USA. Stanford Univ, Stanford, CA 94305 USA. RP Cooper, JB (reprint author), Partners Healthcare Syst Inc, Biomed Engn, Boston, MA USA. NR 13 TC 53 Z9 58 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2002 VL 97 IS 6 BP 1335 EP 1337 DI 10.1097/00000542-200212000-00003 PG 3 WC Anesthesiology SC Anesthesiology GA 621LN UT WOS:000179590500002 PM 12459657 ER PT J AU Schwid, HA Rooke, GA Carline, J Steadman, RH Murray, WB Olympio, M Tarver, S Steckner, K Wetstone, S AF Schwid, HA Rooke, GA Carline, J Steadman, RH Murray, WB Olympio, M Tarver, S Steckner, K Wetstone, S CA Anesthesia Simulator Res Consortiu TI Evaluation of anesthesia residents using mannequin-based simulation - A multiinstitutional study SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Spring Meeting of the Society-for-Eduction-in-Anesthesia CY JUN 03, 2001 CL CLEVELAND, OHIO SP Soc Educ Anesthesia ID CRITICAL INCIDENTS; INTERRATER RELIABILITY; PERFORMANCE; VALIDITY; CONSISTENCY; EXPERIENCE AB Background: Anesthesia simulators can generate reproducible, standardized clinical scenarios for instruction and evaluation purposes. Valid and reliable simulated scenarios and grading systems must be developed to use simulation for evaluation of anesthesia residents. Methods: After obtaining Human Subjects approval at each of the 10 participating institutions, 99 anesthesia residents consented to be videotaped during their management of four simulated scenarios on MedSim or METI mannequin-based anesthesia simulators. Using two different grading forms, two evaluators at each department independently reviewed the videotapes of the subjects from their institution to score the residents' performance. A third evaluator, at an outside institution, reviewed the videotape again. Statistical analysis was performed for construct- and criterion-related validity, internal consistency, interrater reliability, and intersimulator reliability. A single evaluator reviewed all videotapes a fourth time to determine the frequency of certain management errors. Results: Even advanced anesthesia residents nearing completion of their training made numerous management errors; however, construct-related validity of mannequin-based simulator assessment was supported by an overall improvement in simulator scores from CB and CA-1 to CA-2 and CA-3 levels of training. Subjects rated the simulator scenarios as realistic (3.47 out of possible 4), further supporting construct-related validity. Criterion-related validity was supported by moderate correlation of simulator scores with departmental faculty evaluations (0.37-0.41, P < 0.01), ABA written in-training scores (0.44-0.49, P < 0.01), and departmental mock oral board scores (0.44-0.47, P < 0.01). Reliability of the simulator assessment was demonstrated by very good internal consistency (alpha = 0.71-0.76) and excellent interrater reliability (correlation = 0.94-0.96; P < 0.01; kappa = 0.81-0.90). There was no significant difference in METI versus MedSim scores for residents in the same year of training. Conclusions: Numerous management errors were identified in this study of anesthesia residents from 10 institutions. Further attention to these problems may benefit residency training since advanced residents continued to make these errors. Evaluation of anesthesia residents using mannequin-based simulators shows promise, adding a new dimension to current assessment methods. Further improvements are necessary in the simulation scenarios and grading criteria before mannequin-based simulation is used for accreditation purposes. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. RP Schwid, HA (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Rooke, Alec/F-8909-2013 NR 17 TC 106 Z9 111 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2002 VL 97 IS 6 BP 1434 EP 1444 DI 10.1097/00000542-200212000-00015 PG 11 WC Anesthesiology SC Anesthesiology GA 621LN UT WOS:000179590500014 PM 12459669 ER PT J AU Zeitels, SM Franco, RA Hillman, RE Bunting, GW AF Zeitels, SM Franco, RA Hillman, RE Bunting, GW TI Voice and treatment outcome from phonosurgical management of early glottic cancer SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 12-13, 2001 CL PALM DESERT, CALIFORNIA SP Amer Larynglog Assoc DE cancer; dysphonia; fat injection; glottis; hoarseness; laryngoplasty; lipoinjection; phonomicrosurgery; phonosurgery; stroboscopy; thyroplasty; vocal cord; vocal fold; voice ID VOCAL CORD CARCINOMA; LASER-SURGERY; RADIATION-THERAPY; CLINICAL-EXPERIENCE; MICROLARYNGOSCOPIC SURGERY; LARYNGOSCOPIC EXPOSURE; LARYNGEAL CARCINOMAS; QUALITY; T1; RADIOTHERAPY AB Phonosurgical management of early glottic cancer has evolved considerably, but objective vocal outcome data are sparse. A prospective clinical trial was done on 32 patients with unilateral cancer (T1a in 28 and T2a in 4) who underwent ultranarrow-margin resection; 15 had resection superficial to the vocal ligament, and 17 deep to it. The subepithelial infusion technique facilitated selection of these patients for the appropriate procedure. All are cancer-free without radiotherapy or open surgery. Involvement of the anterior commissure (22/32) or the vocal process (15/32) of the arytenoid cartilage did not influence local control. Nine of 17 patients had resection of paraglottic musculature, and all underwent medialization reconstruction by lipoinjection and/or Gore-Tex laryngoplasty. Eight of the 17 had resections deep to the vocal ligament, but without vocalis muscle, and I of the 8 underwent medialization. Posttreatment vocal function measures were obtained for all patients. A clear majority of the patients displayed normal values for average fundamental frequency (72%) during connected speech, and normal noise-to-harmonics ratio (75%) and average glottal airflow (91 %) measures during sustained vowels. Smaller majorities of patients displayed normal values for average sound pressure level (SPL; 59%) during connected speech and for maximum ranges for fundamental frequency (56%) and SPL (59%). Fewer than half of the patients displayed normal values for sustained vowel measures of jitter (45%), shimmer (22%), and maximum phonation time (34%). Almost all patients had elevated subglottal pressures and reduced values for the ratio of SPL to subglottal pressure (vocal efficiency). There were significant improvements in a majority of patients for most vocal function measures after medialization reconstruction. Normal or near-normal conversation-level voices were achieved in most cases, regardless of the disease depth, by utilization of a spectrum of resection and reconstruction options. These favorable results are based on establishing aerodynamic glottal competency and preserving the layered microstructure of noncancerous glottal tissue. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 73 TC 21 Z9 23 U1 2 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 DEC PY 2002 VL 111 IS 12 SU 190 BP 3 EP 20 PN 2 PG 18 WC Otorhinolaryngology SC Otorhinolaryngology GA 627BZ UT WOS:000179909700002 PM 12498379 ER PT J AU Zeitels, SM Hillman, RE Mauri, M Desloge, R Doyle, PB AF Zeitels, SM Hillman, RE Mauri, M Desloge, R Doyle, PB TI Phonomicrosurgery in singers and performing artists: Treatment outcomes, management theories, and future directions SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY MAY 11-12, 2002 CL BOCA RATON, FLORIDA SP Amer Broncho Esophagol Assoc DE dysphonia; ectasia; laryngoscopy; microlaryngoscopy; microsurgery; nodule; phonomicrosurgery; phonosurgery; polyp; singer; varix; vocal cord; vocal fold; voice ID OPTICAL COHERENCE TOMOGRAPHY; VOCAL FOLD; LARYNGOTRACHEAL RECONSTRUCTION; LARYNGOSCOPIC EXPOSURE; VOICE QUALITY; MICROFLAP; BIOMECHANICS; NODULES; POLYPS AB Phonomicrosurgery in performing artists has historically been approached with great trepidation, and vocal outcome data are sparse. The vocal liability of surgically disturbing the superficial lamina propria (SLP) and epithelium must be balanced with the inherent detrimental vocal effect of the lesion(s). A prospective investigation was performed on 185 performing artists who underwent phonomicrosurgical resection of 365 lesions: 201 nodules, 71 polyps, 66 varices and ectasias, 13 cysts, 8 keratotic lesions, 2 granulomas, 2 Reinke's edema, and 2 papillomas. Nearly all patients with SLP lesions reported improvement in their postsurgical vocal function. This subjective result was supported by objective acoustic and aerodynamic measures. All postsurgical objective vocal function measures fell within normal limits, including a few that displayed presurgical abnormalities. However, given the relative insensitivity of standard objective measures to assess higher-level vocal performance-related factors, it is even more noteworthy that 8 of 24 objective measures displayed statistically significant postsurgical improvements in vocal function. Such changes in objective measures mostly reflect overall enhancement in the efficiency of voice production. Phonomicrosurgical resection of vocal fold lesions in performing artists is enjoying an expanding role because of a variety of improvements in diagnostic assessment, surgical instrumentation and techniques, and specialized rehabilitation. Most of these lesions are the result of phonotraurna and arise within the SLP. Successful management depends on prudent patient selection and counseling, ultraprecise technique, and vigorous vocal rehabilitation. Furthermore, an understanding of the vocal function and dysfunction of this high-performance population provides all otolaryngologists who manage laryngeal problems with valuable information that they can extrapolate for use in their practices. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Dept Commun Sci & Disorders, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 63 TC 65 Z9 65 U1 0 U2 3 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 2002 VL 111 IS 12 SU 190 BP 21 EP 40 PN 2 PG 20 WC Otorhinolaryngology SC Otorhinolaryngology GA 627BZ UT WOS:000179909700003 PM 12498380 ER PT J AU Higuchi, M Manna, SK Sasaki, R Aggarwal, BB AF Higuchi, M Manna, SK Sasaki, R Aggarwal, BB TI Regulation of the activation of nuclear factor kappa B by mitochondrial respiratory function: Evidence for the reactive oxygen species-dependent and -independent pathways SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-INDUCED APOPTOSIS; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; CONSTITUTIVE ACTIVATION; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; NADPH-OXIDASE; CYTOCHROME-C; CELLS AB Mitochondrial respiratory function regulates the redox status of cells, which, in turn, can control the activation of transcription factors. However, how mitochondria accomplish this modulation is not completely understood. Using the human myelogenous leukemia cells ML-1a, respiration-deficient clone 19 derived from ML-1a, and reconstituted clones, we demonstrated the role of respiratory function in the activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Constitutive activation of NF-kappaB and AP-1 was observed in clone 19, but not in ML-1a, and the constitutive activation observed in clone 19 was completely inhibited in reconstituted clones that have functional mitochondria. Additionally, tumor necrosis factor (TNF)-induced activation of NF-kappaB and AP-1 observed in ML-1a was greatly reduced in clone 19. These results indicate that mitochondrial respiratory function regulates TNF-induced and constitutive activation of NF-kappaB and AP-1. We investigated the roles of reactive oxygen species in NF-kappaB activation. Generation of superoxide detected by hydroethidine, but not hydrogen peroxide detected by dehydrorhodamine 123, was transiently increased by TNF in both of the cells. The antioxidant, pyrrolidine dithiocarbamate, reduced TNF-induced, but not the constitutive, NF-kappaB activation. These results indicate that the increase in superoxide generation might be involved in TNF-induced, but not in constitutive, NF-kappaB activation. Our results thus demonstrate the involvement of mitochondrial respiratory function in the activation of reactive oxygen species-dependent and -independent pathways for NF-kappaB activation. C1 Baylor Coll Med, Dept Neurol, VA Med Ctr, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Cytokine Res Lab, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Bioimmunotherapy, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA. RP Baylor Coll Med, Dept Neurol, VA Med Ctr, Neurol Svc Bldg 100,Room 2B 114,2002 Holcombe Blv, Houston, TX 77030 USA. EM mhiguchi@bcm.tmc.edu RI Aggarwal, Bharat/G-3388-2013 NR 47 TC 19 Z9 20 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD DEC PY 2002 VL 4 IS 6 BP 945 EP 955 DI 10.1089/152308602762197489 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 629LX UT WOS:000180052100010 PM 12573143 ER PT J AU Yazdanpanah, Y Goldie, SJ Losina, E Weinstein, MC Lebrun, T Paltiel, AD Seage, GR Leblanc, G Ajana, F Kimmel, AD Zhang, H Salamon, R Mouton, Y Freedberg, KA AF Yazdanpanah, Y Goldie, SJ Losina, E Weinstein, MC Lebrun, T Paltiel, AD Seage, GR Leblanc, G Ajana, F Kimmel, AD Zhang, H Salamon, R Mouton, Y Freedberg, KA TI Lifetime cost of HIV care in France during the era of highly active antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Article ID AVIUM COMPLEX INFECTION; PRIMARY PROPHYLAXIS; DRUG-USE; AIDS; ADULTS; DISEASE; HOSPITALIZATIONS; MORBIDITY; MORTALITY; VIRADAPT AB Objective: To estimate the treatment and health care costs of HIV infection or AIDS in France during the era of highly active antiretroviral therapy (HAART). Design: We used a clinical database of HIV-infected patients to calculate the resource use and cost of care for different stages of HIV infection. Costs were incorporated into a computer-based, probabilistic simulation model of the natural history and treatment of HIV infection to estimate the lifetime cost of treating patients with HIV disease. Setting: A northern France HIV clinical cohort. Participants: 1232 HIV-infected patients followed from January 1994 through July 1998. Results: In the absence of an AIDS-defining event, the average total cost of care ranged from 670 euros (1 euro=US $1.19) per person-month in the highest CD4 stratum (>500/mul) to 1060 euros per person-month in the lowest CD4 stratum (less than or equal to50/mul). The mean cost of care was estimated at 3370 euros per person-month during the initial months around the occurrence of an AIDS-defining event; at 1750 euros per person-month during the period spanning from 2 months after the diagnosis of specific AIDS-defining event to 1 month prior to death; and at 13 010 euros per person-month in the final month prior to death. If clinical management of HIV infection began at a CD4 cell count of 378/mul, as in this cohort, the discounted lifetime cost of treating an HIV-infected French patient was estimated at 214000 euros. The undiscounted costs were 309 000 euros over a projected life expectancy of 16.4 years. Conclusion: The cost of HIV disease varies widely depending upon the stage of illness. These estimates of stage-specific and lifetime costs of HIV care will assist health policy planners in assessing the burden of disease in the era of HAART and projecting future resource requirements. C1 Univ Lille, Ctr Hosp Tourcoing, Serv Malad Infect & Voyageur, Fac Med, Lille, France. Labores CNRS U362, Lille, France. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Sch Med, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Minist Emploi & Solidarite, Direct Hospitalisat & Org Soins, Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med,Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Dept Med, Boston, MA 02115 USA. Univ Bordeaux 2, INSERM Unit 330, F-33076 Bordeaux, France. RP Yazdanpanah, Y (reprint author), Univ Lille, Ctr Hosp Tourcoing, Serv Malad Infect & Voyageur, Fac Med, Lille, France. FU NIAID NIH HHS [R01 AI042006, R01-AI42006]; ODCDC CDC HHS [U64/CCU119525, U64/CCU114927] NR 46 TC 33 Z9 35 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD DEC PY 2002 VL 7 IS 4 BP 257 EP 266 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 662VP UT WOS:000181969800005 PM 12553480 ER PT J AU Dienstag, JL AF Dienstag, JL TI Lamivudine: is it first-line therapy? SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on Therapies for Viral Hepatitis CY OCT 29-31, 2002 CL BOSTON, MASSACHUSETTS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD DEC PY 2002 VL 7 IS 4 MA 4 BP L83 EP L83 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 662VP UT WOS:000181969800017 ER PT J AU Moriguchi, H Chung, RT Kobayashi, M Sato, C AF Moriguchi, H Chung, RT Kobayashi, M Sato, C TI Management strategies for liver cirrhosis after resection of HCV-related early hepatocellular carcinoma: a decision analysis SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on Therapies for Viral Hepatitis CY OCT 29-31, 2002 CL BOSTON, MASSACHUSETTS C1 Univ Tokyo, Adv Sci & Technol Res Ctr, Tokyo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hlth Econ Grp, Boston, MA USA. Crecon Res, Boston, MA USA. Tokyo Med & Dent Univ, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD DEC PY 2002 VL 7 IS 4 MA 72 BP L129 EP L130 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 662VP UT WOS:000181969800085 ER PT J AU Willems, B Lau, G Leung, N Schiff, E Trepo, C Wright, T Watkins, K Woessner, M Brosgart, C Bourne, E Tait, D AF Willems, B Lau, G Leung, N Schiff, E Trepo, C Wright, T Watkins, K Woessner, M Brosgart, C Bourne, E Tait, D TI Safety and efficacy of adding adefovir dipivoxil to lamivudine therapy in compensated chronic hepatitis B patients with YMDD variant HBV and a reduced, response to lamivudine: 52 week results SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on Therapies for Viral Hepatitis CY OCT 29-31, 2002 CL BOSTON, MASSACHUSETTS C1 CHU Montreal, Montreal, PQ, Canada. Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. Univ Miami, Ctr Liver Dis, Miami, FL 33152 USA. Hop Hotel Dieu, F-69288 Lyon, France. San Francisco VA Med Ctr, San Francisco, CA USA. GlaxoSmithKline, Greenford, Middx, England. GlaxoSmithKline, Res Triangle Pk, NC USA. Gilead Sci Inc, Foster City, CA 94404 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD DEC PY 2002 VL 7 IS 4 MA 45 BP L111 EP L112 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 662VP UT WOS:000181969800058 ER PT J AU Osipov, V Keating, JT Faul, PN Loda, M Datta, MW AF Osipov, V Keating, JT Faul, PN Loda, M Datta, MW TI Expression of p27 and VHL in renal tumors SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 23-MAR 01, 2002 CL CHICAGO, ILLINOIS SP US & Canadian Acad Pathol DE p27; kidney tumor; VHL; cell cycle ID DEPENDENT KINASE INHIBITOR; ALTERED SUBCELLULAR-LOCALIZATION; PROGNOSTIC-SIGNIFICANCE; REDUCED EXPRESSION; BREAST-CANCER; P27(KIP1); CARCINOMA; PROTEIN; PHOSPHORYLATION; DEGRADATION AB Renal tumors, in particular clear cell renal cell carcinomas, have an unclear prognosis and metastatic potential. Cell cycle regulators play a key role in cellular proliferation and have been implicated in neoplasia. The cell cycle inhibitor p27 has been associated with prognosis in various tumor types. Recently a reported association between p27 and Von Hippel-Lindau (VHL) gene function has also been noted. We have examined p27 and VHL expression by immunohistochemistry in a panel of kidney tumors and have noted specific and unique patterns of p27 expression in various tumor types. In addition, we have analyzed p27 expression in clear cell type renal cell carcinomas and have noted a significant association between decreasing p27 expression and increasing tumor size, suggesting a relation between renal cell proliferation and loss of p27 function. These findings suggest a role for p27 in the development of various types of renal tumors. C1 Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. RP Datta, MW (reprint author), Med Coll Wisconsin, Dept Pathol, 9200 W Wilconsion Ave, Milwaukee, WI 53226 USA. NR 24 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD DEC PY 2002 VL 10 IS 4 BP 344 EP 350 DI 10.1097/00022744-200212000-00010 PG 7 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 624VR UT WOS:000179782800010 PM 12607603 ER PT J AU Izikson, L Sober, AJ Mihm, MC Zembowicz, A AF Izikson, L Sober, AJ Mihm, MC Zembowicz, A TI Prevalence of melanoma clinically resembling seborrheic keratosis - Analysis of 9204 cases SO ARCHIVES OF DERMATOLOGY LA English DT Article ID DIAGNOSTIC-ACCURACY; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; APPROPRIATENESS AB Objective: To estimate the prevalence of melanoma clinically mimicking seborrheic keratosis. Design: Retrospective review of cases submitted for histological examination with a clinical diagnosis of seborrheic keratosis or with a differential diagnosis that included seborrheic keratosis. Setting: A tertiary medical care center-based dermatopathology laboratory serving academic dermatology clinics that have a busy pigmented lesion clinic. Materials and Methods: A total of 9204 consecutive pathology reports containing a diagnosis of seborrheic keratosis; in the clinical information field were identified between the years 1992 and 2001 through a computer database search. Reports with a final histological diagnosis of melanoma were selected for further review and clinicopathological analysis. Main Outcome Measure: Histological diagnosis, which was correlated with the preoperative clinical diagnosis. Results: Melanoma was identified in 61 cases (0.66%) submitted for histological examination with a clinical diagnosis that included seborrheic keratosis. Melanoma was in the clinical differential diagnosis of 31 cases (51%). The remaining lesions had a differential diagnosis of seborrheic keratosis vs melanocytic nevus (17 cases, 28%), basal cell carcinoma (7 cases, 12%), or a squamous proliferation (3 cases, 5%). In 3 cases (5%), seborrheic keratosis was the only clinical diagnosis. All histological types of melanoma were represented. Conclusions: Our results confirm that melanoma can mimic seborrheic keratosis. These data strongly support the current policy of submitting for histological examination all specimens that have been removed from patients. C1 Massachusetts Gen Hosp, Dept Dermatol, Dermatopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zembowicz, A (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Dermatopathol Unit, Warren 820,15 Fruit St, Boston, MA 02114 USA. NR 19 TC 32 Z9 34 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 2002 VL 138 IS 12 BP 1562 EP 1566 DI 10.1001/archderm.138.12.1562 PG 5 WC Dermatology SC Dermatology GA 625EV UT WOS:000179804700004 PM 12472343 ER PT J AU Leonard, S Gault, J Hopkins, J Logel, J Vianzon, R Short, M Drebing, C Berger, R Venn, D Sirota, P Zerbe, G Olincy, A Ross, RG Adler, LE Freedman, R AF Leonard, S Gault, J Hopkins, J Logel, J Vianzon, R Short, M Drebing, C Berger, R Venn, D Sirota, P Zerbe, G Olincy, A Ross, RG Adler, LE Freedman, R TI Association of promoter variants in the alpha 7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MAJOR SUSCEPTIBILITY LOCUS; P50 SUPPRESSION; LINKAGE ANALYSIS; CHROMOSOME-15 LOCUS; SUGGESTIVE EVIDENCE; RELATIVES; PEDIGREES; FAMILIES; SMOKING; REGION AB Background: The alpha7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) has been implicated as a candidate gene for schizophrenia, and for an auditory sensory processing deficit found in the disease, by both genetic linkage at 15q14 and biochemical data. The expression of CHRNA7 is reduced in several brain regions in schizophrenic subjects compared with control subjects. This study presents DNA sequence analysis of the core promoter region for CHRNA7 in schizophrenic and control subjects. Methods: Single-strand conformation polymorphism analysis and DNA sequencing were used for mutation screening of the core promoter in the CHRNA7 gene. The sample included subjects from 166 schizophrenic families and 165 controls. Controls had no evidence of current or past psychosis and had auditory evoked potentials recorded. Results: Multiple polymorphic patterns were identified in the CHRNA7 core promoter in both schizophrenic and control subjects. Functional analysis of polymorphisms indicated that transcription was reduced. The prevalence of functional promoter variants was statistically greater in schizophrenic subjects than in the controls. Presence of an alpha7 promoter polymorphism in controls was associated with failure to inhibit the P50 auditory evoked potential response. Conclusions: Although linkage disequilibrium with other genetic alterations cannot be excluded, the CHRNA7 core promoter variants, found in this study, may contribute to a common pathophysiologic feature of schizophrenia. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. RP Leonard, S (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Campus Box C-268-71,4200 E 9th Ave, Denver, CO 80262 USA. FU NIDA NIH HHS [DA 09457, DA 12231]; NIMH NIH HHS [MH 38321, MH 42212] NR 71 TC 318 Z9 328 U1 5 U2 12 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 DEC PY 2002 VL 59 IS 12 BP 1085 EP 1096 DI 10.1001/archpsyc.59.12.1085 PG 12 WC Psychiatry SC Psychiatry GA 623NW UT WOS:000179710600002 PM 12470124 ER PT J AU Brody, AL Mandelkern, MA London, ED Childress, AR Lee, GS Bota, RG Ho, ML Saxena, S Baxter, LR Madsen, D Jarvik, ME AF Brody, AL Mandelkern, MA London, ED Childress, AR Lee, GS Bota, RG Ho, ML Saxena, S Baxter, LR Madsen, D Jarvik, ME TI Brain metabolic changes during cigarette craving SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 09-14, 2000 CL SAN JUAN, PUERTO RICO SP Amer Coll Neuropsychopharmacol ID POSITRON-EMISSION-TOMOGRAPHY; OBSESSIVE-COMPULSIVE DISORDER; SUSTAINED-RELEASE BUPROPION; ANTERIOR CINGULATE CORTEX; ORBITOFRONTAL CORTEX; FUNCTIONAL-ANATOMY; SMOKING CESSATION; PREFRONTAL CORTEX; NICOTINE PATCH; SOMATOSENSORY AREAS AB Background: In functional brain imaging studies, exposure to cues related to cocaine, opiates, and alcohol in dependent individuals is associated with activation of the anterior cingulate gyrus, amygdala, orbitofrontal cortex, and dorsolateral prefrontal cortex. Craving for these substances positively correlates with activity in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula. The objective of this study was to determine changes in regional cerebral glucose metabolism and correlations between craving and regional metabolism in heavy cigarette smokers exposed to cigarette-related cues. Methods: Twenty heavy smokers (who smoked greater than or equal to20 cigarettes per day) and 20 nonsmoking control subjects underwent 2 fluorine 18-fluorodeoxyglucose positron emission tomography scans 10 days apart in randomized order: one while watching a videotape that presented cigarette-related cues and handling a cigarette, and the other while watching an educational (nature) videotape and handling a neutral object (pen). Results: From the neutral to the cigarette cue scan, heavy smokers had greater increases than nonsmoking controls in relative glucose metabolism in the perigenual anterior cingulate gyrus spanning the midline. Significant positive correlations were found between intensity of craving and metabolism in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula bilaterally. An unexpected positive association was found between craving and metabolism in the right sensorimotor cortex. Conclusions: Brain regions associated with arousal, compulsive repetitive behaviors, sensory integration, and episodic memory are activated during exposure to cigarette-related cues and cigarette craving. These regional brain activations and associations with craving are similar to findings with other addictive substances. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Positron Emiss Tomog Ctr, Los Angeles, CA USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Alabama, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. FU NIDA NIH HHS [R01 DA015059] NR 103 TC 264 Z9 273 U1 6 U2 15 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 DEC PY 2002 VL 59 IS 12 BP 1162 EP 1172 DI 10.1001/archpsyc.59.12.1162 PG 11 WC Psychiatry SC Psychiatry GA 623NW UT WOS:000179710600011 PM 12470133 ER PT J AU Gragoudas, E Li, WJ Goitein, M Lane, AM Munzenrider, JE Egan, KM AF Gragoudas, E Li, WJ Goitein, M Lane, AM Munzenrider, JE Egan, KM TI Evidence-based estimates of outcome in patients irradiated for intraocular melanoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PROTON-BEAM IRRADIATION; NATIONAL DEATH INDEX; PROGNOSTIC SCORING SYSTEM; POSTERIOR UVEAL MELANOMA; COMS RANDOMIZED TRIAL; CHOROIDAL MELANOMA; PLAQUE RADIOTHERAPY; MALIGNANT-MELANOMA; RADIATION MACULOPATHY; CATARACT-EXTRACTION AB Background: Melanoma of the eye is the only potentially fatal ocular malignancy in adults. Until radiation therapy gained wide acceptance in the 1980s, enucleation was the standard treatment for the tumor. Long-term results after proton beam irradiation are now available. Methods: We developed risk score equations to estimate probabilities of the 4 principal treatment outcomes-local tumor recurrence, death from metastasis, retention of the treated eye, and vision loss-based on an analysis of 2069 patients treated with proton beam radiation for intraocular melanoma between July 10, 1975, and December 31, 1997. Median follow-up in surviving patients was 9.4 years. Results: Tumor regrowth occurred in 60 patients, and 95% of tumors (95% confidence interval, 93%-96%) were controlled locally at 15 years. Risk scores were developed for the other 3 outcomes studied. Overall, the treated eye was retained by 84% of patients (95% confidence interval, 80%-87%) at 15 years. The probabilities for vision loss (visual acuity worse than 20/200) ranged from 100% to 20% at 10 years and for death from tumor metastases from 95% to 35% at 15 years, depending on the risk group. Conclusions: High-dose radiation treatment was highly effective in achieving local control of intraocular melanomas. In most cases, the eye was salvaged, and functional vision was retained in many patients. The mortality rate was high in an identifiable subset of patients who may benefit from adjuvant therapies directed at microscopic liver metastases. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts New England Med Ctr, Biostat Res Ctr, Boston, MA USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. RP Gragoudas, E (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 51 TC 95 Z9 97 U1 0 U2 6 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 DEC PY 2002 VL 120 IS 12 BP 1665 EP 1671 PG 7 WC Ophthalmology SC Ophthalmology GA 624AV UT WOS:000179737900007 PM 12470140 ER PT J AU Lee, JB Javier, JA Chang, JH Chen, CC Kato, T Azar, DT AF Lee, JB Javier, JA Chang, JH Chen, CC Kato, T Azar, DT TI Confocal and electron microscopic studies of laser subepithelial keratomileusis (LASEK) in the white leghorn chick eye SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID IN-SITU KERATOMILEUSIS; HUMAN TEAR FLUID; PHOTOREFRACTIVE KERATECTOMY; KERATOCYTE LOSS; CORNEAL DEEPITHELIALIZATION; HIGH MYOPIA; FOLLOW-UP; COMPLICATIONS; MODULATION; APOPTOSIS AB Objectives: To evaluate the effect of 20% alcohol on the white leghorn chick cornea and to determine the confocal and electron microscopic findings of laser subepithelial keratomileusis surgery in the white leghorn chick corneal model. Method: Laser subepithelial keratomileusis surgery was performed on chick corneas and the morphologic changes were examined by transmission electron microscopy. Chick corneas were exposed to 20% alcohol for 30 and 45 seconds or 1 and 2 minutes (5 chicks per group) to evaluate the effect on the corneal epithelium. Photorefractive keratectomy using either mechanical or 20% alcohol-assisted debridement (5 chicks per group) was also performed. Keratocyte and epithelial cell deaths were analyzed 4 hours after surgery using terminal deoxynucleotidyl transfer-mediated biotin-dexoyuridine 5-triphosphate nick-end labeling (TUNEL) staining and transmission electron microscopy. Results: Exposure of the corneal epithelium to 20% alcohol for 30 seconds or longer allowed reproducible separation of epithelial flaps in white leghorn chick eyes. Transmission electron microscopy immediately after alcohol treatment showed that exposure to 20% alcohol for 30 seconds or less had minimal adverse effects on the corneal epithelium. The TUNEL staining of corneas obtained 4 hours after surgery revealed TUNEL-positive cells in the central superficial stroma and more abundantly in the peripheral superficial stroma around the epithelial flap margin and in the epithelial flap itself, particularly in the basal epithelial layer. Transmission electron microscopy showed similar evidence of apoptosis in the epithelium and anterior stroma. Conclusions: The white leghorn chick eye seems to be a reasonable model for laser subepithelial keratomileusis surgery. Treatment with 20% alcohol for 30 seconds results in reproducible epithelial flap creation in the chick cornea and in relatively low levels of stromal and epithelial cell death after surgery. C1 Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 47 TC 32 Z9 33 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2002 VL 120 IS 12 BP 1700 EP 1706 PG 7 WC Ophthalmology SC Ophthalmology GA 624AV UT WOS:000179737900012 PM 12470145 ER PT J AU Colby, K AF Colby, K TI Now we number 33 - Women in ophthalmologhy at Massachusetts Eye and Ear Infirmary in 2002 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ACADEMIC MEDICINE; INSIGHTS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Colby, K (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St,Suite 808, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2002 VL 120 IS 12 BP 1738 EP 1740 PG 3 WC Ophthalmology SC Ophthalmology GA 624AV UT WOS:000179737900018 PM 12470151 ER PT J AU Kratz, A Januzzi, JL Lewandrowski, KB Lee-Lewandrowski, E AF Kratz, A Januzzi, JL Lewandrowski, KB Lee-Lewandrowski, E TI Positive predictive value of a point-of-care testing strategy on first-draw specimens for the emergency department-based detection of acute coronary syndromes SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC TROPONIN-I; CREATINE-KINASE-MB; CHEST PAIN EVALUATION; RISK STRATIFICATION; MYOGLOBIN; TIROFIBAN; ELEVATION; MARKERS; BENEFIT AB Context.-The rapid and accurate diagnosis of the etiology of chest pain is of central importance in the triage of patients presenting to emergency departments. The "first-draw" sensitivity of serum cardiac markers is known to be low on initial presentation; however, less is understood regarding the predictive value of a positive test in this situation. Objective.-To determine the ability of a critical pathway combining medical history and physical examination, electrocardiographic findings, point-of-care testing, and central laboratory data to accurately predict the presence of acute coronary ischemia. Methods.-We investigated the positive predictive value of a testing algorithm for first-draw specimens in clinical practice, combining a qualitative, point-of-care, triplescreen testing panel for cardiac markers, including myoglobin, creatine kinase-MB, and cardiac troponin 1, with confirmation of the rapid assay in the central hospital laboratory by quantitative assays for creatine kinase-MB and cardiac troponin T. Results.-While a positive result on any of the individual cardiac markers of the point-of-care test had a positive predictive value for the acute coronary syndrome of only 36% (creatine kinase-MB, 41%; myoglobin, 36%; and troponin 1, 65%), the positive predictive value for the diagnosis of acute coronary syndrome increased to 76% if all 3 point-of-care markers were simultaneously positive. The positive predictive value for acute coronary syndrome for a positive confirmatory result in the hospital laboratory for either creatine kinase-MB or cardiac troponin T Was 61%. Among those patients with a positive marker on both the point-of-care test and the laboratory test, a careful retrospective review of the clinical history (with exclusion of patients with nonischemic cardiac pathologies and renal insufficiency) increased the positive predictive value of this algorithm to 98%. Conclusions.-Our data suggest that qualitative, point-of-care, triple-screen cardiac marker testing of patients with chest pain at initial presentation may exhibit relatively low positive predictive values. Positive predictive value can be significantly improved by rapid confirmation in the hospital laboratory and careful review of clinical findings. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Labs,Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Lee-Lewandrowski, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Labs,Div Lab Med, 55 Fruit St,GRB 5 Chem, Boston, MA 02114 USA. NR 31 TC 11 Z9 11 U1 1 U2 1 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 DEC PY 2002 VL 126 IS 12 BP 1487 EP 1493 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 626CW UT WOS:000179855600008 PM 12456209 ER PT J AU Boulis, AK Long, J AF Boulis, AK Long, J TI Variation in the treatment of children by primary care physician specialty SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID FAMILY PRACTITIONERS; GENERAL INTERNISTS; OTITIS-MEDIA; PEDIATRICIANS; PATTERNS; OUTCOMES; MEDICINE; SERVICES AB Objective: To investigate specialty differences in the treatment of a diverse array of routine childhood problems. Study Design: Analysis of the first round of the Community Tracking Study Physician Survey, a survey designed to assess the effect of corporatization of medicine on physician practice patterns. Participants: A cohort of 1735 pediatricians and 1267 family practitioners interviewed between 1996 and 1997 for round 1 of the Community Tracking Study. Physicians practicing more than 20 hours per week in the United States, whose primary specialty is either general pediatrics or family practice were included. Main Outcome Measure: Physicians' responses to 6 vignettes describing model patients with clinical presentations contrived to have multiple appropriate treatment plans. Results: Relative to general pediatricians, family practitioners are more likely to: (1) recommend desmopressin acetate for primary enuresis (58.9% vs 37.4%); (2) request an office visit for a child with nasal stuffiness, fever, and no other symptoms (69.8% vs 63.3%); (3) recommend a chest x-ray for a child with productive cough, tachypnea, and rales at the right base (51.3% vs 47.7%); (4) refer a 4-year-old child with eczema and seasonal asthma to an allergist (64.3% vs; 59.2%,); and (5) refer a child with recurring suppurative otitis media to an otolaryngologist (49.7% vs; 33.9%). However, family practitioners are significantly less likely than pediatricians to order a sepsis workup on a 6-week-old infant with a temperature of 38.3degreesC (66.4% vs 81.1%). Physician attributes, practice characteristics, referral patterns, and geographical traits explain little of these differences in practice style. Conclusions: On average, there are significant differences between the approaches of pediatricians and family practitioners to the treatment of children, which may relate to the relative experience that each profession has in treating children. C1 Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Boulis, AK (reprint author), Univ Penn, Dept Sociol, 3718 Locust Walk, Philadelphia, PA 19104 USA. NR 34 TC 8 Z9 10 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD DEC PY 2002 VL 156 IS 12 BP 1210 EP 1215 PG 6 WC Pediatrics SC Pediatrics GA 622RU UT WOS:000179661400011 PM 12444832 ER PT J AU Doyle, PJ AF Doyle, PJ TI Measuring health outcomes in stroke survivors SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE health status; rehabilitation; stroke ID QUALITY-OF-LIFE; VALIDITY; TRIALS; SCALE AB Stroke frequently results in psychologic distress and activity limitations across multiple domains of functioning. However, most stroke outcome measurement tools and clinical trial endpoints are narrowly focused on neurologic symptom status and physical aspects of functioning, and rarely assess other important components of health. In this article, I discuss the limitations in the measurement of nonfatal stroke outcomes; propose a minimum set of fundamental assessment domains comprising a comprehensive assessment of health status in stroke survivors; and describe the conceptual development of the Burden of Stroke Scale, a comprehensive, patient-reported measure of functioning and well-being for stroke survivors. C1 VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. RP Doyle, PJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, 132A-H,7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 36 TC 35 Z9 37 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2002 VL 83 IS 12 SU 2 BP S39 EP S43 DI 10.1053/apmr.2002.36838 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 624CR UT WOS:000179743200006 PM 12474170 ER PT J AU Fu, YC Luo, NL Lopes-Virella, MF Garvey, WT AF Fu, YC Luo, NL Lopes-Virella, MF Garvey, WT TI The adipocyte lipid binding protein (ALBP/aP2) gene facilitates foam cell formation in human THP-1 macrophages SO ATHEROSCLEROSIS LA English DT Article DE lipid binding protein; oxLDL; macrophage; foam cell; atherosclerosis ID LOW-DENSITY-LIPOPROTEIN; FATTY-ACID-BINDING; PPAR-GAMMA; OXIDIZED LDL; SIGNALING PATHWAY; EXPRESSION; ATHEROSCLEROSIS; DIFFERENTIATION; OXIDATION; AP2 AB The critical initiating event in atherogenesis involves the invasion of monocytes through the endothelial wall of arteries, and their transformation from macrophages into foam cells. Human THP-1 monocytic cells can be induced to differentiate into macrophages by phorbol myristate acetate (PMA) treatment, and can then be converted into foam cells by exposure to oxidized low-density lipoprotein (oxLDL). To define genes that are specifically expressed during the transformation of macrophages into foam cells, we have performed a subtractive library screening utilizing mRNA isolated from THP-1 macrophages and foam cells. From this analysis, we have identified adipocyte lipid binding protein (ALBP/aP2) as a gene that is highly upregulated in foam cells in response to oxLDL. Furthermore, overexpression the ALBP gene using an adenovirus construct enhanced the accumulation of cholesterol ester in macrophage foam cells, probably due to an increase in transcription since oxLDL enhanced ALBP promoter activity in experiments using a promoter-luciferase reporter gene construct. The induction of ALBP by oxLDL probably involved activation of peroxisome proliferator-activated receptor gamma (PPARgamma) transcription factors, since four different endogenous PPARgamma ligands, including 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE), two oxidized lipid components of oxLDL, as well as 15-deoxy-delta 12,14 prostaglandin J2 (15d-PGJ2) and retinoic acid (RA), all induced ALBP expression in macrophage/foam cells. Finally, ALBP was found to be highly expressed in vivo in macrophage/foam cells of human atherosclerotic plaques. These observations suggest that oxLDL-mediated increase in ALBP gene expression accelerate cholesterol ester accumulation, and that this is an important component of the genetic program regulating conversion of macrophages to foam cells. The observation that ALBP is readily detected in foam cells in active atherosclerotic lesions implicates a role for ALBP in human vascular disease. The induction of ALPB expression by oxLDL likely involves activation of PPARgamma by components of oxLDL (9-HODE and 13-HODE) that also function as PPARgamma ligands. Our results add to the concern that the clinical use of insulin-sensitizing PPARgamma agonists (i.e. thiazolidinediones) to treat Type 2 Diabetes could exacerbate atherosclerosis, and highlight the need for clinical trials that address this issue. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29401 USA. RP Fu, YC (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, STB-514,114 Doughty St, Charleston, SC 29403 USA. FU NCRR NIH HHS [P20 RR16434]; NHLBI NIH HHS [P01-HL55782]; NIDDK NIH HHS [DK38764] NR 39 TC 96 Z9 110 U1 2 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2002 VL 165 IS 2 BP 259 EP 269 AR PII S0021-9150(02)00305-2 DI 10.1016/S0021-9150(02)00305-2 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 617FR UT WOS:000179351700009 PM 12417276 ER PT J AU Batten, SV Follette, VM Hall, MLR Palm, KM AF Batten, SV Follette, VM Hall, MLR Palm, KM TI Physical and psychological effects of written disclosure among sexual abuse survivors SO BEHAVIOR THERAPY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; EMOTIONAL DISCLOSURE; RHEUMATOID-ARTHRITIS; PSYCHOTHERAPY; VICTIMIZATION; EXPERIENCES; WOMEN AB Although numerous studies demonstrate the efficacy of writing about stressful events on measures of participants' health, most studies have included psychologically and physically healthy participants. The purpose of the current study was to determine whether writing about stressful or traumatic events would have the same effect with participants who had experienced a significant trauma. The physical and psychological impact of writing about child sexual abuse (CSA) experiences or time management was examined in 61 women (mean age 35.0) who reported a CSA history. Participants completed biweekly telephone interviews for 12 weeks after writing, as well as 12-week follow-up questionnaires. The results indicate that writing about CSA history alone is not sufficient to provide psychological or physical health benefits. As these results diverge from the extant literature, possible reasons for these findings are discussed, along with implications for writing interventions with survivors of significant traumas. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Univ Nevada, Reno, NV 89557 USA. RP Batten, SV (reprint author), Yale Univ, POB 208091, New Haven, CT 06510 USA. NR 42 TC 55 Z9 55 U1 1 U2 6 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD WIN PY 2002 VL 33 IS 1 BP 107 EP 122 DI 10.1016/S0005-7894(02)80008-9 PG 16 WC Psychology, Clinical SC Psychology GA 533KT UT WOS:000174529300007 ER PT J AU Podolsky, DK AF Podolsky, DK TI The current future understanding of inflammatory bowel disease SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article DE innate and adaptive immunity; commensal bacteria; cytokines; genes; leukocyte recruitment; restitution; Nod/CARD ID PLACEBO-CONTROLLED TRIAL; ACTIVE CROHNS-DISEASE; NECROSIS-FACTOR-ALPHA; ULCERATIVE-COLITIS; DOUBLE-BLIND; MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI; SUSCEPTIBILITY; INFLIXIMAB; SMOKING AB Accumulating evidence indicates that the inflammatory bowel diseases result from an activation of immune and inflammatory responses initiated by a stimulation of the luminal flora or their products. Genetically determined variations in key mucosal functions, including cell activation by prototypic bacterial pattern molecules, lead to differential susceptibility to the development of these disorders, probably reflecting an interrelated activation of the innate and adaptive immune responses. The persistence and amplification of inflammation is likely to reflect the continuing presence of the driving stimulus and the complex, self-reinforcing activation of select T-helper subtypes and macrophages and other antigen-presenting cells, mediated by several cytokines. The latter include interleukins-2, 12, and 18 as well as interferon and macrophage migration inhibitory factors. The production of other broadly pro-inflammatory cytokines, most notably tumour necrosis factor and interleukins-1 and 6, enhances related inflammatory processes that eventually lead to many of the clinical manifestations of inflammatory bowel disease. The overall severity of the inflammatory process reflects a balance between leukocyte recruitment and downregulatory mucosal repair processes. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. FU NIDDK NIH HHS [P30 DK43351-11] NR 36 TC 68 Z9 68 U1 2 U2 7 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6918 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD DEC PY 2002 VL 16 IS 6 BP 933 EP 943 DI 10.1053/bega.2002.0354 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 629NW UT WOS:000180056600008 PM 12473299 ER PT J AU Tikkanen, R Icking, A Beicht, P Waneck, GL Herzog, V AF Tikkanen, R Icking, A Beicht, P Waneck, GL Herzog, V TI The receptor-bound N-terminal ectodomain of the amyloid precursor protein is associated with membrane rafts SO BIOLOGICAL CHEMISTRY LA English DT Article DE Alzheimer's disease; detergent-resistant membranes; growth factor; microdomain ID GROWTH-FACTOR RECEPTOR; GPI-ANCHORED PROTEINS; LOW-BUOYANT DENSITY; ALZHEIMERS-DISEASE; LIPID RAFTS; CAVEOLAE MEMBRANE; PLASMA-MEMBRANE; CELL-SURFACE; IN-VIVO; DOMAIN AB The soluble N-terminal ectodomain of amyloid precursor protein (sAPP), resulting from alpha-secretase-mediated proteolytic processing, has been shown to function as a growth factor for epithelial cells, including keratinocytes and thyrocytes. Extracellularly applied sAPP binds to a cell surface receptor and exhibits a patchy binding pattern reminiscent of that observed for raft proteins. Here we show that (i) the receptor-bound sAPP resides in a detergent-insoluble membrane microdomain which cofractionates in density gradients with cholesterol-rich membrane rafts and caveolae; (ii) the sAPP-binding microdomains are different from caveolae; and (iii) sAPP is capable of binding to isolated rafts and inducing tyrosine phosphorylation of some raft proteins. These observations suggest that a novel type of membrane raft is involved in sAPP signaling. C1 Univ Bonn, Inst Cell Biol, D-53121 Bonn, Germany. Univ Bonn, Bonner Forum Biomed, D-53121 Bonn, Germany. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Tikkanen, R (reprint author), Univ Bonn, Inst Cell Biol, Ulrich Haberland Str 61A, D-53121 Bonn, Germany. NR 50 TC 8 Z9 8 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD DEC PY 2002 VL 383 IS 12 BP 1855 EP 1864 DI 10.1515/BC.2002.209 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 623YF UT WOS:000179731700004 PM 12553722 ER PT J AU von Knoch, M von Knoch, F AF von Knoch, M von Knoch, F TI Cleaning the surface of cemented orthopedic implants without compromising surface characteristics SO BIOMEDIZINISCHE TECHNIK LA German DT Article DE orthopedics; cemented implants; cleaning procedure; surface ID HIP PROSTHESES AB Prior to the analysis of explanted cemented orthopedic implants, complete removal of foreign material, blood and residual tissue and thorough cleaning of the surface without compromising its characteristics is essential. We describe a reprocessing procedure comprising the following 4 steps: 1) retrieval and storage, 2) removal of residual bone cement, 3) chemical cleaning in an enzymatic solution, and 4) mechanical cleaning in an ultrasound bath. C1 Univ Essen Gesamthsch, Orthopad Klin & Poliklin, Essen, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biomat Lab, Boston, MA USA. RP von Knoch, M (reprint author), Buetteler Weg 22, D-27607 Langen, Germany. NR 11 TC 0 Z9 0 U1 0 U2 1 PU FACHVERLAG SCHIELE SCHON PI BERLIN PA MARKGRAFENSTRASSE 11, D-10969 BERLIN, GERMANY SN 0013-5585 J9 BIOMED TECH JI Biomed. Tech. PD DEC PY 2002 VL 47 IS 12 BP 315 EP 316 PG 2 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 633UH UT WOS:000180300500003 PM 12585049 ER PT J AU Huang, J Harrington, D AF Huang, J Harrington, D TI Penalized partial likelihood regression for right-censored data with bootstrap selection of the penalty parameter SO BIOMETRICS LA English DT Article DE cross-validation; model-based bootstrap; penalized partial likelihood; penalty parameter; proportional hazards model ID MULTIPLE-MYELOMA; CROSS-VALIDATION; VARIABLE SELECTION; SURVIVAL ANALYSIS; RIDGE REGRESSION; COX REGRESSION; CLINICAL-TRIAL; PREDICTION; SHRINKAGE; MODEL AB The Cox proportional hazards model is often used for estimating the association between covariates and a potentially censored failure time, and the corresponding partial likelihood estimators are used for the estimation and prediction of relative risk of failure. However, partial likelihood estimators are unstable and have large variance when collinearity exists among the explanatory variables or when the number of failures is not much greater than the number of covariates of interest. A penalized (log) partial likelihood is proposed to give more accurate relative risk estimators. We show that asymptotically there always exists a penalty parameter for the penalized partial likelihood that reduces mean squared estimation error for log relative risk, and we propose a resampling method to choose the penalty parameter. Simulations and an example show that the bootstrap-selected penalized partial likelihood estimators can, in some instances, have smaller bias than the partial likelihood estimators and have smaller mean squared estimation and prediction errors of log relative risk. These methods are illustrated with a data set in multiple myeloma from the Eastern Cooperative Oncology Group. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Huang, J (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA39929]; NIAID NIH HHS [AI24643] NR 29 TC 18 Z9 18 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2002 VL 58 IS 4 BP 781 EP 791 DI 10.1111/j.0006-341X.2002.00781.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 620NL UT WOS:000179539400009 PM 12495132 ER PT J AU Choi, SW Elmaleh, DR Hanson, RN Shoup, TM Fischman, AJ AF Choi, SW Elmaleh, DR Hanson, RN Shoup, TM Fischman, AJ TI Novel (bisarylmethoxy)butylpiperidine analogues as neurotransmitter transporter inhibitors with activity at dopamine receptor sites SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID COCAINE-ABUSE; 1-<2-ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES GBR-12935; REUPTAKE INHIBITORS; SQUIRREL-MONKEYS; HIGH-AFFINITY; BEHAVIOR; 1-<2-(DIPHENYLMETHOXY)ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES; SEROTONIN; GBR12909; BINDING AB A series of (bisarylmethoxy)butylpiperidine derivatives was prepared and evaluated in vitro and in vivo to determine the structural requirements necessary for dual activity at the DAT and DA/5-HT receptor sites, These hybrid ligands, constructed by combining pharmacophores specific for the DAT and DA/5-HT receptors, could be useful drugs for treating cocaine addiction by assisting cocaine addicts in maintaining abstinence. The series was evaluated in vitro for DAT and DA/5-HT receptor activity and then selected compounds were tested in vivo for their effects on cocaine-induced hyperlocomotor activity (LMA). The majority of the new compounds demonstrated high to moderate affinity (4-191 nM) for the DAT with 4-hydroxy-4-phenylpiperidine analogues 14 and 15 possessing the greatest affinity. Compounds 15 and 22 exhibited the highest ratio of reuptake inhibition-to-binding (discrimination ratio, DR), 111 and 323, respectively. These derivatives had modest affinity and antagonistic activity for dopamine D-2/D-3 receptors. Compounds 9 and 15 (DR = 0.9 and 111. respectively) stimulated locomotor activity, whereas the other compounds suppressed this response, All compounds tested except for 17 and 21 attenuated cocaine-induced hyperlocomotion. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Northeastern Univ, Dept Chem, Boston, MA 02115 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. NR 48 TC 5 Z9 5 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC PY 2002 VL 10 IS 12 BP 4091 EP 4102 AR PII S0968-0896(02)00348-6 DI 10.1016/S0968-0896(02)00348-6 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 618NR UT WOS:000179424600038 PM 12413863 ER PT J AU Damelin, M Silver, PA AF Damelin, M Silver, PA TI In situ analysis of spatial relationships between proteins of the nuclear pore complex SO BIOPHYSICAL JOURNAL LA English DT Article ID RESONANCE ENERGY-TRANSFER; GREEN FLUORESCENT PROTEIN; MESSENGER-RNA EXPORT; NUCLEOCYTOPLASMIC TRANSPORT; NUCLEOPORIN COMPLEX; MOLECULAR ARCHITECTURE; NSP1P; LOCALIZATION; MICROSCOPY; CALMODULIN AB Macromolecular transport between the nucleus and cytoplasm occurs through the nuclear pore complexes (NPCs). The NPC in the budding yeast Saccharomyces cerevisiae is a 60-MDa structure embedded in the nuclear envelope and composed of similar to30 proteins, termed nucleoporins or nups. Here we present a large-scale analysis of spatial relationships between nucleoporins using fluorescence resonance energy transfer (FRET) in living yeast cells. Energy transfer was measured in a panel of strains, each of which coexpresses the enhanced cyan and yellow fluorescent proteins as fusions to distinct nucleoporins. With this approach, we have determined 13 nucleoporin pairs yielding FRET signals. Independent experiments are consistent with the FRET results: Nup120 localization is perturbed in the nic96-1 mutant, as is Nup82 localization in the nup116Delta mutant. To better understand the spatial relationship represented by an in vivo FRET signal, we have investigated the requirements of these signals. We demonstrate that in one case FRET signal is lost upon insertion of a short spacer between the nucleoporin and its enhanced yellow fluorescent protein label. We also show that the Nup120 FRET signals depend on whether the fluorescent moiety is fused to the N- or C-terminus of Nup120. Combined with existing data on NPC structure, the FRET pairs identified in this study allow us to propose a refined molecular model of the NPC. We suggest that the approach may serve as a prototype for the in situ study of other large macromolecular complexes. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 1 Jimmy Fund Way, Boston, MA 02115 USA. NR 59 TC 19 Z9 20 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2002 VL 83 IS 6 BP 3626 EP 3636 PG 11 WC Biophysics SC Biophysics GA 633AD UT WOS:000180256300066 PM 12496130 ER PT J AU Bi, WL Keller-McGandy, C Standaert, DG Augood, SJ AF Bi, WL Keller-McGandy, C Standaert, DG Augood, SJ TI Identification of nitric oxide synthase neurons for laser capture microdissection and mRNA quantification SO BIOTECHNIQUES LA English DT Article ID SOMATOSTATIN-NEUROPEPTIDE-Y; HUNTINGTONS-DISEASE; MESSENGER-RNA; GENE-EXPRESSION; STRIATAL NEURONS; EXCITOTOXIN LESIONS; NMDA RECEPTOR; CELL PICKING; PROJECTION; TISSUE AB An immunohistochemical technique was developed to visualize nitric oxide synthase (NOS)-immunopositive neurons in fresh-frozen tissue sections of rat brain for laser capture microdissection (LCM) and mRNA analysis. The effect of tissue fixation and the choice of fluorophore were investigated. Here we describe a rapid immunofluorescence protocol that allows the processing of fresh-frozen tissue sections within eight minutes and subsequent mRNA extraction and real-time PCR from pools of 20 NOS-immunopositive LCM neurons. The cellular complement of a subset of ionotropic glutamate receptors, specifically N-methyl-D-aspartate receptor subunit mRNAs, was examined because these receptor complexes are thought to mediate the effects of fast and slow glutamate excitotoxicity. Real-time PCR data revealed that striatal NOS interneurons express the mRNAs encoding NR1, NR2A, NR2B, and NR2D but not NR2C. These LCM mRAA data are consistent with previous in situ hybridization studies and demonstrate the utility of rapid immuno-LCM with real-time quantitative PCR for the study of mRNA abundance in discrete populations of neurons within the mammalian brain. C1 Massachusetts Gen Hosp, Dept Neurol, Ctr Aging Genet & Neurodegenerat, Charlestown, MA USA. RP Augood, SJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Aging Genet & Neurodegenerat, 114 16th St, Charlestown, MA USA. OI Standaert, David/0000-0003-2921-8348 NR 45 TC 18 Z9 19 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 2002 VL 33 IS 6 BP 1274 EP + PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 628LL UT WOS:000179996500017 PM 12503312 ER PT J AU Burstein, HJ Parker, LM Savoie, J Younger, J Kuter, I Ryan, PD Garber, JE Campos, SM Shulman, LN Harris, LN Gelman, R Winer, EP AF Burstein, HJ Parker, LM Savoie, J Younger, J Kuter, I Ryan, PD Garber, JE Campos, SM Shulman, LN Harris, LN Gelman, R Winer, EP TI Phase II trial of the anti-VEGF antibody bevacizumab in combination with vinorelbine for refractory advanced breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 28 Z9 28 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 446 BP S115 EP S115 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100343 ER PT J AU Deegan, NI Carsten, CJ Dorman, JP Bovio, SG Thomas, CR AF Deegan, NI Carsten, CJ Dorman, JP Bovio, SG Thomas, CR TI Cancer care providers appropriately offer breast conservation therapy (BCT): pilot data from the South Texas Veterans Health Care System (STVHCS). SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 456 BP S117 EP S117 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100352 ER PT J AU Garber, JE Costantino, JP Wickerham, DL Berliner, N Wolmark, N AF Garber, JE Costantino, JP Wickerham, DL Berliner, N Wolmark, N TI Factor V Leiden (FVL) and prothrombin G20210A (PTG) mutations and risk of thromboembolic events (TE) in NSABP P-1, the breast cancer prevention trial (BCPT). SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Allegheny Gen Hosp, Pittsburgh, PA USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 413 BP S107 EP S107 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100310 ER PT J AU Harris, L Ngo, T Roberts, L Friedman, P Keller, J Fournier, M Iglehart, JD Kuter, I Taghian, A AF Harris, L Ngo, T Roberts, L Friedman, P Keller, J Fournier, M Iglehart, JD Kuter, I Taghian, A TI Detection and monitoring of circulating tumor cells (CTCs) by CK19 mRNA expression in stage II/III breast cancer patients treated on a prospective, randomized clinical trial of sequential neoadjuvant chemotherapy. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 214 BP S63 EP S63 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100139 ER PT J AU Sparano, JA Bernardo, P Gradishar, WJ Ingle, JN Zucker, S Davidson, NE AF Sparano, JA Bernardo, P Gradishar, WJ Ingle, JN Zucker, S Davidson, NE TI Higher trough marimastat levels are associated with accelerated disease progression and worse survival: results of a randomized phase III trial comparing marimastat with placebo in metastatic breast cancer (MBC) after first-line chemotherapy: an Eastern Cooperative Oncology Group trial (E2196). SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Montefiore Med Ctr, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Mayo Clin, Rochester, MN USA. Northport VA Hosp, Northport, NY USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 343 BP S92 EP S92 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100254 ER PT J AU Winer, E Cobleigh, M Dickler, M Miller, K Fehrenbacher, L Jones, C Justice, R AF Winer, E Cobleigh, M Dickler, M Miller, K Fehrenbacher, L Jones, C Justice, R TI Phase II multicenter study to evaluate the efficacy and safety of Tarceva (TM) (erlotinib, OSI-774) in women with previously treated locally advanced or metastatic breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Rush Presbyterian St Lukes Med Ctr, Rush Canc Inst, Chicago, IL 60612 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Kaiser Permanente Med Ctr, Vallejo, CA 94589 USA. Genentech Inc, Med Affairs, San Francisco, CA 94080 USA. NR 0 TC 29 Z9 29 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 445 BP S115 EP S115 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100341 ER PT J AU Mifflin, J AF Mifflin, J TI Tarnished idol: William Thomas Green Morton and the introduction surgical anesthesia: A chronicle of the ether controversy. SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD WIN PY 2002 VL 76 IS 4 BP 831 EP 832 DI 10.1353/bhm.2002.0193 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 618ND UT WOS:000179423400027 ER PT J AU Graham, JS Schomacker, KT Glatter, RD Briscoe, CM Braue, EH Squibb, KS AF Graham, JS Schomacker, KT Glatter, RD Briscoe, CM Braue, EH Squibb, KS TI Efficacy of laser debridement with autologous split-thickness skin grafting in promoting improved healing of deep cutaneous sulfur mustard burns SO BURNS LA English DT Article DE sulfur mustard; laser debridement; skin grafting; wound contraction; image analysis ID PULSED CO2-LASER; CHEMICAL WARFARE; THERMAL-DAMAGE; ABLATION; TISSUE; INJURIES; LESIONS; MODEL AB The consequences of receiving a cutaneous sulfur mustard (SM) burn are prolonged wound healing and secondary infection. This study was undertaken to find a treatment that promotes quick healing with few complications and minimal disfigurement. Multiple deep SM burns (4 cm diameter) were generated on the ventrum of weanling pigs and treated at 48 h. Four treatments were compared: (1) full-thickness CO2 laser debridement followed by skin grafting; (2) full-thickness sharp surgical tangential excision followed by skin grafting, the "Gold Standard" used in deep thermal burns management; (3) partial-thickness laser ablation with no grafting; and (4) partial-thickness sharp excision with no grafting. A computer controlled, raster scanned, high-powered continuous wave (cw) CO2 laser was utilized. Ulceration, wound geometry, and wound contraction were evaluated during a 36-day healing period. Histopathological evaluations were conducted at the end of the healing period. Engraftment rates were similar between both methods of debridement. Laser debridement followed by skin grafting was as efficacious in improving the wound healing of deep SM burns as the "Gold Standard." Full-thickness laser debridement of these small total body surface area (TBSA) burns was time efficient and provided adequate beds for split-thickness skin grafting. Laser debridement offered additional benefits that included hemostatic control during surgery and minimal debridement of normal perilesional skin. Mid-dermal debridement by sharp excision or laser ablation without grafting produced less desirable results but was better than no treatment. Published by Elsevier Science Ltd and ISBI. C1 USA, Med Res Inst Chem Def, Comparat Pathol Branch, Div Comparat Med, Aberdeen Proving Ground, MD 21010 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. USA, Med Res Inst Chem Def, Adv Assessment Branch, Drug Assessment Div, Aberdeen Proving Ground, MD 21010 USA. Univ Maryland, Div Environm Epidemiol & Toxicol, Dept Epidemiol & Preventat Med, Baltimore, MD 21201 USA. RP Graham, JS (reprint author), USA, Med Res Inst Chem Def, Comparat Pathol Branch, Div Comparat Med, 3100 Ricketts Point Rd, Aberdeen Proving Ground, MD 21010 USA. NR 46 TC 29 Z9 30 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD DEC PY 2002 VL 28 IS 8 BP 719 EP 730 AR PII S0305-4179(02)00198-5 DI 10.1016/S0305-4179(02)00198-5 PG 12 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 630ZN UT WOS:000180141900002 PM 12464469 ER PT J AU McGee, G Spanogle, JP Caplan, AL Penny, D Asch, DA AF McGee, G Spanogle, JP Caplan, AL Penny, D Asch, DA TI Successes and failures of hospital ethics committees: A national survey of ethics committee chairs SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article ID MAIL SURVEYS; CONSULTATION C1 Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Columbia Univ, New York, NY USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP McGee, G (reprint author), Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. NR 14 TC 12 Z9 12 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD WIN PY 2002 VL 11 IS 1 BP 87 EP 93 DI 10.1017/S0963180102001147 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA 512ZP UT WOS:000173353700012 PM 11868423 ER PT J AU Gentleman, R Vandal, AC AF Gentleman, R Vandal, AC TI Nonparametric estimation of the bivariate CDF for arbitrarily censored data SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE censored data; clique graph; interval censoring; maximal cliques; nonparametric likelihood ID MAXIMUM-LIKELIHOOD ESTIMATOR; SURVIVOR FUNCTION; ALGORITHM; COMPUTATION; AIDS AB Right, left or interval censored multivariate data can be represented by an intersection graph. Focussing on the bivariate case, the authors relate the structure of such an intersection graph to the support of the nonparametric maximum likelihood estimate (NPMLE) of the cumulative distribution function (CDF) for such data. They distinguish two types of non-uniqueness of the NPMLE: representational, arising when the likelihood is unaffected by the distribution of the estimated probability mass within regions, and mixture, arising when the masses themselves are not unique. The authors provide a brief overview of estimation techniques and examine three data sets. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Gentleman, R (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. NR 24 TC 30 Z9 30 U1 0 U2 2 PU CANADIAN JOURNAL STATISTICS PI OTTAWA PA 675 DENBURY AVENUE, OTTAWA, ON K2A 2P2, CANADA SN 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD DEC PY 2002 VL 30 IS 4 BP 557 EP 571 DI 10.2307/3316096 PG 15 WC Statistics & Probability SC Mathematics GA 661PH UT WOS:000181898600002 ER PT J AU Earle, CC Maroun, J Zuraw, L AF Earle, CC Maroun, J Zuraw, L CA Canc Care Ontario Practice Guideli TI Neoadjuvant or adjuvant therapy for resectable gastric cancer? A practice guideline SO CANADIAN JOURNAL OF SURGERY LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; CARBON-ADSORBED MITOMYCIN; CURATIVE RESECTION; ONCOLOGY-GROUP; INTRAPERITONEAL CHEMOTHERAPY; PERITONEAL RECURRENCE; SURGICAL ONCOLOGY; PLUS TEGAFUR; NO TREATMENT; FOLLOW-UP AB Objective: To make recommendations on the use of neoadjuvant or adjuvant therapy in addition to surgery in patients with resectable gastric cancer (T1-4, N1-2, MO). Options: Neoadjuvant or adjuvant treatments compared with "curative" surgery alone. Outcomes: Overall survival, disease-free survival, and adverse effects. Evidence: The MEDLINE, CANCERLIT and Cochrane Library databases and relevant conference proceedings were searched to identify randomized trials. Values: Evidence was selected and reviewed by one member of the Cancer Care Ontario Practice Guidelines Initiative (CCOPGI) Gastrointestinal Cancer Disease Site Group and methodologists. A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. This report has been reviewed and approved by the Gastrointestinal Cancer Disease Site Group, comprising medical oncologists, radiation oncologists, surgeons, a pathologist and 2 community representatives. Benefits, harms and costs: When compared with surgery alone, at 3 years adjuvant chemoradiotherapy has been shown to increase overall survival by 9% (50% v. 41%, p = 0.005) and to improve relapse-free survival from 31% to 48% (p = 0.001). At 5 years, it has been shown to increase overall survival by 11.6%(40% v. 28.4%) and to improve relapse-free survival from 25% to 38% (p < 0.001). Treatment has been associated with toxic deaths in 1% of patients. The most frequent adverse effects (> grade 3 [Southwest Oncology Group toxicity scale] arc hematologic (54%), gastrointestinal (33%), influenza-like (9%), infectious (6%) and neurologic (4%). The radiation fields used can possibly damage the left kidney, resulting in hypertension and other renal problems. Furthermore, this therapy could increase the demand on radiation resources. Physicians and patients should understand the tradeoffs between survival benefit and toxicity and cost before making treatment decisions. Recommendations: After surgical resection, patients whose tumours have penetrated the muscularis propria or involve regional lymph nodes should be considered for adjuvant combined chemoradiotherapy. The current standard protocol consists of 1 cycle of 5-fluorouracil (5-FU) (425 mg/m(2) daily) and leucovorin (20 mg/m(2) daily) administered daily for 5 days, followed 1 month later by 45 Gy (f.8 Gy/d) of radiation given with 5-FU (400 mg/m(2) daily) and leucovorin (20 mg/m(2) daily) on days 1 through 4 and the last 3 days of radiation. One month after completion of radiation, 2 cycles of 5-FU (425 mg/m2 daily) and leucovorin (20 mg/m(2) daily) in a daily regimen for 5 days are given at monthly intervals. There is no evidence on which to make a recommendation for patients with node-negative tumours that have not penetrated the muscularis propria. For patients unable to undergo radiation, adjuvant chemotherapy alone may be of benefit, particularly for those with lymph-node metastases. The optimal regimen remains to be defined. There is insufficient evidence from randomized trials to recommend neoadjuvant chemotherapy, or neoadjuvant or adjuvant radiotherapy or immunotherapy, either alone or in combination, outside a clinical trial. Validation: A draft version of this document was circulated to 166 clinicians using a 21-item feedback questionnaire. Ninety-nine (63%) returned the questionnaire, and 74 of these indicated that the guideline was relevant to their clinical practice and completed the survey. Of the 74 clinicians, 52 (70%) Sponsors: The CCOPGI is supported by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care. C1 Ottawa Reg Canc Ctr, Gen Div, Gastrointestinal Canc Dis Site Grp, Ottawa, ON K1H 8L6, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. McMaster Univ, Canc Care Ontario Practice Guidelines Initiat, Hamilton, ON, Canada. RP Maroun, J (reprint author), Ottawa Reg Canc Ctr, Gen Div, Gastrointestinal Canc Dis Site Grp, 501 Smuth Rd, Ottawa, ON K1H 8L6, Canada. NR 73 TC 17 Z9 17 U1 0 U2 2 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0008-428X J9 CAN J SURG JI Can. J. Surg. PD DEC PY 2002 VL 45 IS 6 BP 438 EP 446 PG 9 WC Surgery SC Surgery GA 622YJ UT WOS:000179675300009 PM 12500920 ER PT J AU Palmer, RE Lee, SB Wong, JC Reynolds, PA Zhang, H Truong, V Oliner, JD Gerald, WL Haber, DA AF Palmer, RE Lee, SB Wong, JC Reynolds, PA Zhang, H Truong, V Oliner, JD Gerald, WL Haber, DA TI Induction of BAIAP3 by the EWS-WT1 chimeric fusion implicates regulated exocytosis in tumorigenesis SO CANCER CELL LA English DT Article ID ROUND-CELL TUMOR; FIBROBLAST-GROWTH-FACTOR; BOVINE CHROMAFFIN CELLS; TRANSCRIPTIONAL ACTIVATOR; DNA-BINDING; WILMS-TUMOR; SUPPRESSOR GENE; PC12 CELLS; WT1 GENE; PROTEIN AB Desmoplastic small round cell tumor (DSRCT) is defined genetically by the chimeric fusion of the Ewing's sarcoma and Wilms' tumor genes, generating a novel transcription factor, EWS-WT1. By using cells with inducible EWS-WT1 to screen high-density microarrays, we identified BAIAP3 as a transcriptional target of the chimera. The BAIAP3 promoter is specifically bound in vivo by the (-KTS) isoform of EWS-WT1, consistent with its activation in reporter assays. BAIAP3 encodes a protein implicated in regulated exocytosis, which is colocalized with a secreted growth factor within cytoplasmic organelles. Ectopic expression of BAIAP3 in tumor cells dramatically enhances growth in low serum and colony formation in soft agar. BAIAP3 therefore encodes a transcriptional target of an oncogenic fusion protein that implicates the regulated exocytotic pathway in cancer cell proliferation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Affymetrix, Santa Clara, CA 95051 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA90627] NR 44 TC 42 Z9 42 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2002 VL 2 IS 6 BP 497 EP 505 DI 10.1016/S1535-6108(02)00205-2 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 629MD UT WOS:000180052700011 PM 12498718 ER PT J AU Xu, LL Liu, G Miller, DP Zhou, W Lynch, TJ Wain, JC Su, L Christiani, DC AF Xu, LL Liu, G Miller, DP Zhou, W Lynch, TJ Wain, JC Su, L Christiani, DC TI Counterpoint: The myeloperoxidase (-463)G -> A polymorphism does not decrease lung cancer susceptibility in Caucasians SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID CIGARETTE-SMOKING; GENETIC-VARIANTS; RISK; LAVAGE; ASSOCIATION; SMOKERS; REGION; DNA AB The myeloperoxidase (MPO) G-to-A substitution polymorphism in the promoter region of the MPO gene has been associated with a 40-70% reduction in lung cancer risk in several studies, although a recent nested case-control study disputes these findings. MPO is involved in the activation of a number of procarcinogens, including benzo(a)pyrene. The variant A allele has been shown to reduce MPO mRNA expression, thus potentially decreasing carcinogen activation. To confirm results from smaller studies, we evaluated this MPO polymorphism in 988 incident Caucasian lung cancer cases and 1128 controls. Logistic regression evaluated the association between MPO genotype and lung cancer risk, adjusting for age, gender, smoking status, time since quitting smoking, and pack-years of smoking. In the controls, the A allele frequency was 21%, and genotype distribution was in the Hardy-Weinberg equilibrium. Compared with the wild-type GIG genotype, the adjusted odds ratios for the A/A and A/G genotypes were 1.15 (95% confidence interval 0.7-1.9, P > 0.2) and 1.03 (95% confidence interval 0.8-1.3, P > 0.20), respectively. A similar lack of association was seen in analyses stratified by smoking status, median age, a number of smoking variables, disease stage, tumor grade, and histological subtype. These findings are in contrast with earlier studies suggesting a protective effect of carrying the variant A allele. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 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, Ctr Canc,Div Hematol Oncol,Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Unit Med, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES00002, ES/CA06409, ES T3207069] NR 26 TC 52 Z9 53 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2002 VL 11 IS 12 BP 1555 EP 1559 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 628UE UT WOS:000180014300005 PM 12496043 ER PT J AU Varghese, S Rabkin, SD AF Varghese, S Rabkin, SD TI Oncolytic herpes simplex virus vectors for cancer virotherapy SO CANCER GENE THERAPY LA English DT Review DE HSV; cancer therapy; clinical trials; oncolytic virus ID REPLICATION-SELECTIVE ADENOVIRUS; EPITHELIAL OVARIAN-CANCER; SQUAMOUS-CELL CARCINOMA; THYMIDINE KINASE GENE; LONG-TERM SURVIVAL; TYPE-1 MUTANT G207; PHASE-I TRIAL; RIBONUCLEOTIDE REDUCTASE; ANTITUMOR-ACTIVITY; PROSTATE-CANCER AB Oncolytic herpes simplex virus type 1 (HSV-1) vectors are emerging as an effective and powerful therapeutic approach for cancer. Replication-competent HSV-1 vectors with mutations in genes that affect viral replication, neuropathogenicity, and immune evasiveness have been developed and tested for their safety and efficacy in a variety of mouse models. Evidence to-date following administration into the brain attests to their safety, an important observation in light of the neuropathogenicity of the virus. Phase I clinical traits of three vectors, G207, 1716, and NV1020, are either ongoing or completed, with no adverse events attributed to the virus. These and other HSV-1 vectors are effective against a myriad of solid tumors in mice, including glioma, melanoma, breast, prostate, colon, ovarian, and pancreatic cancer. Enhancement of activity was observed when HSV-1 vectors were used in combination with traditional therapies such as radiotherapy and chemotherapy, providing an attractive strategy to pursue in the clinic. Oncolytic HSV-1 vectors expressing "suicide" genes (thymidine kinase, cytosine deaminase, rat cytochrome P450) or immunostimulatory genes (IL-12, GM-CSF, etc.) have been constructed to maximize tumor destruction through multimodal therapeutic mechanisms. Further advances in virus delivery and tumor specificity should improve the likelihood for successful translation to the clinic. C1 Massachusetts Gen Hosp, Mol Neurosurg Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, 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 [NS32677, NS33342] NR 125 TC 159 Z9 166 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD DEC PY 2002 VL 9 IS 12 BP 967 EP 978 DI 10.1038/sj.cgt.7700537 PG 12 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 625CV UT WOS:000179800100003 PM 12522436 ER PT J AU Bar-Shira, A Pinthus, JH Rozovsky, U Goldstein, M Sellers, WR Yaron, Y Eshhar, Z Orr-Urtreger, A AF Bar-Shira, A Pinthus, JH Rozovsky, U Goldstein, M Sellers, WR Yaron, Y Eshhar, Z Orr-Urtreger, A TI Multiple genes in human 20q13 chromosomal region are involved in an advanced prostate cancer xenograft SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; APOPTOSIS SUSCEPTIBILITY GENE; CELL-LINES; BREAST CANCERS; EXPRESSION; AMPLIFICATIONS; PROGRESSION AB We analyzed a prostate cancer xenograft derived from a locally advanced tumor using combined cytogenetic, array-based comparative genomic hybridization and expression analyses. This analysis revealed that genes in the 20q13 chromosomal region, CSE1L, ZNF217, MYBL2, and STK15, were significantly overexpressed in this tumor. The expression pattern of these genes was then confirmed in two large human prostate cancer microarray databases. Furthermore, the MYBL2 and STK15 have been significantly overexpressed in prostate metastases, allowing a clear distinction between localized tumors and metastases. Our data suggest these genes to be involved in advanced stages of prostate tumorigenesis and as such, they may serve as markers for tumor progression. C1 Tel Aviv Sourasky Med Ctr, IL-64239 Tel Aviv, Israel. Tel Aviv Univ, Fac Med, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Orr-Urtreger, A (reprint author), Tel Aviv Sourasky Med Ctr, 6 Weizmann St, IL-64239 Tel Aviv, Israel. NR 33 TC 81 Z9 92 U1 1 U2 4 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 DEC 1 PY 2002 VL 62 IS 23 BP 6803 EP 6807 PG 5 WC Oncology SC Oncology GA 622HJ UT WOS:000179641000003 PM 12460888 ER PT J AU Campbell, RB Fukumura, D Brown, EB Mazzola, LM Izumi, Y Jain, RK Torchilin, VP Munn, LL AF Campbell, RB Fukumura, D Brown, EB Mazzola, LM Izumi, Y Jain, RK Torchilin, VP Munn, LL TI Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors SO CANCER RESEARCH LA English DT Article ID CELLS; PERMEABILITY; DEPENDENCE; XENOGRAFT; PATHWAYS; VESSELS AB Tumor vessels possess unique physiological features that might be exploited for improving drug delivery. In the present study, we investigate the possibility of modifying polyethylene glycol-ylated liposome cationic charge of polyethylene glycol coated liposomes to optimize delivery to tumor vessels using biodistribution studies and intravital microscopy. The majority of liposomes accumulated in the liver, and increasing charge resulted in lower retention in the spleen and blood. Although overall tumor uptake was not affected by charge in the biodistribution studies, intravital microscopy showed that increasing the charge content from 10 to 50 mol % doubled the accumulation of liposomes in tumor vessels, suggesting a change in intratumor distribution; no significant effect of charge on interstitial accumulation could be detected, possibly attributable to spatial heterogeneity. Increased vascular accumulation of cationic liposomes was similar in two different tumor types and sites. Our results suggest that optimizing physicochemical properties of liposomes that exploit physiological features of tumors and control the intratumor distribution of these drug carriers should improve vascular-specific delivery. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [P01-CA80124, P01 CA080124-01A1S10002, P01 CA080124-01A19001, T32-CA73479] NR 24 TC 199 Z9 207 U1 9 U2 32 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 DEC 1 PY 2002 VL 62 IS 23 BP 6831 EP 6836 PG 6 WC Oncology SC Oncology GA 622HJ UT WOS:000179641000010 PM 12460895 ER PT J AU Naoki, K Chen, TH Richards, WG Sugarbaker, DJ Meyerson, M AF Naoki, K Chen, TH Richards, WG Sugarbaker, DJ Meyerson, M TI Missense mutations of the BRAF gene in human lung adenocarcinoma SO CANCER RESEARCH LA English DT Article ID NIH 3T3 CELLS; CYCLIN D1; EXPRESSION; CANCER; PROLIFERATION; PROGRESSION; INHIBITOR; KINASE; LEVEL AB Mutations of the BRAF protein serine/threonine kinase gene have recently been identified in a variety of human cancers, most notably melanomas. We sought to determine the frequency of BRAF mutations in human lung cancer pathogenesis. Analysis of BRAF sequence from 127 primary human lung adenocarcinomas revealed mutations in two tumor specimens, one in exon 11 (G465V), and a second in exon 15 (1,59611). These specimens belong to the same adenocarcinoma subgroup as defined by clustering of gene expression data. BRAF may provide a target for anticancer chemotherapy in a subset of lung adenocarcinoma patients. C1 Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Room M430,44 Binney St, Boston, MA 02115 USA. RI Meyerson, Matthew/E-7123-2012 NR 19 TC 198 Z9 206 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 DEC 1 PY 2002 VL 62 IS 23 BP 7001 EP 7003 PG 3 WC Oncology SC Oncology GA 622HJ UT WOS:000179641000034 PM 12460919 ER PT J AU Bauer, KA Hawkins, DW Peters, PC Petitou, M Herbert, JM van Boeckel, CAA Meuleman, DG AF Bauer, KA Hawkins, DW Peters, PC Petitou, M Herbert, JM van Boeckel, CAA Meuleman, DG TI Fondaparinux, a synthetic pentasaccharide: The first in a new class of antithrombotic agents - The selective factor Xa inhibitors SO CARDIOVASCULAR DRUG REVIEWS LA English DT Review DE antithrombin; factor Xa; fondaparinux sodium; pentasaccharide; thrombosis ID DEEP-VEIN THROMBOSIS; HEPARIN-INDUCED THROMBOCYTOPENIA; MOLECULAR-WEIGHT HEPARINS; III BINDING FRAGMENT; HIGH-AFFINITY; VENOUS THROMBOEMBOLISM; UNFRACTIONATED HEPARIN; CONFORMATIONAL CHANGE; PULMONARY-EMBOLISM; STANDARD HEPARIN AB Despite currently available antithrombotic therapies, venous thromboembolism (VTE) remains a major cause of morbidity and mortality. Fondaparinux sodium (pentasaccharide), the first in a new class of antithrombotic agents developed for the prevention and treatment of VTE, inhibits thrombin generation by selectively inhibiting factor Xa. Fondaparinux exhibits complete bioavailability by the subcutaneous route and is rapidly absorbed, reaching its maximum concentration approximately 2 h post dosing. It has a terminal half-life of 13 to 21 h, permitting once-daily dosing. Fondaparinux's reproducible linear pharmacokinetic profile exhibits minimal intrasubject and intersubject variability, suggesting that individual dose adjustments will not be required for the vast majority of the population and that there will be no need for routine hemostatic monitoring. At therapeutic concentrations (<2 mg/L), fondaparinux exhibits >94% binding to its target protein, antithrombin. Within this same concentration range there is no specific binding by fondaparinux to plasma proteins commonly involved in drug binding, indicating a low potential for drug-drug interactions by protein displacement. Unlike antithrombotic agents prepared from animal extracts (heparins), fondaparinux is chemically synthesized; this leads to batch-to-batch consistency and the absence of potential risk of contamination problems. In recently completed phase III clinical trials in VTE prevention in major orthopedic Surgery, fondaparinux showed significant superiority over the low-molecular-weight heparin enoxaparin, providing an overall >50% (P < 0.001) reduction in VTE risk without increasing clinically important bleeding. Additional clinical data Support its potential benefits in other venous and arterial thrombotic disorders. In view of these collective findings, fondaparinux is expected to play a major role in the prevention and treatment of venous and arterial thrombotic disease. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Mercer Univ, So Sch Pharm, Atlanta, GA USA. WB Carrell Mem Clin, Dallas, TX USA. Sanofi Synthelabo, Toulouse, France. Organon, Oss, Netherlands. RP Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM Kbauer@caregroup.harvard.edu NR 77 TC 87 Z9 93 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0897-5957 J9 CARDIOVASC DRUG REV JI Cardiovasc. Drug Rev. PD WIN PY 2002 VL 20 IS 1 BP 37 EP 52 PG 16 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 564AH UT WOS:000176291000004 PM 12070533 ER PT J AU Singleton, PA Bourguignon, LYW AF Singleton, PA Bourguignon, LYW TI CD44v10 interaction with Rho-Kinase (ROK) activates inositol 1,4,5-triphosphate (IP3) receptor-mediated Ca2+ signaling during hyaluronan (HA)-induced endothelial cell migration SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE CD44; Rho-Kinase; IP3 receptors; Ca2+ signaling; hyaluronan; endothelial cell migration ID RECONSTITUTED LIPID VESICLES; ANKYRIN-BINDING DOMAIN; 1,4,5-TRISPHOSPHATE RECEPTOR; PROTEIN-KINASE; TYROSINE KINASES; BREAST-CANCER; TRANSMEMBRANE GLYCOPROTEIN; TRISPHOSPHATE RECEPTOR; ADP-RIBOSYLATION; FOCAL ADHESIONS AB Aortic endothelial cells (GM7372A) express a major cell adhesion molecule, CD44v10, which binds the extracellular matrix component, hyaluronan (HA), at its external domain and interacts with various signaling molecules at its cytoplasmic domain. In this study, we have determined that CD44v10 and Rho-Kinase (ROK) are physically associated as a complex in vivo. Using a recombinant fragment of ROK (in particular, the pleckstrin homology [PH] domain) and in vitro binding assays, we have detected a specific binding interaction between the PH domain of ROK and the cytoplasmic domain of CD44. Scatchard plot analysis indicates that there is a single high-affinity CD44 binding site in the PH domain of ROK with an apparent dissociation constant (Kd) of 1.76 nM, which is comparable to CD44 binding (Kd similar to 1.56 nM) to intact ROK. These findings suggest that the PH domain is the primary ROK binding region for CD44. Furthermore, HA binding to GM7372A cells promotes RhoA-mediated ROK activity, which, in turn, increases phosphorylation of three different inositol 1, 4, 5-trisphosphate receptors (IP(3)Rs) [in particular, subtype 1 (IP(3)R1), and to a lesser extent subtype 2 (IP(3)R2) and subtype 3 (IP(3)R3)] all known as Ip(3)-gated Ca2+ channels. The phosphorylated IP(3)R1 (but not IP(3)R2 or IP(3)R3) is enhanced in its binding to IP3 which subsequently stimulates IP3-mediated Ca2+ flux. Transfection of the endothelial cells with ROK's PH cDNA significantly reduces ROK association with CD44v10, and effectively inhibits ROK-mediated phosphorylation of IP(3)Rs and IP3R-mediated Ca2+ flux in vitro. The PH domain of ROK also functions as a dominant-negative mutant in vivo to block HA-dependent, CD44v10-specific intracellular Ca2+ mobilization and endothelial cell migration. Taken together, we believe that CD44v10 interaction with ROK plays a pivotal role in IP3R-mediated Ca2+ signaling during HA-mediated endothelial cell migration. (C) 2002 Wiley-Liss, Inc. C1 Univ Calif San Francisco, Dept Med, Endocrine Unit 111N, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Bourguignon, LYW (reprint author), Univ Calif San Francisco, Dept Med, Endocrine Unit 111N, San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. FU NCI NIH HHS [CA66163, CA78633] NR 85 TC 56 Z9 56 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD DEC PY 2002 VL 53 IS 4 BP 293 EP 316 DI 10.1002/cm.10078 PG 24 WC Cell Biology SC Cell Biology GA 616QG UT WOS:000179314000006 PM 12378540 ER PT J AU Wilhelm, M Fishman, JA Pontikis, R Aubertin, AM Wilhelm, FX AF Wilhelm, M Fishman, JA Pontikis, R Aubertin, AM Wilhelm, FX TI Susceptibility of recombinant porcine endogenous retrovirus reverse transcriptase to nucleoside and non-nucleoside inhibitors SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE porcine endogenous retrovirus; reverse transcriptase; inhibitors ID HUMAN-CELLS; MINIATURE SWINE; CLONED PIGS; INFECTION; IDENTIFICATION; EXPRESSION; POLYMERASE; SEQUENCES; ELEMENTS; GENOMES AB Transplantation of organs, tissues or cells from pigs to humans could be a potential solution to the shortage of human organs for transplantation. Porcine endogenous retroviruses (PERVs) remain a major safety concern for porcine xenotransplantation. Thus, finding drugs that could be used as virological prophylaxis (or therapy) against PERV replication would be desirable. One of the most effective ways to block retroviral multiplication Is to inhibit the enzyme reverse transcriptase (RT) which catalyzes the reverse transcription of viral RNA to proviral double-stranded DNA, We report here the cloning and expression of PERV RT and its susceptibility to several inhibitors, Our data demonstrate PERV susceptibility in vitro to the triphosphorylated nucleoside analog of zidovucline (AZT) and to ddGTP and to a lesser extent to ddTTP but almost no susceptibility to the non-nucleoside RT inhibitors tested. C1 Inst Biol Mol & Cellulaire, F-67084 Strasbourg, France. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Curie, CNRS, UMR 176, F-75231 Paris, France. INSERM, U 74, Inst Virol, F-67085 Strasbourg, France. RP Wilhelm, FX (reprint author), Inst Biol Mol & Cellulaire, 15,Rue Rene Descartes, F-67084 Strasbourg, France. FU NIAID NIH HHS [P01-AI45897] NR 33 TC 16 Z9 16 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD DEC PY 2002 VL 59 IS 12 BP 2184 EP 2190 DI 10.1007/s000180200017 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 639JM UT WOS:000180625000019 PM 12568344 ER PT J AU Vidal, M Boulton, SJ Bartner, A Reboul, J Vaglio, P Dyson, N Hill, DE AF Vidal, M Boulton, SJ Bartner, A Reboul, J Vaglio, P Dyson, N Hill, DE TI Combined functional genomic maps of the C-elegans DNA damage response SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the American-Chemical-Society Division of Chemical Toxicology at the 224th ACS National Meeting CY AUG 18-22, 2002 CL BOSTON, MA SP Amer Chem Soc, Div Chem Toxicol C1 Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Max Planck Inst Biochem, D-82152 Martinsried, Germany. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM marc_vidal@DFCI.harvard.edu RI Hill, David/B-6617-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 MA 6 BP 1653 EP 1653 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500026 ER PT J AU Castagnoli, N Petzer, JP Castagnoli, K Schwarzschild, MA Chen, JF AF Castagnoli, N Petzer, JP Castagnoli, K Schwarzschild, MA Chen, JF TI Inhibition of monoamine oxidase B by selective A(2A) adenosine receptor antagonists. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the American-Chemical-Society Division of Chemical Toxicology of the 224th ACS National Meeting CY AUG 18-22, 2002 CL BOSTON, MASSACHUSETTS SP Amer Chem Soc, Div Chem Toxicol C1 Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Med & Dent New Jersey, Dept Neurol, Newark, NJ 07103 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 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 MA 49 BP 1663 EP 1663 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500069 ER PT J AU Ciacci, C Di Vizio, D Seth, R Insabato, G Mazzacca, G Podolsky, DK Mahida, YR AF Ciacci, C Di Vizio, D Seth, R Insabato, G Mazzacca, G Podolsky, DK Mahida, YR TI Selective reduction of intestinal trefoil factor in untreated coeliac disease SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE goblet cells; trefoil peptides; gluten-sensitive enteropathy ID HUMAN SPASMOLYTIC POLYPEPTIDE; INFLAMMATORY BOWEL-DISEASE; HUMAN RESPIRATORY-TRACT; EPITHELIAL-CELLS; MONOCLONAL-ANTIBODIES; GENE-EXPRESSION; CELIAC-DISEASE; PEPTIDES; MUCIN; MICE AB The trefoil factor family (TFF) encompasses small peptides of which intestinal trefoil factor (ITF) is expressed specifically in goblet cells of the small and large intestine. Previous studies have shown that ITF plays an important role in mucosal protection and repair. Coeliac disease represents a model of immune-mediated small intestinal inflammation and damage, with recovery on gluten-free diet. The aim of this study was to investigate the expression of ITF in the distal duodenal mucosa of subjects with coeliac disease, before and after treatment with a gluten-free diet. Expression of ITF and mucin in the distal duodenal biopsies from treated (n = 11) and untreated (n = 9) coeliac subjects and controls (n = 8) was investigated by immunohistochemistry and semiquantitative PCR. In untreated coeliac disease, there was reduction of ITF immunoreactivity in goblet cells but mucin expression was preserved. Mucosal recovery on gluten-free diet was associated with increased ITF immunoreactivity in goblet cells. There was also reduction in the expression of ITF transcripts, relative to MUC2 mRNA, in untreated coeliac duodenal samples, with recovery on gluten-free diet. Our study suggests that there is a selective reduction in the expression of the ITF gene in untreated coeliac disease. Recovery of ITF expression on a gluten-free diet suggests that the mucosal immune system regulates goblet cell differentiation and ITF expression in the human intestinal mucosa. C1 Univ Hosp, Queens Med Ctr, Div Gastroenterol, Nottingham NG7 2UH, England. Univ Naples Federico II, Div Gastroenterol, Naples, Italy. Univ Naples Federico II, Div Pathol, Naples, Italy. Univ Hosp, Queens Med Ctr, Div Pathol, Nottingham NG7 2UH, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Mahida, YR (reprint author), Univ Hosp, Queens Med Ctr, Div Gastroenterol, Nottingham NG7 2UH, England. RI ciacci, carolina/A-2594-2012 OI ciacci, carolina/0000-0002-7426-1145 NR 42 TC 16 Z9 18 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD DEC PY 2002 VL 130 IS 3 BP 526 EP 531 DI 10.1046/j.1365-2249.2002.02011.x PG 6 WC Immunology SC Immunology GA 618GG UT WOS:000179409900023 PM 12452845 ER PT J AU Fisman, DN Agrawal, D Leder, K AF Fisman, DN Agrawal, D Leder, K TI The effect of age on immunologic response to recombinant hepatitis B vaccine: A meta-analysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HEALTH-CARE WORKERS; IMMUNE-SYSTEM; HEMODIALYSIS-PATIENTS; ANTIBODY-RESPONSE; METAANALYSIS; IMMUNOGENICITY; SEROCONVERSION; RESPONSIVENESS; IMMUNIZATION; EXPERIENCE AB Hepatitis B vaccine is a key tool for the prevention of hepatitis B infection. Age-associated changes in immune function may contribute to decreased vaccine efficacy in older individuals, although research related to this topic has yielded contradictory findings. We performed a meta-analysis of 24 published trials and studies that evaluated the association of age with response to hepatitis B vaccine, using a random-effects model. Pooling of study results suggested a significantly increased risk of nonresponse to hepatitis B vaccine among older individuals (relative risk [RR], 1.76; 95% confidence interval [Cl], 1.48-2.10). An elevated risk of nonresponse persisted even after exclusion of poor-quality studies (RR, 1.63; 95% Cl, 1.23-2.15) and adjustment for publication bias (RR, 1.52; 95% Cl, 1.26-1.83), and it was present even when "older" individuals were defined as being as young as 30 years. These findings have important implications for individuals at risk for hepatitis B infection, including health care workers and travelers. C1 City Hamilton Social & Publ Hlth Serv Dept, Hamilton, ON L8R 3L5, Canada. McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. Massachusetts Gen Hosp, Charlestown, MA USA. Monash Univ, Dept Epidemiol & Prevent Med, Clayton, Vic 3168, Australia. RP Fisman, DN (reprint author), City Hamilton Social & Publ Hlth Serv Dept, 1 Hughson St N,4th Fl, Hamilton, ON L8R 3L5, Canada. OI Leder, Karin/0000-0003-1368-1039 NR 45 TC 95 Z9 109 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2002 VL 35 IS 11 BP 1368 EP 1375 DI 10.1086/344271 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 617AK UT WOS:000179336800010 PM 12439800 ER PT J AU Kahkonen, S Ahveninen, J Pekkonen, E Kaakkola, S Huttunen, J Ilmoniemi, RJ Jaaskelainen, IP AF Kahkonen, S Ahveninen, J Pekkonen, E Kaakkola, S Huttunen, J Ilmoniemi, RJ Jaaskelainen, IP TI Dopamine modulates involuntary attention shifting and reorienting: an electromagnetic study SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE attention; auditory event-related responses; dopamine; electroencephalography; haloperidol; magnetoencephalography ID AUDITORY SELECTIVE ATTENTION; WHOLE-HEAD MEG; MISMATCH NEGATIVITY; INCREASED DISTRACTIBILITY; SCHIZOPHRENIC-PATIENTS; MAGNETIC-FIELDS; HUMAN-BRAIN; HALOPERIDOL; POTENTIALS; EEG AB Objective: Dopaminergic function has been closely associated with attentional performance, but its precise role has remained elusive. Methods: Electrophysiological and behavioral methods were used to assess the effects of dopamine D2-receptor antagonist haloperidol on involuntary attention shifting using a randomized, double-blind, placebo-controlled cross-over design. Eleven subjects were instructed to discriminate equiprobable 200 and 400 ms tones in a forced-choice reaction-time (RT) task during simultaneous measurement of whole-head magnetoencephalography and high-resolution electroencephalography. Results: Occasional changes in task-irrelevant tone frequency (10% increase or decrease) caused marked distraction on behavioral performance, as shown by significant RT increases to deviant stimuli and subsequent standard tones. Furthermore, while the standard tones elicited distinct P1-N1-P2-N2-P3 waveforms, deviant tones elicited additional mismatch negativity (MMN), P3a, and reorienting negativity (RON) responses, indexing brain events associated with involuntary attention shifting. While haloperidol did not affect the source loci of the responses of magnetic N1 and MMN, the amplitude of the electric P3a and that of RON were significantly reduced and the latency of magnetic RON were delayed following haloperidol administration. Conclusions: The present results suggest that dopamine modulates involuntary attention shifting to task-irrelevant deviant events. It appears that dopamine may disrupt the subsequent re-orienting efforts to the relevant task after distraction. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Helsinki, Dept Psychol, Cognitive Brain Res Unit, Helsinki, Finland. Univ Helsinki, Cent Hosp, BioMag Lab, Engn Ctr, FIN-00029 HUS, Finland. Univ Helsinki, Helsinki Brain Res Ctr, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00029 HUS, Finland. Univ Helsinki, Cent Hosp, Dept Clin Neurophysiol, FIN-00029 HUS, Finland. Harvard Univ, Sch Med, NMR Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. Univ Helsinki, Dept Psychol, Appercept & Cort Dynam Res Team, Helsinki, Finland. RP Kahkonen, S (reprint author), Univ Helsinki, Dept Psychol, Cognitive Brain Res Unit, Helsinki, Finland. RI Jaaskelainen, Iiro/C-7392-2012; Ilmoniemi, Risto/E-9704-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Ilmoniemi, Risto/0000-0002-3340-2618 NR 41 TC 61 Z9 61 U1 1 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD DEC PY 2002 VL 113 IS 12 BP 1894 EP 1902 AR PII S1388-2457(02)00305-X DI 10.1016/S1388-2457(02)00305-X PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 626NA UT WOS:000179878000003 PM 12464326 ER PT J AU Thase, ME Sachs, GS AF Thase, ME Sachs, GS TI The challenges of pharmacotherapy of bipolar depression SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE antidepressants; mood stabilizers; olanzapine; bipolar depression; lamotrigine ID SEROTONIN REUPTAKE INHIBITORS; DOUBLE-BLIND; LITHIUM-CARBONATE; MAJOR DEPRESSION; DISORDER; IMIPRAMINE; PLACEBO; TRANYLCYPROMINE; ANTIDEPRESSANT; BUPROPION AB Bipolar depression is disabling and its treatment represents a major challenge to clinicians. This article briefly reviews the major pharmacological treatment options. Use of mood stabilizers as the initial treatment for the type I form of bipolar depression is strongly recommended, particularly because preventive therapy with these agents almost certainly will be subsequently indicated. It is less clear if mood stabilizers are necessary for bipolar type 11 depression, aside from the rapid cycling presentation. Depressive episodes that do not respond to mood stabilizers, as well as episodes that 'break-through' despite prophylactic therapy, warrant treatment with antidepressants. Experts similarly value earlier use of antidepressants when depressive episodes are overwhelmingly severe or, in combination with neuroleptics, psychotic. Among antidepressants, bupropion and the Selective Serotonin Reuptake Inhibitors (SSRIs) are considered by expert panels as coequal first choices, with venlafaxine and the monoamine oxidase inhibitor tranylcypromine preferred for more resistant cases. The risk of antidepressant-induced hypomania or mania with concomitant mood stabilizer therapy is low, on the order of 5-10% during acute phase therapy with a SSRI or bupropion. The optimal duration of successful antidepressant therapy has not been determined. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thase, ME (reprint author), Univ Pittsburgh, Med Ctr, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. NR 67 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2002 VL 2 IS 3-4 BP 213 EP 221 AR PII S1566-2772(02)00045-2 DI 10.1016/S1566-2772(02)00045-2 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633GE UT WOS:000180273600010 ER PT J AU Maloney, WJ Schmalzried, T Harris, WH AF Maloney, WJ Schmalzried, T Harris, WH TI Analysis of long-term cemented total hip arthroplasty retrievals SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 8th Meeting of the Hip-Society CY SEP 05-07, 2002 CL ROCHESTER, MN SP Hip Soc ID FEMORAL COMPONENTS; REPLACEMENT; PROSTHESES; STRESS; DISTRIBUTIONS; INVITRO AB A detailed biomechanical, histologic, and histomorphometric analysis of autopsy specimens from patients who previously had cemented total hip arthroplasty has helped to elucidate the skeletal response to cemented components. Bone cement has the capacity to provide long-term implant stability. The biologic response to polyethylene wear debris has a more critical effect on destabilization of cemented sockets compared with the femoral side. In contrast, mechanical events tended to predominate the early mode of destabilization of cemented femoral components with debonding at the metal-cement interface and fracture in the cement. Fractures predominate in cement mantles less than I mm thick and are associated with mantle defects, debonded interfaces, and sharp corners of the implants. Correlation of the histologic findings at the cementbone interface with radiolucencies seen on clinical radiographs show that on the acetabular side radiolucencies represent a soft tissue membrane that is the biologic response to polyethylene debris. In contrast, on the femoral side, most radiolucencies were as a result of skeletal remodeling. Femoral adaptive bone remodeling is a diffuse process that occurs over the entire fixation surface. The most profound disuse osteoporosis occurred proximally in the proximal medial quadrant; however, when one takes into account all four quadrants, anterior, posterior, medial, and lateral, the most severe osteoporosis occurred at the midpoint of the stem. C1 Washington Univ, Barnes Jewish Hosp, Dept Orthopaed Surg, Sch Med, St Louis, MO 63110 USA. Orthoped Hosp, Joint Replacement Inst, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Washington Univ, Barnes Jewish Hosp, Dept Orthopaed Surg, Sch Med, Campus Box 8233,660 S Euclid, St Louis, MO 63110 USA. EM maloneyw@msnotes.wustl.edu NR 37 TC 46 Z9 51 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2002 IS 405 BP 70 EP 78 DI 10.1097/01.blo.0000038060.29678.90 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 626FK UT WOS:000179861400009 PM 12461358 ER PT J AU Burroughs, BR Rubash, HE Harris, WH AF Burroughs, BR Rubash, HE Harris, WH TI Femoral head sizes larger than 32 mm against highly cross-linked polyethylene SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 8th Meeting of the Hip-Society CY SEP 05-07, 2002 CL ROCHESTER, MINNESOTA SP Hip Soc ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-REPLACEMENT; ON-DISK DEVICE; WEAR; ARTHROPLASTY; UHMWPE AB The advent of highly cross-linked ultrahigh molecular weight polyethylene, which shows extremely low wear independent of head size in vitro, allows for the reevaluation of the use of femoral heads larger than 32 mm. The current authors discuss information that supports this hypothesis. The supporting information includes in vitro wear testing and in vitro anatomic studies, and prior clinical studies in which large femoral heads were used. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson 1126,55 Fruit St, Boston, MA 02114 USA. NR 31 TC 42 Z9 45 U1 0 U2 4 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 DEC PY 2002 IS 405 BP 150 EP 157 DI 10.1097/01.blo.0000038475.05771.b7 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 626FK UT WOS:000179861400018 PM 12461367 ER PT J AU Swenson, ER Deem, S Kerr, ME Bidani, A AF Swenson, ER Deem, S Kerr, ME Bidani, A TI Inhibition of aquaporin-mediated CO2 diffusion and voltage-gated H+ channels by zinc does not alter rabbit lung CO2 and NO excretion SO CLINICAL SCIENCE LA English DT Article DE aquaporin; carbon dioxide; carbonic anhydrase; gas exchange; lungs; nitric oxide; rabbit; voltage-gated H+ channels ID CARBONIC-ANHYDRASE; WATER CHANNELS; PERMEABILITY; EXCHANGE; TRANSPORT; O2 AB Aquaporins (AQs) increase cell membrane CO2 diffusivity, and it has been proposed that they may serve as transmembrane channels for CO2 and other small gas molecules. In addition, it has been hypothesized that voltage-gated H+ channels located on the apical membrane of the alveolar epithelium contribute to CO2 elimination by the lung. To test whether these membrane proteins contribute to CO2 elimination in vivo, we measured CO2 exchange in buffer- and blood-perfused rabbit lungs before and after addition of 0.5 mM ZnCl2, an inhibitor of both AQ-mediated CO2 diffusion and voltage-gated H+ channels. For comparison, red cell and lung carbonic anhydrases (CAs) were inhibited by 0.1 mM methazolamide. ZnCl2 had no effect on CO2 exchange when inspired CO2 was altered between 2% and 5% in 5-min intervals. Pulmonary vascular and airway resistances were not altered by ZnCl2. In contrast, methazolamide inhibited CO2 exchange by 30% in buffer-perfused lungs and by 65% in blood-perfused lungs. Exhaled NO concentrations were unaffected by ZnCl2 or by CA inhibition. Lung capillary gas exchange modelling shows that under normal resting conditions it would be necessary to reduce the alveolar-capillary membrane CO2 diffusion capacity by > 90% to lower CO2 elimination by 10%. Therefore we conclude that red cell and lung AQs and voltage-gated H+ channels in the alveolar epithelium contribute minimally to normal physiological CO2 elimination. C1 Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Anesthesiol, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Texas, Hlth Sci Ctr, Div Pulm Crit Care Med & Sleep Med, Houston, TX 77550 USA. RP Swenson, ER (reprint author), Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL 45571, HL 51421, HL 03796-01] NR 36 TC 15 Z9 16 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD DEC PY 2002 VL 103 IS 6 BP 567 EP 575 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 625TW UT WOS:000179832500005 PM 12444909 ER PT J AU Mares, AS Young, AS McGuire, JF Rosenheck, RA AF Mares, AS Young, AS McGuire, JF Rosenheck, RA TI Residential environment and quality of life among seriously mentally ill residents of board and care homes SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article; Proceedings Paper CT 5th Conference of the Society-for-Social-Work-and-Research CY JAN, 2001 CL ATLANTA, GEORGIA SP Soc Social Work & Res DE residential environment; board and care; social climate; quality of life ID OF-LIFE; SCHIZOPHRENIA; SYMPTOMS; SCALE AB This study examined the relationship between residential environment of seriously mentally ill patients living in board and care homes and quality of life. Participants included 162 seriously mentally ill veteran patients living in 26 board and care-homes in Los Angeles. Data from structured interviews were used to assess subjective quality of life (satisfaction with living situation and general well-being) and objective quality of life (social functioning and daily activities). Independent variables examined in multivariate analyses included individual socio-demographic and clinical characteristics, objective characteristics of the home, and subjective resident assessments of social climate within the home. Adjusting for individual characteristics, social climate was significantly and positively associated with both satisfaction with current living situation and with general well-being. Interpersonal conflict was negatively associated with general well-being. Number of beds within the home and median income in the neighborhood were significantly associated (positively and negatively, respectively) with social functioning outside the home. Living environment characteristics explained between 3 and 9% of the total variation in three of four quality of life measures, and 27% of the variation in the fourth, satisfaction with living situation. Satisfaction with living sittiation among seriously mentally ill residents of board and care homes may be enhanced by making the social climate more positive, and reducing conflict within the home. Social functioning outside of the home may be enhanced by placing patients into a home with more beds, and/or a home located in a lower income neighborhood. C1 VA CT Healthcare Syst, NE Program, Evaluat Ctr, NEPEC, West Haven, CT 06156 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Heathcare Syst, Los Angeles, CA USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. Yale Univ, Dept Publ Hlth, New Haven, CT 06520 USA. RP Mares, AS (reprint author), VA CT Healthcare Syst, NE Program, Evaluat Ctr, NEPEC, 182,950 Campbell Ave, West Haven, CT 06156 USA. RI Mares, Alvin/I-8186-2012; Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 NR 23 TC 15 Z9 15 U1 1 U2 2 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD DEC PY 2002 VL 38 IS 6 BP 447 EP 458 DI 10.1023/A:1020876000860 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 618QY UT WOS:000179429800002 PM 12474933 ER PT J AU Walter, RB Li, HY Intano, GW Kazianis, S Walter, CA AF Walter, RB Li, HY Intano, GW Kazianis, S Walter, CA TI Absence of global genomic cytosine methylation pattern erasure during medaka (Oryzias latipes) early embryo development SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE medaka; fish; methylcytosine; genomic DNA; methylation patterns; microinjection; embryogenesis; restriction analyses ID DNA METHYLATION; EXCISION-REPAIR; MOUSE EMBRYO; GENE; DEMETHYLATION; CELLS; 5-METHYLDEOXYCYTIDINE; EXPRESSION; ZEBRAFISH; ISLANDS AB Two techniques were used to analyze global genomic 5-methyl cytosine methylation at CCGG sites of medaka embryo DNA. DNA was labeled by incorporation of microinjected radiolabeled deoxynucleotide into one-cell embryos. After Hpa 11 or Msp I digestion the radiolabeled DNA was fractionated in agarose gels and the distribution of label quantified throughout each sample lane to detect differences in fragment distribution. Alternately isolated DNA was digested with Hpa 11 or Msp I and the resulting generated termini end-labeled. The end-labeled digestion products were then analyzed for fragment distribution after gel fractionation. These techniques proved to be extremely sensitive, allowing comparison of genomic DNA methylation values from as few as 640 fish cells. The data suggest that in medaka embryos the vast majority (> 90%) of genomic DNA is methylated at CCGG sites. Furthermore, these data support the conclusion that the extent of methylation at these sites does not change or changes very little during embryogenesis (from 16 cells to the hatchling). These data argue against active demethylation, or loss of methylation patterns by dilution, during the developmental stages between the one cell zygote and gastrulation. From a comparative viewpoint, these data may indicate that mammals and fishes methylate and demethylate their genomes in very different manners during development. (C) 2002 Elsevier Science Inc. All rights reserved. C1 SW Texas State Univ, Dept Biochem & Chem, San Marcos, TX 78666 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Walter, RB (reprint author), SW Texas State Univ, Dept Biochem & Chem, 419 Centennial Hall,601 Univ Dr, San Marcos, TX 78666 USA. FU NCI NIH HHS [CA75137]; NCRR NIH HHS [RR12253, RR17072]; NIEHS NIH HHS [ES09136] NR 31 TC 13 Z9 13 U1 3 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD DEC PY 2002 VL 133 IS 4 BP 597 EP 607 AR PII S1096-4959(02)00144-6 DI 10.1016/S1096-4959(02)00144-6 PG 11 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 629BL UT WOS:000180030500014 PM 12470822 ER PT J AU Sesso, HD Gaziano, JM VanDenburgh, M Hennekens, CH Glynn, RJ Buring, JE AF Sesso, HD Gaziano, JM VanDenburgh, M Hennekens, CH Glynn, RJ Buring, JE TI Comparison of baseline characteristics and mortality experience of participants and nonparticipants in a randomized clinical trial: the Physicians' Health Study SO CONTROLLED CLINICAL TRIALS LA English DT Article DE clinical trials; methodology; response rates; eligibility; willingness; run-in phase; mortality ID RUN-IN PERIODS; NATIONAL DEATH INDEX; CARDIOVASCULAR-DISEASE; RESPONSE RATES; BETA-CAROTENE; WILLINGNESS; ASPIRIN AB Although subjects randomized into clinical trials tend to have different mortality experiences from those not randomized, few studies have examined how baseline characteristics may explain these differences. We used the recruitment experience of the Physicians' Health Study (PHS) to describe and compare subgroups of subjects ultimately randomized-or not-into the PHS. A total of 112,528 male physicians ages 40-84 years responded to letters of invitation and baseline questionnaires. sent to 261,248 subjects. Baseline information was collected on eligibility criteria, plus lifestyle and clinical risk factors. Total, cardiovascular, cancer, and other mortality were determined through the National Death Index after a mean follow-up of 5.39 years. Respondents had 19 and 19% lower total and cardiovascular mortality rates than nonrespondents. Similarly, willing respondents were 19 and 16% less likely to die than unwilling respondents. However, much of this difference in mortality was explained by disease and lifestyle factors. Respondents who were eligible for the PHS had significantly lower age-adjusted relative risks (RRs) that were attenuated but remained substantially below 1 upon multivariate adjustment in models for total (RRs from 0.48 to 0.79), cardiovascular (from 0.40 to 0.85), and cancer mortality (from 0.55 to 0.87). Finally, a nearly halving in the age-adjusted risk of total and cause-specific mortality among men completing a run-in and randomized into PHS compared with those not randomized was nominally altered upon adding all covariates into multivariate models. In conclusion, a difference in mortality rates according to willingness to participate in a trial was explained by disease and lifestyle factors. In contrast, diseases and risk factors explain some, but not all, of the lower mortality rates of physicians based on eligibility status and their ability to complete a run-in phase. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Sesso, HD (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NCI NIH HHS [CA40360, CA34944]; NHLBI NIH HHS [HL42441, HL34595, HL26490] NR 31 TC 42 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 2002 VL 23 IS 6 BP 686 EP 702 AR PII S0197-2456(02)00235-0 DI 10.1016/S0197-2456(02)00235-0 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 625UZ UT WOS:000179835100007 PM 12505246 ER PT J AU Badjatia, N O'Donnell, J Baker, JR Huang, DY Ayata, C Greer, DM McDonald, CT AF Badjatia, N O'Donnell, J Baker, JR Huang, DY Ayata, C Greer, DM McDonald, CT TI Achieving normothermia in febrile subarachnoid hemorrhage patients: Feasibility and safety of a novel intravascular cooling catheter SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 32nd Critical Care Congress CY JAN 28-FEB 02, 2003 CL SAN ANTONIO, TEXAS SP Soc Crit Care Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2002 VL 30 IS 12 SU S MA 18 BP A5 EP A5 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 633RM UT WOS:000180296300018 ER PT J AU Gettings, E Brush, KA AF Gettings, E Brush, KA TI Outcome of postoperative critically ill patients with heparin-induced thrombocytopenia SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 32nd Critical Care Congress CY JAN 28-FEB 02, 2003 CL SAN ANTONIO, TEXAS SP Soc Crit Care Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2002 VL 30 IS 12 SU S MA B BP A160 EP A160 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 633RM UT WOS:000180296300552 ER PT J AU Gettings, E Brush, KA AF Gettings, E Brush, KA TI Outcome of postoperative critically ill patients with heparin-induced, thrombocytopenia SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 32nd Critical Care Congress CY JAN 28-FEB 02, 2003 CL SAN ANTONIO, TEXAS SP Soc Crit Care Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2002 VL 30 IS 12 SU S MA 286 BP A60 EP A60 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 633RM UT WOS:000180296300207 ER PT J AU Iden, CD Lum, N Cooper, JB AF Iden, CD Lum, N Cooper, JB TI Cellular phone interference with medical devices SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 32nd Critical Care Congress CY JAN 28-FEB 02, 2003 CL SAN ANTONIO, TEXAS SP Soc Crit Care Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2002 VL 30 IS 12 SU S MA 201 BP A35 EP A35 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 633RM UT WOS:000180296300123 ER PT J AU Yeung, AS Chang, DF AF Yeung, AS Chang, DF TI Adjustment disorder: Intergenerational conflict in a Chinese immigrant family SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article C1 Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Cambridge, MA 02138 USA. RP Yeung, AS (reprint author), Massachusetts Gen Hosp, Depress & Clin Res Program, 50 Staniford St Suite 401, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PD DEC PY 2002 VL 26 IS 4 BP 509 EP 525 DI 10.1023/A:1021738929069 PG 17 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA 624DU UT WOS:000179745700005 PM 12572771 ER PT J AU Hanninen, VA Pantcheva, MB Freeman, EE Poulin, NR Grosskreutz, CL AF Hanninen, VA Pantcheva, MB Freeman, EE Poulin, NR Grosskreutz, CL TI Activation of caspase 9 in a rat model of experimental glaucoma SO CURRENT EYE RESEARCH LA English DT Article DE apoptosis; caspase; glaucoma; intraocular pressure; retinal ganglion cells ID RETINAL GANGLION-CELLS; ELEVATED INTRAOCULAR-PRESSURE; OPTICAL FRACTIONATOR; DEATH; APOPTOSIS; AXOTOMY; NEURONS; PROTEIN; DAMAGE; NUMBER AB We investigated retinal ganglion cell (RGC) death and activation of caspase 9 in rats with experimental glaucoma. Intraocular pressure (IOP) correlated with surviving RGC. TUNEL-positive RGC were observed in animals with elevated IOP. Procaspase 9 levels increased with IOP intensity. Cleaved caspase 9 was detected by immunoblot only in rats with peak IOP above 35 mmHg for greater than or equal to6 days. Cleaved caspase 9 immunostaining was seen only in the ganglion cell layer of retinas from rats with peak IOP greater than or equal to32 mm Hg. These results support activation of caspase 9, the intrinsic caspase cascade, in RGC death in experimental glaucoma. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Howe Lab Ophthalmol, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Howe Lab Ophthalmol, 243 Charles St, Boston, MA 02114 USA. OI Freeman, Ellen/0000-0002-1403-8427 FU NEI NIH HHS [K11EY00342] NR 22 TC 49 Z9 52 U1 0 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD DEC PY 2002 VL 25 IS 6 BP 389 EP 395 PG 7 WC Ophthalmology SC Ophthalmology GA 690HC UT WOS:000183541500010 PM 12789547 ER PT J AU Stevaux, O Dyson, NJ AF Stevaux, O Dyson, NJ TI A revised picture of the E2F transcriptional network and RB function SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID RETINOBLASTOMA GENE FAMILY; C-ELEGANS; VULVAL DEVELOPMENT; TUMOR-SUPPRESSOR; DNA-REPLICATION; G(1) CONTROL; C/EBP-ALPHA; CELL-DEATH; IN-VIVO; REPRESSION AB New techniques have enhanced our picture of E2F regulation. These studies have shed light on the roles played by individual E2F and retinoblastoma family members and implicate these proteins in processes extending well beyond the G1/S transition. One thorny issue remains: do our current molecular models of E2F and retinoblastoma action explain all of the functions of these proteins in vivo? C1 Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA 02129 USA. RP Stevaux, O (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA64402]; NIGMS NIH HHS [GM53203] NR 53 TC 283 Z9 293 U1 1 U2 4 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 DEC PY 2002 VL 14 IS 6 BP 684 EP 691 DI 10.1016/S0955-0674(02)00388-5 PG 8 WC Cell Biology SC Cell Biology GA 610KD UT WOS:000178958500003 PM 12473340 ER PT J AU Krieser, RJ White, K AF Krieser, RJ White, K TI Engulfment mechanism of apoptotic cells SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID C-ELEGANS; DNASE-II; CAENORHABDITIS-ELEGANS; CORPSE ENGULFMENT; PHAGOCYTOSIS; CLEARANCE; RECEPTOR; DEATH; DROSOPHILA; MACROPINOCYTOSIS AB Apoptotic cells are engulfed and removed by phagocytes. This ensures proper development of the organism and can modulate immune responses. Recent studies have examined molecules on apoptotic cells, such as phosphatidylserine, which may signal for engulfment through multiple receptors. Apoptotic recognition mechanisms may vary with the apoptotic and engulfing cell type, and even with the age of the corpse. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Krieser, RJ (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. RI White, Kristin/D-7936-2013 FU NIGMS NIH HHS [R01 GM069541] NR 35 TC 27 Z9 31 U1 0 U2 0 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 DEC PY 2002 VL 14 IS 6 BP 734 EP 738 DI 10.1016/S0955-0674(02)00390-3 PG 5 WC Cell Biology SC Cell Biology GA 610KD UT WOS:000178958500010 PM 12473347 ER PT J AU Anderson, MS AF Anderson, MS TI Autoimmune endocrine disease SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CLASS-II MOLECULE; GRAVES-DISEASE; THYROTROPIN RECEPTOR; NOD MICE; T-CELLS; ADDISONS-DISEASE; BINDING PROTEIN; REGULATOR AIRE; HUMAN THYMUS; GENE AB The immune system can attack almost any given organ in a very specific and directed fashion. The endocrine system appears to be particularly vulnerable to this kind of insult. Which endocrine organs are most susceptible and why? Genetic studies and animal models have revealed some commonalities for these diseases. The MHC locus appears to help control not only susceptibility to disease but also which endocrine organs are attacked. Autoimmune thymectomy models have revealed suppressor cell populations, which are being intensely sought after as a protective mechanism against endocrine autoimmunity. Finally, the recent cloning of the causative gene for autoimmune polyglandular syndrome type I, called AIRE, has brought central tolerance back into focus as an important mechanism in these endocrine diseases. C1 Harvard Univ, Sch Med, Sect Immunol & Immunogenet, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Anderson, MS (reprint author), Harvard Univ, Sch Med, Sect Immunol & Immunogenet, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [K08-DK59958-01A1] NR 59 TC 19 Z9 20 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2002 VL 14 IS 6 BP 760 EP 764 DI 10.1016/S0952-7915(02)00405-3 PG 5 WC Immunology SC Immunology GA 607VZ UT WOS:000178812600012 PM 12413526 ER PT J AU Turley, SJ AF Turley, SJ TI Dendritic cells: inciting and inhibiting autoimmunity SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID ANTIGEN-PRESENTING CELLS; NONOBESE DIABETIC MICE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CD8(+) T-CELLS; NOD MICE; STEADY-STATE; LYMPH-NODES; TNF-ALPHA; INDUCTION; MATURATION AB Dendritic cells are considered the most influential antigen presenting cells in the body because of their unique role in initiating immunity against threatening antigens. Recent studies addressing the consequences of self-antigen presentation by dendritic cells revealed the unexpected ability of these antigen presenting cells to inhibit T cell-mediated autoimmune diseases. The specific mechanisms by which dendritic cells suppress immune responses have been explored during the past year. These efforts indicate that extrathymic dendritic cells control autoimmunity by inducing peripheral T cell tolerance, a function intimately linked to their state of maturation. C1 Harvard Univ, Sch Med, Dept Immunol & Immunogenet, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Turley, SJ (reprint author), Harvard Univ, Sch Med, Dept Immunol & Immunogenet, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 57 TC 48 Z9 51 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2002 VL 14 IS 6 BP 765 EP 770 DI 10.1016/S0952-7915(02)00399-0 PG 6 WC Immunology SC Immunology GA 607VZ UT WOS:000178812600013 PM 12413527 ER PT J AU Nadler, LM Schultze, JL AF Nadler, LM Schultze, JL TI From genomics to cancer vaccines: Patient-tailored or universal vaccines? SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE cancer vaccines; genomics; proteomics; reverse immunology; tumor immunology ID CYTOTOXIC T-LYMPHOCYTES; TELOMERASE REVERSE-TRANSCRIPTASE; ANTIGEN-PRESENTING CELLS; CD40-ACTIVATED B-CELLS; HUMAN TUMOR-ANTIGENS; CATALYTIC SUBUNIT; MELANOMA PATIENTS; DENDRITIC CELLS; TRANSGENIC MICE; IDENTIFICATION AB There is little doubt about the existence of tumor-associated antigens and T-cell-mediated immune responses against cancer antigens. Antitumor immunity has been identified in many patients with very different types of cancer. Nevertheless, there is still no consensus regarding the correct targets to be used for cancer immunotherapy, including cancer vaccines and adoptive T-cell transfer of tumor antigen-specific T-cells. Certainly, functional genomics and proteomics will have implications on the field of tumor antigen discovery due to the possibility of molecular characterization of whole transcriptomes and proteomes of cancer cells, thereby also identifying potential new targets for cancer immunotherapy. Based on fundamental immunological knowledge, it is hypothesized that the mast promising approach would be patient-tailored. Alternatively, if genes are identified in the majority of all cancers, a more universal approach to cancer vaccines can be envisioned. Success with these opposing strategies will greatly rely on whether it is possible to induce robust immunity against the antigens identified. whether technical and regulatory issues of patient-tailored approaches can be adequately addressed, and certainly also which approach will be economically more advantageous. C1 Dana Farber Canc Inst, Ctr Med Expt, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Cologne, D-5092 Cologne, Germany. ATABIS GmbH, D-50931 Cologne, Germany. RP Nadler, LM (reprint author), Dana Farber Canc Inst, Ctr Med Expt, 44 Binney St, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 45 TC 8 Z9 8 U1 0 U2 2 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD DEC PY 2002 VL 4 IS 6 BP 572 EP 576 PG 5 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 667XN UT WOS:000182260300005 PM 12596359 ER PT J AU Springer, TA AF Springer, TA TI Predicted and experimental structures of integrins and beta-propellers SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID LIGAND-BINDING REGION; AMINO-ACID SEQUENCE; A-DOMAIN; ALPHA-SUBUNIT; CRYSTAL-STRUCTURE; PROTEIN FOLD; HIGH-AFFINITY; EGF-LIKE; HOMOLOGY; FIBRONECTIN AB Integrins and other cell surface receptors have been fertile grounds for structure prediction experiments. Recently determined structures show remarkable successes, especially with beta-propeller domain predictions, and also reveal how ligand binding by integrins is conformationally regulated. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NCI NIH HHS [CA31799]; NHLBI NIH HHS [HL48675] NR 58 TC 26 Z9 27 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD DEC PY 2002 VL 12 IS 6 BP 802 EP 813 DI 10.1016/S0959-440X(02)00384-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 624TH UT WOS:000179777100016 PM 12504686 ER PT J AU Toh, HC Spitzer, TR Preffer, F Alexander, SI McAfee, S Dombkowski, D Clark, JS Colby, C Saidman, S Sackstein, R Sykes, M AF Toh, HC Spitzer, TR Preffer, F Alexander, SI McAfee, S Dombkowski, D Clark, JS Colby, C Saidman, S Sackstein, R Sykes, M TI Fluctuating lymphocyte chimerism, tolerance and anti-tumor response in a patient with refractory lymphoma receiving non-myeloablative conditioning and a haploidentical related allogeneic bone marrow transplant SO CYTOKINES CELLULAR & MOLECULAR THERAPY LA English DT Article DE refractory lymphoma; lymphold chimerism; nonmyeloablative BMT; graft-versus-host; host-versus-graft tolerance ID INDUCTION; THERAPY; CELLS AB A 51-year-old patient with refractory non-Hodgkin lymphoma (NHL) received non-myeloablative conditioning and a two of six (A, B, DR) human leucocyte antigen (HLA) mismatched donor BMT. Post-BMT lymphocytes showed fluctuating T- and natural killer (NK)-cell chimerism, which culminated in mainly donor lymphocytes by Day + 100. Changes in lymphocyte chimerism correlated with anti-donor and anti-host responses in mixed lymphocyte reaction (MLR). On Day + 100, a strong anti-host response was observed in MLR in the absence of graft-versus-host disease (GVHD), together with near complete regression of the patient's lymphoma. A mild chronic GVHD later developed and, eventually, by 680 days post-BMT, the lymphoma had relapsed and MLR reflected a state of global immune unresponsiveness. These observations demonstrate evolving host-versus-graft and graft-versus-host tolerance that correlates with fluctuating lymphoid chimerism and graft-versus-lymphoma (GVL) effects, In the absence of severe GVHD. Eventual lymphoma relapse temporally correlated with a generalised immunosuppressed state. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Bone Marrow Transplant Program, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Dept Surg,Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [R01 CA79986] NR 12 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1368-4736 J9 CYTOKINES CELL MOL T JI Cytokines Cell. Mol. Ther. PD DEC PY 2002 VL 7 IS 2 BP 43 EP 47 DI 10.1080/13684730412331302054 PG 5 WC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Research & Experimental Medicine GA 648PZ UT WOS:000181160900001 PM 12607794 ER PT J AU Nathan, DG AF Nathan, DG TI On clinical research & the future of medicine SO DAEDALUS LA English DT Article C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DAEDALUS PI CAMBRIDGE PA 136 IRVING ST, STE 100, CAMBRIDGE, MA 02138 USA SN 0011-5266 J9 DAEDALUS-US JI Daedalus PD WIN PY 2002 VL 131 IS 1 BP 147 EP 150 PG 4 WC Humanities, Multidisciplinary; Social Sciences, Interdisciplinary SC Arts & Humanities - Other Topics; Social Sciences - Other Topics GA 687MV UT WOS:000183381500016 ER PT J AU Liu, SM Lu, WN Obara, T Kuida, S Lehoczky, J Dewar, K Drummond, IA Beier, DR AF Liu, SM Lu, WN Obara, T Kuida, S Lehoczky, J Dewar, K Drummond, IA Beier, DR TI A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish SO DEVELOPMENT LA English DT Article DE PKD; mouse models; zebrafish; Nek kinase ID MAMMALIAN-CELLS; MODIFYING LOCI; MUTATIONS; GENE; SEVERITY; MICE; DIFFERENTIATION; LOCALIZATION; DROSOPHILA; PROTEIN AB The murine autosomal recessive juvenile cystic kidney (jck) mutation results in polycystic kidney disease. We have identified in jck mice a mutation in Nek8, a novel and highly conserved member of the Nek kinase family. In vitro expression of mutated Nek8 results in enlarged, multinucleated cells with an abnormal actin cytoskeleton. To confirm that a defect in the Nek8 gene can cause cystic disease, we performed a cross-species analysis: injection of zebrafish embryos with a morpholino anti-sense oligonucleotide corresponding to the ortholog of Nek8 resulted in the formation of pronephric cysts. These results demonstrate that comparative analysis of gene function in different model systems represents a powerful means to annotate gene function. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. MIT, Ctr Genome Res, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. RP Beier, DR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK53090, DK4563902, DK54711] NR 38 TC 131 Z9 136 U1 1 U2 7 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 DEC PY 2002 VL 129 IS 24 BP 5839 EP 5846 DI 10.1242/dev.00173 PG 8 WC Developmental Biology SC Developmental Biology GA 631FH UT WOS:000180157100025 PM 12421721 ER PT J AU Brisken, C Ayyannan, A Nguyen, C Heineman, A AF Brisken, C Ayyannan, A Nguyen, C Heineman, A TI IGF-2 is a mediator of prolactin-induced morphogenesis in the breast SO DEVELOPMENTAL CELL LA English DT Article ID MAMMARY-GLAND DEVELOPMENT; FACTOR-II GENE; PROGESTERONE-RECEPTOR; INSULIN-RECEPTOR; TRANSGENIC MICE; CELL-LINES; CYCLIN D1; GROWTH; EXPRESSION; CANCER AB The mechanisms by which prolactin controls proliferation of mammary epithelial cells (MECs) and morphogenesis of the breast epithelium are poorly understood. We show that cyclin D1(-/-) MECs fail to proliferate in response to prolactin and identify IGF-2 as a downstream target of prolactin signaling that lies upstream of cyclin D1 transcription. Ectopic IGF-2 expression restores alveologenesis in prolactin receptor(-/-) epithelium. Alveologenesis is retarded in IGF-2-deficient MECs. IGF-2 and prolactin receptor mRNAs colocalize in the mammary epithelium. Prolactin induces IGF-2 mRNA and IGF-2 induces cyclin D1 protein in primary MECs. Thus, IGF-2 is a mediator of prolactin-induced alveologenesis; prolactin, IGF-2, and cyclin D1, all of which are overexpressed in breast cancers, are components of a developmental pathway in the mammary gland. C1 Harvard Univ, Sch Med, Dept Surg Oncol, Boston, MA 02114 USA. Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA. RP Brisken, C (reprint author), Harvard Univ, Sch Med, Dept Surg Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [5 P01 CA80111]; NICHD NIH HHS [HD 12304, HD 33994] NR 50 TC 123 Z9 123 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD DEC PY 2002 VL 3 IS 6 BP 877 EP 887 DI 10.1016/S1534-5807(02)00365-9 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 624JG UT WOS:000179756100015 PM 12479812 ER PT J AU Green, J AF Green, J TI Morphogen gradients, positional information, and Xenopus: Interplay of theory and experiment SO DEVELOPMENTAL DYNAMICS LA English DT Review DE nodal; activin; embryo; patterning ID VERTEBRATE LIMB DEVELOPMENT; MESODERM-INDUCING FACTOR; NODAL-RELATED GENE; HEPARAN-SULFATE PROTEOGLYCANS; EARLY DROSOPHILA EMBRYO; COMPLETE SECONDARY AXIS; LONG-RANGE ACTION; TGF-BETA FAMILY; SPEMANN ORGANIZER; TWISTED GASTRULATION AB The idea of morphogen gradients has long been an important one in developmental biology. Studies with amphibians and with Xenopus in particular have made significant contributions to demonstrating the existence, identity, and mechanisms of action of morphogens. Mesoderm induction and patterning by activin, nodals, bone morphogenetic proteins, and fibroblast growth factors have been analyzed thoroughly and reveal recurrent and combinatorial roles for these protein growth factor morphogens and their antagonists. The dynamics of nodal-type signaling and the intersection of VegT and beta-catenin intracellular gradients reveal detailed steps in early long-range patterning. Interpretation of gradients requires sophisticated mechanisms for sharpening thresholds, and the activin-Xbra-Gsc system provides an example of this. The understanding of growth factor signal transduction has elucidated growth factor morphogen action and provided tools for dissecting their direct long-range action and distribution. The physical mechanisms of morphogen gradient establishment are the focus of new interest at both the experimental and theoretical level. General themes and emerging trends in morphogen gradient studies are discussed. (C) 2002 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Green, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, 44 Binney St, Boston, MA 02115 USA. RI Green, Jeremy/F-3630-2010 OI Green, Jeremy/0000-0002-6102-2620 NR 214 TC 62 Z9 63 U1 0 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2002 VL 225 IS 4 BP 392 EP 408 DI 10.1002/dvdy.10170 PG 17 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 622FJ UT WOS:000179635700005 PM 12454918 ER PT J AU Rutenberg, J Cheng, SM Levin, M AF Rutenberg, J Cheng, SM Levin, M TI Early embryonic expression of ion channels and pumps in chick and Xenopus development SO DEVELOPMENTAL DYNAMICS LA English DT Review DE ion channels; ion pumps; chick; Xenopus; embryogenesis ID VACUOLAR H+-ATPASE; ENDOGENOUS ELECTRICAL CURRENTS; SODIUM-CALCIUM EXCHANGER; IN-SITU HYBRIDIZATION; GAP JUNCTION CHANNEL; HUMAN BREAST-CANCER; POTASSIUM CHANNEL; PLASMA-MEMBRANE; GENE-EXPRESSION; K+ CHANNEL AB An extensive body of literature implicates endogenous ion currents and standing voltage potential differences in the control of events during embryonic morphogenesis. Although the expression of ion channel and pump genes, which are responsible for ion flux, has been investigated in detail in nervous tissues, little data are available on the distribution and function of specific channels and pumps in early embryogenesis. To provide a necessary basis for the molecular understanding of the role of ion flux in development, we surveyed the expression of ion channel and pump mRNAs, as well as other genes that help to regulate membrane potential. Analysis in two species, chick and Xenopus, shows that several ion channel and pump mRNAs are present in specific and dynamic expression patterns in early embryos, well before the appearance of neurons. Examination of the distribution of maternal mRNAs reveals complex spatiotemporal subcellular localization patterns of transcripts in early blastomeres in Xenopus. Taken together, these data are consistent with an important role for ion flux in early embryonic morphogenesis; this survey characterizes candidate genes and provides information on likely embryonic contexts for their function, setting the stage for functional studies of the morphogenetic roles of ion transport. (C) 2002 Wiley-Liss, Inc. C1 Forsyth Inst, Harvard Forsyth Dept Oral & Dev Biol, Boston, MA 02115 USA. Forsyth Inst, Cytokine Biol Dept, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Forsyth Inst, Harvard Forsyth Dept Oral & Dev Biol, 140 Fenway, Boston, MA 02115 USA. NR 157 TC 17 Z9 17 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2002 VL 225 IS 4 BP 469 EP 484 DI 10.1002/dvdy.10180 PG 16 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 622FJ UT WOS:000179635700011 PM 12454924 ER PT J AU Cheng, SM Chen, I Levin, M AF Cheng, SM Chen, I Levin, M TI K-ATP channel activity is required for hatching in Xenopus embryos SO DEVELOPMENTAL DYNAMICS LA English DT Article DE K-ATP channels; K+ ion; Xenopus; embryogenesis; hatching ID POTASSIUM CHANNELS; EXPRESSION; CELLS; NICORANDIL; RECEPTOR; CURRENTS; OPENERS; GROWTH AB A growing body of work suggests that the activity of ion channels and pumps is an important regulatory factor in embryonic development. We are beginning to identify functional roles for proteins suggested by a survey of expression of ion channel and pump genes in Xenopus and chick embryos (Rutenberg et al. [2002] Dev Dyn 225, this issue). Here, we report that the ATP-sensitive K+ channel protein is present in the hatching gland of Xenopus embryos; moreover, we show that its activity is necessary for hatching in Xenopus. Pharmacologic inhibition of K-ATP channels not only specifically prevents the hatching process but also greatly reduces the endogenous expression of Connexin-30 in the hatching gland. Based on recent work which showed that gap-junctional communication mediated by Cx30 in the hatching gland was required for secretion of the hatching enzyme, we propose that K-ATP channel activity is upstream of Cx30 expression and represents a necessary endogenous step in the hatching of the Xenopus embryo. (C) 2002 Wiley-Liss, Inc. C1 Forsyth Inst, Cytokine Biol Dept, Boston, MA 02115 USA. Harvard Univ, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Forsyth Inst, Cytokine Biol Dept, 140 Fenway, Boston, MA 02115 USA. NR 31 TC 9 Z9 9 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2002 VL 225 IS 4 BP 588 EP 591 DI 10.1002/dvdy.10183 PG 4 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 622FJ UT WOS:000179635700022 PM 12454935 ER PT J AU Klupa, T Warram, JH Antonellis, A Pezzolesi, M Nam, M Malecki, MT Doria, A Rich, SS Krolewski, AS AF Klupa, T Warram, JH Antonellis, A Pezzolesi, M Nam, M Malecki, MT Doria, A Rich, SS Krolewski, AS TI Determinants of the development of diabetes (maturity-onset diabetes of the young-3) in carriers of HNF-1 alpha mutations - Evidence for parent-of-origin effect SO DIABETES CARE LA English DT Article ID HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; I ALPHA-GENE; SUSCEPTIBILITY LOCUS; JAPANESE SUBJECTS; MATERNAL HISTORY; MELLITUS; IDENTIFICATION; MODY3; NIDDM; GLUCOSE AB Objective-To determine the distribution of the age at onset of diabetes (maturity-onset diabetes of the young-3 [MODY3]) and to identify determinants of the onset of diabetes in carriers of HNF-1alpha mutations. Research Design and Methods-Extended families (n=104) with type 2 diabetes inherited in a dominant pattern were recruited and screened for diabetes-causing mutations in HNF-1alpha. Results-HNF-1alpha mutations cosegregated with diabetes in only 13 families, all with a mean age at onset <35 years. Insulin secretion was diminished or absent in mutation carriers (n=101), and diabetes developed in 65% by age 25 years and in 100% by age 50 years. if the mutation was inherited from the mother, diabetes onset was very young in those exposed to diabetes in utero; 57&PLUSMN;8% were affected by age 15 years as compared with 0.0% in those not exposed (P<7x10(-6)). By age 25 years, the difference was reduced (85+/-6 and 55+/-12%, respectively; P=0.02). If the mutation was inherited from the father, diabetes developed in 52+/-8% by age 25 years. Age at diagnosis was shown to be highly heritable (h(2)=0.47, P=0.003). When parent of origin was included in the analyses, the magnitude of genetic contribution increased markedly (h(2)=0.91). Conclusions-Mutations in HNF-1alpha accounts for diabetes in a small proportion of families with a dominant pattern of inheritance. Age at onset of diabetes in MODY3 families varied widely and was influenced by familial factors (including modifying genes) and parent of origin (whether a mutation carrier was exposed to diabetes in utero). C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div,Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. RP Krolewski, AS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div,Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-47475, DK-36836, DK-55523] NR 52 TC 45 Z9 48 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2002 VL 25 IS 12 BP 2292 EP 2301 DI 10.2337/diacare.25.12.2292 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UJ UT WOS:000185504800029 PM 12453976 ER PT J AU Lindeman, N Waltregny, D Signoretti, S Loda, M AF Lindeman, N Waltregny, D Signoretti, S Loda, M TI Gene transcript quantitation by real-time RT-PCR in cells selected by immunohistochemistry-laser capture microdissection SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE immunohistochemistry; PCR; reverse transcription; laser capture microdissection; p27; RNA; quantitative RT-PCR; gene expression ID MESSENGER-RNA ANALYSIS; KINASE INHIBITOR P27; EXPRESSION; DEGRADATION; CARCINOMA; PATTERNS; PICKING; LCM AB Studying tissue-based gene expression in different cell populations often requires immunohistochemistry-guided microdissection. However, mRNA degradation occurs during long staining procedures. We combined a novel rapid immunoperoxidase technique with laser capture microdissection (LCM) and real-time quantitative RT-PCR to compare p27 mRNA expression in prostatic basal/secretory cells. Eight frozen prostate sections were immunostained with antibody 34betaE12 (high-molecular-weight keratin). Secretory and basal cells were separately collected by LCM. p27 transcripts from each cell group were quantitated by real-time RT-PCR, with GAPDH as standard. Immunostaining took 22 minutes, with RNA extraction from similar to40 dissected cells from each compartment initiated within 40 minutes. Qualitative RT-PCR gave a product of the expected size from each sample. Quantitative RT-PCR gave basal/secretory p27/GAPDH ratios of 0.99-16.24 (mean 5.53 +/- 0.643). Immunostaining for keratin 34betaE12 can be done on frozen sections in similar to20 minutes, and mRNA from pure cell populations can be quantitated by RTPCR. We used this technique to show that p27 transcript levels are greater in basal than in secretory prostate cells, suggesting, when combined with prior studies, that regulation of p27 occurs at the protein level in normal cells. This technique may have wide applicability to studies of gene expression in distinct cell populations in heterogeneous tissues. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 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 [R01-CA81755] NR 24 TC 16 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD DEC PY 2002 VL 11 IS 4 BP 187 EP 192 DI 10.1097/00019606-200212000-00001 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 617GE UT WOS:000179353000001 PM 12459634 ER PT J AU Burton, EA Fink, DJ Glorioso, JC AF Burton, EA Fink, DJ Glorioso, JC TI Gene delivery using herpes simplex virus vectors SO DNA AND CELL BIOLOGY LA English DT Review ID LATENCY-ASSOCIATED TRANSCRIPT; TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; CELL-SURFACE RECEPTORS; HOST SHUTOFF FUNCTION; RAT SPINAL-CORD; HEPARAN-SULFATE PROTEOGLYCANS; VESICULAR STOMATITIS-VIRUS; HUMAN TRIGEMINAL GANGLIA; IMMEDIATE-EARLY PROTEINS AB Herpes simplex virus (HSV) is a neurotropic DNA virus with many favorable properties as a gene delivery vector. HSV is highly infectious, so HSV vectors are efficient vehicles for the delivery of exogenous genetic material to cells. Viral replication is readily disrupted by null mutations in immediate early genes that in vitro can be complemented in trans, enabling straightforward production of high-titre pure preparations of nonpathogenic vector. The genome is large (152 Kb) and many of the viral genes are dispensable for replication in vitro, allowing their replacement with large or multiple transgenes. Latent infection with wild-type virus results in episomal viral persistence in sensory neuronal nuclei for the duration of the host lifetime. Transduction with replication-defective vectors causes a latent-like infection in both neural and non-neural tissue; the vectors are non-pathogenic, unable to reactivate and persist long-term. The latency active promoter complex can be exploited in vector design to achieve long-term stable transgene expression in the nervous system. HSV vectors transduce a broad range of tissues because of the wide expression pattern of the cellular receptors recognized by the virus. Increasing understanding of the processes involved in cellular entry has allowed preliminary steps to be taken towards targeting the tropism of HSV vectors. Using replication-defective HSV vectors, highly encouraging results have emerged from recent pre-clinical studies on models of neurological disease, including glioma, peripheral neuropathy, chronic pain and neurodegeneration. Consequently, HSV vectors encoding appropriate transgenes to tackle these pathogenic processes are poised to enter clinical trials. C1 Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Oxford, Dept Clin Neurol, Oxford OX1 2JD, England. VA Pittsburgh Healthcare Syst, CRECC, Pittsburgh, PA USA. RP Glorioso, JC (reprint author), Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, E1240 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15261 USA. OI Burton, Edward/0000-0002-8072-4636 NR 236 TC 55 Z9 55 U1 1 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD DEC PY 2002 VL 21 IS 12 BP 915 EP 936 DI 10.1089/104454902762053864 PG 22 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 632NR UT WOS:000180229900006 PM 12573050 ER PT J AU Schlozman, SC AF Schlozman, SC TI The shrink in the classroom - To view or not to view SO EDUCATIONAL LEADERSHIP LA English DT Editorial Material ID MEDIA; ADOLESCENTS; VIOLENCE; TELEVISION; IMPACT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Schlozman, SC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD DEC-JAN PY 2002 VL 60 IS 4 BP 87 EP 88 PG 2 WC Education & Educational Research SC Education & Educational Research GA 621CY UT WOS:000179572000020 ER PT J AU Brown, SM Benneyan, JC Theobald, DA Sands, K Hahn, MT Potter-Bynoe, GA Stelling, JM O'Brien, TF Goldmann, DA AF Brown, SM Benneyan, JC Theobald, DA Sands, K Hahn, MT Potter-Bynoe, GA Stelling, JM O'Brien, TF Goldmann, DA TI Binary cumulative sums and moving averages in nosocomial infection cluster detection SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 25-28, 2001 CL SAN FRANCISCO, CALIFORNIA SP Infect Dis Soc Amer ID HOSPITALIZED-PATIENTS; SURVEILLANCE DATA; DISEASE CLUSTERS; ADVERSE EVENTS; CUSUM; COMPETENCE; OUTBREAKS AB Clusters of nosocomial infection often occur undetected, at substantial cost to the medical system and individual patients. We evaluated binary cumulative sum (CUSUM) and moving average (MA) control charts for automated detection of nosocomial clusters. We selected two outbreaks with genotyped strains and used resistance as inputs to the control charts. We identified design parameters for the CUSUM and MA (window size, k, a, b, p(0), p(1)) that detected both outbreaks, then calculated an associated positive predictive value (PPV) and time until detection (TUD) for sensitive charts. For CUSUM, optimal performance (high PPV, low TUD, fully sensitive) was for 0.1 less than or equal to alpha less than or equal to0.25 and 0.2 less than or equal to beta less than or equal to0.25, with p(0) = 0.05, with a mean TUD of 20 (range 8-43) isolates. Mean PPV was 96.5% (relaxed criteria) to 82.6% (strict criteria). MAs had a mean PPV of 88.5% (relaxed criteria) to 46.1% (strict criteria). CUSUM and MA may be useful techniques for automated surveillance of resistant infections. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northeastern Univ, Boston, MA 02115 USA. Vecna Technol Inc, Hyattsville, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. WHO, Collaborat Ctr Antimicrobial Resistance Surveilla, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Brown, SM (reprint author), 527 Leverett Mail Ctr, Cambridge, MA 02138 USA. RI Brown, Samuel/E-6846-2015 OI Brown, Samuel/0000-0003-1206-6261 FU NIAID NIH HHS [1 R43 AI48332-01] NR 34 TC 19 Z9 20 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2002 VL 8 IS 12 BP 1426 EP 1432 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 625UQ UT WOS:000179834300011 PM 12498659 ER PT J AU Kulkarni, RN Okada, T AF Kulkarni, RN Okada, T TI Tissue-specific targeting of the insulin receptor gene SO ENDOCRINE LA English DT Review DE Cre/lox; insulin receptor; islet beta-cells; brain; knockout ID GROWTH-FACTOR-I; PANCREATIC BETA-CELLS; IMPAIRED GLUCOSE-TOLERANCE; TYPE-1 IGF RECEPTOR; TRANSGENIC MICE; DIABETES-MELLITUS; ADIPOSE-TISSUE; PHOSPHOINOSITIDE 3-KINASE; MESSENGER-RNA; KNOCKOUT MICE AB The techniques to study the mechanisms that underlie the pathogenesis of disease processes have been revolutionized by the development of methods that allow spatiotemporal control of gene deletion or gene expression in transgenic and knockout animals. The ability to interfere with the function of a single protein in a specific tissue allows unprecedented flexibility for exploring gene function in both health and disease. The present review will summarize some of the different knockouts and transgenics generated recently to study type 2 diabetes and critically evaluate the techniques used to examine the function of the insulin receptor in two nonclassical insulin target tissues-the pancreatic islet and the central nervous system. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Rm 602,1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 02885] NR 122 TC 3 Z9 3 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD DEC PY 2002 VL 19 IS 3 BP 257 EP 266 DI 10.1385/ENDO:19:3:257 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652DB UT WOS:000181363600006 PM 12624425 ER PT J AU Shimizu, S Maegawa, H Egawa, K Shi, K Bryer-Ash, M Kashiwagi, A AF Shimizu, S Maegawa, H Egawa, K Shi, K Bryer-Ash, M Kashiwagi, A TI Mechanism for differential effect of protein-tyrosine phosphatase 1B on Akt versus mitogen-activated protein kinase in 3T3-L1 adipocytes SO ENDOCRINOLOGY LA English DT Article ID INSULIN SENSITIVITY; RESISTANCE; OBESITY; OVEREXPRESSION; RECEPTOR; TISSUE; PTP-1B; MICE AB We investigated the effect of overexpression of protein-tyrosine phosphatase 1B (PTP1B) on insulin signaling in 3T3-L1 adipocytes. Overexpression of a wild-type PTP1B in L1 adipocytes as well as in L6 myocytes, led to a profound decrease in insulin-stimulated phosphorylation of MAPK. Even though the decrease in insulin receptor substrate protein-1 (IRS-1) phosphorylation was identical with that seen in L6 myocytes, overexpression of wild-type PTP1B in L1 adipocytes was associated with modest impairment of insulin-stimulated AM phosphorylation in addition to a small, but significant, attenuation in insulin-stimulated glucose uptake, when compared with a phosphatase-negative mutant. Regarding the relatively small effect on Akt phosphorylation, we obtained identical results in rat 1 fibroblasts overexpressing human insulin receptor, suggesting that the higher expression levels of insulin receptor and IRS-1 might be responsible. With regard to the large effect on MAPK phosphorylation, we found that PTP1B overexpression led to the impaired phosphorylation of both IRS-1 and Shc, resulting in a decrease in their association with Grb2. Furthermore, phosphorylation of Shc stimulated by platelet-derived growth factor was also attenuated, without any change in its receptors, suggesting that PTP1B directly regulates Shc phosphorylation. These data demonstrate that PTP1B negatively regulates insulin signaling in the MAPK cascade to a much greater extent than the Akt pathway in some cell lines, especially in L1 adipocytes. C1 Shiga Univ Med Sci, Dept Med, Div Endocrinol & Metab, Shiga 5202192, Japan. Univ Calif Los Angeles, Dept Med, Div Endocrinol Diabet & Hypertens, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90095 USA. RP Maegawa, H (reprint author), Shiga Univ Med Sci, Dept Med, Div Endocrinol & Metab, Shiga 5202192, Japan. NR 23 TC 19 Z9 19 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2002 VL 143 IS 12 BP 4563 EP 4569 DI 10.1210/en.2002-220517 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 620QK UT WOS:000179543900011 PM 12446583 ER PT J AU Zhang, SL Chen, X Wei, CC Filep, JG Tang, SS Ingelfinger, JR Chan, JSD AF Zhang, SL Chen, X Wei, CC Filep, JG Tang, SS Ingelfinger, JR Chan, JSD TI Insulin inhibits dexamethasone effect on angiotensinogen gene expression and induction of hypertrophy in rat kidney proximal tubular cells in high glucose SO ENDOCRINOLOGY LA English DT Article ID ELEMENT-BINDING PROTEIN; CAMP RESPONSE ELEMENT; MESSENGER-RNA; CELLULAR HYPERTROPHY; KINASE PATHWAY; II RECEPTOR; RENIN; BETA; STIMULATE; BLOCKADE AB The present studies investigated whether insulin inhibits the stimulatory effect of dexamethasone (DEX) on angiotensinogen (ANG) gene expression and induction of hypertrophy in rat immortalized renal proximal tubular cells (IRPTCs) in a high-glucose milieu. Rat IRPTCs were cultured in monolayer. ANG and ANG mRNA expression in IRPTCs were quantified by a specific RIA for rat ANG and by RT-PCR assay, respectively. A fusion gene containing the full length of the 5'-flanking region of the rat ANG gene linked to a chloramphenicol acetyl transferase reporter gene was introduced into IRPTCs. The level of fusion gene expression was determined by cellular chloramphenicol acetyl transferase enzymatic activity: Cellular hypertrophy was assessed by flow cytometry, cellular p27(Kip1) protein expression, and protein assay. Our results showed that high glucose (i.e. 25 mM) and DEX (10(-7) M) additively stimulated ANG gene expression and induced IRPTC hypertrophy. Insulin inhibited the effect of high glucose and DEX on these parameters. The inhibitory effect of insulin was reversed by PD 98059 (a MAPK inhibitor) but not by wortmannin (a phosphatidylinositol-3-kinase inhibitor). These results demonstrate that insulin is effective in blocking the stimulatory action of high glucose and DEX on ANG gene expression and induction of IRPTC hypertrophy, suggesting its important role in preventing local intrarenal renin-angiotensin system activation and renal proximal tubular cell hypertrophy induced by hyperglycemia and glucocorticoids in vivo. C1 Univ Montreal, Ctr Hosp, Hotel Dieu Hosp, Res Ctr, Montreal, PQ H2W 1T8, Canada. Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Chan, JSD (reprint author), Univ Montreal, Ctr Hosp, Hotel Dieu Hosp, Res Ctr, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. FU NHLBI NIH HHS [HL-48455]; NIDDK NIH HHS [DK-50836] NR 51 TC 21 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2002 VL 143 IS 12 BP 4627 EP 4635 DI 10.1210/en.2002-220408 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 620QK UT WOS:000179543900018 PM 12446590 ER PT J AU Claeskens, G Aerts, M Molenberghs, G Ryan, L AF Claeskens, G Aerts, M Molenberghs, G Ryan, L TI Robust benchmark dose determination based on profile score methods SO ENVIRONMENTAL AND ECOLOGICAL STATISTICS LA English DT Article DE clustered binary data; generalized estimating equations; likelihood ratio; profile likelihood; score statistic; toxicology ID CLUSTERED BINARY DATA; QUANTITATIVE RISK ASSESSMENT; LONGITUDINAL DATA-ANALYSIS; GENERALIZED LINEAR-MODELS; DEVELOPMENTAL TOXICITY; LIKELIHOOD; TESTS; MISSPECIFICATION; OUTCOMES AB We investigate several methods commonly used to obtain a benchmark dose and show that those based on full likelihood or profile likelihood methods might have severe shortcomings. We propose two new profile likelihood-based approaches which overcome these problems. Another contribution is the extension of the benchmark dose determination to non full likelihood models, such as quasi-likelihood, generalized estimating equations, which are widely used in settings such as developmental toxicity where clustered data are encountered. This widening of the scope of application is possible by the use of (robust) score statistics. Benchmark dose methods are applied to a data set from a developmental toxicity study. C1 Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. Limburgs Univ Ctr, Ctr Stat, B-3590 Diepenbeek, Belgium. Harvard Sch Publ Hlth, Boston, MA 02155 USA. Dana Farber Canc Inst, Boston, MA 02155 USA. RP Claeskens, G (reprint author), Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 31 TC 1 Z9 1 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1352-8505 J9 ENVIRON ECOL STAT JI Environ. Ecol. Stat. PD DEC PY 2002 VL 9 IS 4 BP 357 EP 377 DI 10.1023/A:1020962622829 PG 21 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 612TD UT WOS:000179090800003 ER PT J AU Kohane, TS Holmes, TL Chau, Y Zurakowski, D Langer, T Cha, TH AF Kohane, TS Holmes, TL Chau, Y Zurakowski, D Langer, T Cha, TH TI Effectiveness of muscimol-containing microparticles against pilocarpine-induced focal seizures SO EPILEPSIA LA English DT Article ID DRUG-DELIVERY; EPILEPSY; RATS; EPILEPTOGENESIS; PARTICLES; SYSTEM; MODEL AB Purpose: To investigate the efficacy of in situ lipid-protein-sugar particles (LPSPs) in mitigating the epileptogenic and histologic effects of intrahippocampal pilocarpine in rats. Methods: LPSPs with and without muscimol were produced by spray-drying, sized by Coulter counter, and muscimol content determined by high-pressure liquid chromatography (HLPC). Particles, free muscimol or saline, were injected into the hippocampi of Sprague-Dawley rats before 40 mM pilocarpine, and seizure activity was scored. The trajectories of behavioral scores between groups were compared with two-way repeated measures analysis of variance. Animals were killed after 2 weeks. Brain sections were stained (Timm and thionin) and scored. Results: LPSPs were 4 to 5 mum in diameter, and contained 0 or 2% (wt/wt) muscimol. In vitro, muscimol was released over a 5-day period. Intrahippocampal injections of normal saline and blank LPSPs did not deter seizure activity from pilocarpine. The rise of the trajectory in behavior scores in animals given LPSPs containing 5 mug muscimol was significantly slower than in those receiving saline, blank particles, or 5 mug of unencapsulated muscimol. There was less apparent neuronal injury and CA3 and supragranular mossy fiber sprouting in hippocampi of animals receiving Tuscimol-containing particles than in animals that did not receive muscimol. Hippocampi of animals that received 5 mug of encapsulated muscimol showed less supragranular sprouting than did those receiving 5 mug of unencapsulated muscimol, but showed no difference in cell loss or CA3 sprouting. Conclusions: Focally delivered biodegradable microparticles loaded with muscimol are effective in reducing seizure activity from pilocarpine in animals and mitigate the histologic effects. C1 Massachusetts Gen Hosp Children, Pediat Intens Care Unit, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Kohane, TS (reprint author), Massachusetts Gen Hosp, Pediat Intens Care Unit, Ellison 317,55 Fruit St, Boston, MA 02115 USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD DEC PY 2002 VL 43 IS 12 BP 1462 EP 1468 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 623DU UT WOS:000179688700003 ER PT J AU Cole, AJ AF Cole, AJ TI Evaluation and treatment of epilepsy in multiply handicapped individuals SO EPILEPSY & BEHAVIOR LA English DT Article DE epilepsy; mental retardation; developmental; perinatal; multiply handicapped; genetic; trauma; diagnosis ID BRAIN INJURY; SEIZURES AB The evaluation and treatment of patients with seizures and multiple handicaps are challenging. An orderly approach to these patients, however, can be especially rewarding. As in other patient populations, evaluation rests on the clinical cornerstones of history, examination, imaging, and electroencephalography. Several disease entities are overrepresented in the multiply handicapped population. Here, we review the principles of evaluation and some of the most common etiologies of recurrent seizures afflicting handicapped individuals. Practical issues that arise in institutional settings are highlighted, and basic treatment principles are discussed. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. NR 10 TC 3 Z9 3 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2002 VL 3 IS 6 SU S BP S2 EP S6 AR PII S1525-5050(02)00535-8 PN 2 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 703XK UT WOS:000184307500002 ER PT J AU Garraway, LA Chabner, B AF Garraway, LA Chabner, B TI MDRI inhibition: less resistance or less relevance? SO EUROPEAN JOURNAL OF CANCER LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; SOUTHWEST-ONCOLOGY-GROUP; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; DRUG-RESISTANCE; IN-VIVO; CYCLOSPORINE; CANCER; MODULATION; ETOPOSIDE C1 Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Chabner, B (reprint author), Massachusetts Gen Hosp, Dept Med Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. NR 27 TC 14 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 2002 VL 38 IS 18 BP 2337 EP 2340 AR PII S0959-8049(02)00490-2 DI 10.1016/S0959-8049(02)00490-2 PG 4 WC Oncology SC Oncology GA 630FZ UT WOS:000180098000006 PM 12460776 ER PT J AU Hasan, M Polic, B Bralic, M Jonjic, S Rajewsky, K AF Hasan, M Polic, B Bralic, M Jonjic, S Rajewsky, K TI Incomplete block of B cell development and immunoglobulin production in mice carrying the mu MT mutation on the BALB/c background SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE mu chain; immunoglobulin; isotype switch; plasma cell; immune response ID BONE-MARROW; TARGETED DISRUPTION; MEMBRANE EXON; LIGHT-CHAIN; GENE; SELECTION; MOUSE; LYMPHOCYTES; REPERTOIRE; ANTIBODY AB The expression of the preB cell receptor (preBCR), composed of the R chain, surrogate light chains and the Igalpha/Igbeta signal transduction unit, permits further differentiation of B cell precursors. C57BL/6 mice homozygous for an inactivating mutation of the membrane exon of the mu chain gene (C57BL/6(mumT/mumT)) cannot form a preBCR and are, consequently, devoid of mature B lymphocytes. Here we present evidence that the block of B cell development by the muMT mutation is incomplete in BALB/c mice. Unlike C57BL/6(muMT/muMT), BALB/c(muMT/muMT) mice generate small numbers of mature B cells, accumulate plasma cells and produce high levels of all immunoglobulin isotypes, except IgM. The observed phenomenon seems to be controlled by a single genetic locus that is not linked to IgH. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Rijeka, Fac Med, Dept Histol & Embryol, Rijeka, Croatia. Univ Cologne, Inst Genet, Dept Immunol, D-5000 Cologne, Germany. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Polic, Bojan/B-8622-2014 OI Polic, Bojan/0000-0003-3930-9630 NR 34 TC 50 Z9 50 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2002 VL 32 IS 12 BP 3463 EP 3471 DI 10.1002/1521-4141(200212)32:12<3463::AID-IMMU3463>3.0.CO;2-B PG 9 WC Immunology SC Immunology GA 627AY UT WOS:000179907000014 PM 12442328 ER PT J AU Manetta, J Franz, LH Moon, C Perell, KL Fang, MK AF Manetta, J Franz, LH Moon, C Perell, KL Fang, MK TI Comparison of hip and knee muscle moments in subjects with and without knee pain SO GAIT & POSTURE LA English DT Article DE gait; osteoarthritis; kinetics ID OSTEO-ARTHRITIS; NHANES-I; OSTEOARTHRITIS; GAIT; OBESITY; DISEASE; AGE AB Elderly subjects with and without knee pain walked at a comfortable pace during gait analysis. Comparison of peak hip and knee internal extensor generalized muscle moments (GMMs) during loading response was made between groups. Walking velocity, peak hip internal extensor GMM, and knee range of motion (ROM) were significantly less for the group with knee pain than for the group without pain. Peak hip internal extensor GMM was strongly correlated with velocity, but peak knee internal extensor GMM was not. Knee ROM limitations may account for the increased peak knee internal extensor GMM in the knee pain group. (C) 2002 Published by Elsevier Science B.V. C1 Mt St Marys Coll, Dept Phys Therapy, Los Angeles, CA 90049 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Perell, KL (reprint author), VA Greater Los Angeles Healthcare Syst, Phys Med & Rehabil Dept 117, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 22 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD DEC PY 2002 VL 16 IS 3 BP 249 EP 254 AR PII S0966-6362(02)00009-7 DI 10.1016/S0966-6362(02)00009-7 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 630RR UT WOS:000180123100004 PM 12443949 ER PT J AU Hwang, IR Kodama, T Kikuchi, S Sakai, K Peterson, LE Graham, DY Yamaoka, Y AF Hwang, IR Kodama, T Kikuchi, S Sakai, K Peterson, LE Graham, DY Yamaoka, Y TI Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1 beta production in Helicobacter pylori infection SO GASTROENTEROLOGY LA English DT Article ID RECEPTOR ANTAGONIST GENE; NECROSIS-FACTOR-ALPHA; ACID-SECRETION; INCREASED RISK; PLASMA-LEVELS; IL-1RA GENE; IL-1-BETA; CANCER; ASSOCIATION; DISEASE AB Background & Aims: Although epidemiological studies suggest that interleukin (IL)-1 genetic polymorphisms are involved in Helicobacter pylori-related gastric carcinogenesis, the data are conflicting regarding the effects of these polymorphisms on IL-1beta production. Methods: IL-1B-511 polymorphism was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and IL-1RN variable number of tandem repeats was determined by PCR. Mucosal IL-1beta levels were measured by enzyme-linked immunosorbent assay. To determine which factors influence mucosal IL-1beta levels, gastric inflammation, and atrophy, multiple regression analyses were performed. Results: We studied 117 H. pylori-infected Japanese patients. Carriers of the IL-1B-511T/T genotype or IL-1RN*2 allele had higher mucosal IL-1beta levels than noncarriers (partial regression coefficient [PRC] SE), TT versus CC: 37.6 +/- 6 [antrum] and 32.1 +/- 6 [corpus] pg/mg protein (P < 0.001 for each), *1/*2 versus *1/*1: 24 < 8 [antrum] (P < 0.01) and 36.5 +/- 7 [corpus] (P < 0.001). Simultaneous carriers of IL-1B-511T/T genotype and IL-1RN*2 allele had the highest IL-1(3 levels (82.9 +/- 12 [antrum] and 87.2 +/- 11 [corpus]) and showed a synergistic effect between 2 loci. The *1/*2 carriers were closely related to atrophy (PRC SE; 0.87 +/- 0.4 [antrum] and 0.93 +/- 0.4 [corpus], P < 0.05), whereas being a carrier of the -511T/T genotype was related to severe gastric inflammation. Conclusions: IL-1 genetic polymorphisms influenced H. pylori-related gastric mucosal IL-1beta levels and were related to gastric inflammation and atrophy, factors thought to be important in gastric carcinogenesis. C1 Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Kyoto Prefectural Univ Med, Dept Internal Med 3, Kyoto 602, Japan. Aichi Med Univ, Sch Med, Dept Publ Hlth, Aichi, Japan. Baylor Coll Med, Dept Med Mol & Human Genet, Houston, TX 77030 USA. RP Yamaoka, Y (reprint author), Vet Affairs Med Ctr 111D, Room 3A-320,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [DK-53659, DK56338] NR 48 TC 241 Z9 265 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2002 VL 123 IS 6 BP 1793 EP 1803 DI 10.1053/gast.2002.37043 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 620RA UT WOS:000179545300010 PM 12454835 ER PT J AU Leitzmann, MF Stampfer, MJ Willett, WC Spiegelman, D Colditz, GA Giovannucci, EL AF Leitzmann, MF Stampfer, MJ Willett, WC Spiegelman, D Colditz, GA Giovannucci, EL TI Coffee intake is associated with lower risk of symptomatic gallstone disease in women SO GASTROENTEROLOGY LA English DT Article ID GALLBLADDER-DISEASE; CHOLESTEROL-METABOLISM; LIPID-PEROXIDATION; NONULCER DYSPEPSIA; PHYSICAL-ACTIVITY; CYCLIC-AMP; CAFFEINE; CONSUMPTION; SMOKING; WEIGHT AB Background & Aims: Metabolic studies have shown that coffee affects several hepatobiliary processes that are involved in cholesterol lithogenesis. We previously showed that coffee drinking was associated with a lower risk of symptomatic gallstone disease in men. Methods: We prospectively examined the association between coffee drinking and cholecystectomy, a surrogate of symptomatic gallstone disease, in a cohort of. 80,898 women age 34-59 years in 1980 who had no history of gallstone disease. Coffee consumption and cholecystectomy were reported by participants on biennial mailed questionnaires. Results: During 20 years of follow-up to the year 2000, 7,811 women reported a cholecystectomy. Compared with women who consistently reported consuming no caffeinated coffee, the multivariate relative risks (adjusting for risk factors for gallstone disease) of cholecystectomy comparing increasing categories of consistent intake of caffeinated coffee (0, 1, 2-3, and greater than or equal to4 cups/day) were 1.0, 0.91, 0.78, and 0.72 (95% confidence interval comparing extreme categories, 0.62-0.84; P value of test for trend < 0.0001). Caffeine intake from beverages and dietary sources was also inversely associated with risk of cholecystectomy. The multivariate relative risks comparing increasing categories of caffeine intake (less than or equal to25, 26-100, 101-200, 201-400, 401-800, and >800 mg/day) were 1.0, 1.03, 1.01, 0.94, 0.85, and 0.85 (95% confidence interval comparing extreme categories, 0.74-0.96; P value of test for trend <0.0001). In contrast, decaffeinated coffee was not associated with risk. Conclusions: These data suggest that consumption of caffeinated coffee may play a role in the prevention of symptomatic gallstone disease in women. C1 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 Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Ctr, Program Epidemiol, Boston, MA 02115 USA. RP Leitzmann, MF (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Pl S,Room 3028, Rockville, MD 20852 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [5T32 CA09001-26, CA 87969]; NIDDK NIH HHS [DK 46200] NR 49 TC 46 Z9 47 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2002 VL 123 IS 6 BP 1823 EP 1830 DI 10.1053/gast.2002.37054 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 620RA UT WOS:000179545300013 PM 12454839 ER PT J AU Ko, CW Lee, SP AF Ko, CW Lee, SP TI Epidemiology and natural history of common bile duct stones and prediction of disease SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT NIH State-of-the-Science Conference - ERCP for Diagnosis and Therapy CY JAN 14-16, 2002 CL BETHESDA, MARYLAND ID GALLSTONE FORMATION; GALLBLADDER-DISEASE; MR CHOLANGIOGRAPHY; PHYSICAL-ACTIVITY; CHOLESTEROL; CHOLECYSTECTOMY; CHOLELITHIASIS; RISK; CHOLEDOCHOLITHIASIS; WOMEN C1 Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. RP Lee, SP (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. NR 41 TC 34 Z9 40 U1 0 U2 4 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 DEC PY 2002 VL 56 IS 6 SU S BP S165 EP S169 DI 10.1067/mge.2002.129005 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 623WN UT WOS:000179726000005 PM 12447261 ER PT J AU Perell, KL AF Perell, KL TI Assessing the risk of falls: Guidelines for selecting appropriate measures for clinical practice settings SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID ELDERLY PATIENTS; FUNCTIONAL ASSESSMENT; PREVENTION; PROBABILITY; POPULATION; MOBILITY; INDEX; GAIT; GO C1 Calif State Univ Fullerton, Div Kinesiol & Hlth Promot, Fullerton, CA 92634 USA. VA Greater Los Angeles Healthcare Syst, Dept Med Phys, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Rehabil & Res, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Phys Med & Rehabil, Los Angeles, CA 90024 USA. RP Perell, KL (reprint author), Calif State Univ Fullerton, Div Kinesiol & Hlth Promot, Fullerton, CA 92634 USA. NR 19 TC 0 Z9 0 U1 2 U2 3 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD WIN PY 2002 VL 26 IS 4 BP 66 EP 68 PG 3 WC Gerontology SC Geriatrics & Gerontology GA 725AN UT WOS:000185520600013 ER PT J AU Kercher, BJ Rubenstein, LZ AF Kercher, BJ Rubenstein, LZ TI Home-safety checklists for elders in print and on the Internet SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article C1 Los Angeles Cty Dept Hlth Serv, Los Angeles, CA 90012 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. RP Kercher, BJ (reprint author), Los Angeles Cty Dept Hlth Serv, Los Angeles, CA 90012 USA. NR 5 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD WIN PY 2002 VL 26 IS 4 BP 69 EP 74 PG 6 WC Gerontology SC Geriatrics & Gerontology GA 725AN UT WOS:000185520600014 ER PT J AU Baena, A Leung, JY Sullivan, AD Landires, I Vasquez-Luna, N Quinones-Berrocal, J Fraser, PA Uko, GP Delgado, JC Clavijo, OP Thim, S Meshnick, SR Nyirenda, T Yunis, EJ Goldfeld, AE AF Baena, A Leung, JY Sullivan, AD Landires, I Vasquez-Luna, N Quinones-Berrocal, J Fraser, PA Uko, GP Delgado, JC Clavijo, OP Thim, S Meshnick, SR Nyirenda, T Yunis, EJ Goldfeld, AE TI TNF-alpha promoter single nucleotide polymorphisms are markers of human ancestry SO GENES AND IMMUNITY LA English DT Article DE SNP; haplotype; HLA; evolution; cytokine; gene regulation ID HLA HAPLOTYPES; GENE PROMOTER; POPULATION; REGION; IDENTIFICATION; ALLELES AB We present a map of single nucleotide polymorphisms (SNPs) in the human tumor necrosis factor (TNF)-alpha promoter based upon exploratory sequencing of 333 human TNF-alpha gene promoters from individuals of distinct ancestral backgrounds. We detect 10 TNF-alpha promoter SNPs that occur with distinct frequencies in populations of different ancestry. Consistent with these findings, we show that two TNF-alpha SNPs, the -243 SNP and the -856 SNP, are the first SNP markers of a sub-Saharan African-derived extended haplotype and an Amerindian HLA haplotype, respectively. Comparisons of TNF-alpha promoter SNP allele frequencies can thus help elucidate variation of HLA haplotypes and their distribution among existing ethnic groups and shed light into the history of human populations. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Mangochi, Dist Hosp, Dept Community Hlth, Mangochi, Malawi. Cambodian Hlth Comm, Phnom Pehn, Cambodia. Hosp Antonio Lorena, Cuzco, Peru. Dana Farber Canc Inst, Div Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Yunis, EJ (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL59838]; NIGMS NIH HHS [GM-56492] NR 28 TC 48 Z9 52 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD DEC PY 2002 VL 3 IS 8 BP 482 EP 487 DI 10.1038/sj.gene.6363898 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 631RP UT WOS:000180180800006 PM 12486607 ER PT J AU Yahata, T Takedatsu, H Dunwoodie, SL Braganca, J Swingler, T Withington, SL Hur, J Coser, KR Isselbacher, KJ Bhattacharya, S Shioda, T AF Yahata, T Takedatsu, H Dunwoodie, SL Braganca, J Swingler, T Withington, SL Hur, J Coser, KR Isselbacher, KJ Bhattacharya, S Shioda, T TI Cloning of mouse cited4, a member of the CITED family p300/CBP-binding transcriptional coactivators: Induced expression in mammary epithelial cells SO GENOMICS LA English DT Article DE transcriptional coactivator; mammary gland ID MELANOCYTE-SPECIFIC GENE; BINDING-PROTEIN; NUCLEAR-PROTEIN; MSG1; MRG1; DIFFERENTIATION; TRANSFORMATION; TRANSACTIVATOR; SURVIVAL; HOMOLOG AB The CITED family proteins bind to CBP/p300 transcriptional integrators through their conserved C-terminal acidic domain and function as coactivators. The 21-kDa mouse Cited4 protein, a novel member of the CITED family, interacted with CBP/p300 as well as isoforms of the TFAP2 transcription factor, coactivating TFAP2-dependent transcription. The cited4 gene consisted of only a single exon located on chromosome 4 at 56.5-56.8 cM flanked by marker genes kcnq4 and scml1. Expression of Cited4 protein was strong and selective in embryonic hematopoietic tissues and endothelial cells. In adult animals, Cited4 showed strong milk cycle-dependent induction in pregnant and lactating mammary epithelial cells. Strong induction of Cited4 expression was also observed in SCp2 mouse mammary epithelial cells during their prolactin-dependent in vitro differentiation. These results implied possible roles for Cited4 in regulation of gene expression during development and differentiation of blood cells, endothelial cells, and mammary epithelial cells. C1 Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Charlestown, MA 02129 USA. Victor Chang Cardiac Res Inst, Dev Biol Unit, Sydney, NSW 2010, Australia. Univ New S Wales, Dept Biotechnol & Biomol Sci, Kensington, NSW 2010, Australia. Univ Oxford, Dept Cardiovasc Med, Oxford OX3 7BN, England. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Bldg 149,7th Floor,13th St, Charlestown, MA 02129 USA. RI Bhattacharya, Shoumo/F-4127-2010; Braganca, Jose/F-4410-2012; OI Braganca, Jose/0000-0001-9566-400X; Dunwoodie, Sally/0000-0002-2069-7349 FU NCI NIH HHS [R01-CA82230] NR 36 TC 21 Z9 27 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 2002 VL 80 IS 6 BP 601 EP 613 DI 10.1006/geno.2002.7005 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 628FH UT WOS:000179981600007 PM 12504852 ER PT J AU Pearsall, N Bhattacharya, G Wisecarver, J Adams, J Cosgrove, D Kimberling, W AF Pearsall, N Bhattacharya, G Wisecarver, J Adams, J Cosgrove, D Kimberling, W TI Usherin expression is highly conserved in mouse and human tissues SO HEARING RESEARCH LA English DT Article ID SYNDROME TYPE IIA; IV COLLAGEN; BASEMENT-MEMBRANE; GENE; LOCALIZATION; ALPHA-3(IV); PREVALENCE; MUTATIONS; 1Q41 AB Usher syndrome is an autosomal recessive disease that results in varying degrees of hearing loss and retinitis pigmentosa. Three types of Usher syndrome (1, 11, and 111) have been identified clinically with Usher type 11 being the most common of the three types. Usher type 11 has been localized to three different chromosomes 1q41, 3p, and 5q, corresponding to Usher type 2A, 213, and 2C respectively. Usherin is a basement membrane protein encoded by the USH2A gene. Expression of usherin has been localized in the basement membrane of several tissues, however it is not ubiquitous. Immunohistochemistry detected usherin in the following human tissues: retina, cochlea, small and large intestine, pancreas, bladder, prostate, esophagus, trachea, thymus, salivary glands, placenta, ovary, fallopian tube, uterus, and testis. Usherin was absent in many other tissues such as heart, lung, liver, kidney, and brain. This distribution is consistent with the usherin distribution seen in the mouse. Conservation of usherin is also seen at the nucleotide and amino acid level when comparing the mouse and human gene sequences. Evolutionary conservation of usherin expression at the molecular level and in tissues unaffected by Usher 2a supports the important structural and functional role this protein plays in the human. In addition, we believe that these results could lead to a diagnostic procedure for the detection of Usher syndrome and those who carry an USH2A mutation. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Boys Town Natl Res Hosp, Omaha, NE 68131 USA. Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE 68182 USA. Massachusetts Eye & Ear Infirm, ENT Dept, Boston, MA 02114 USA. RP Pearsall, N (reprint author), Boys Town Natl Res Hosp, 555 30th St, Omaha, NE 68131 USA. FU NIDCD NIH HHS [P01-DC01813-08] NR 22 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD DEC PY 2002 VL 174 IS 1-2 BP 55 EP 63 AR PII S0378-5955(02)00635-4 DI 10.1016/S0378-5955(02)00635-4 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 618UR UT WOS:000179436100006 PM 12433396 ER PT J AU Rosowski, JJ Lee, CY AF Rosowski, JJ Lee, CY TI The effect of immobilizing the gerbil's pars flaccida on the middle-ear's response to static pressure SO HEARING RESEARCH LA English DT Article DE tympanic membrane; tympanometry; laser Doppler vibrometry ID MONGOLIAN GERBIL; TYMPANIC MEMBRANE; MECHANICS AB The pars flaccida of the tympanic membrane has a small role in regulating middle-ear static pressure (Acta Physiol. Scand. 118 (1983) 337; Hear. Res. 118 (1998) 35) and can also modify the response of the middle ear to low-frequency sound pressures by shunting ear-canal volume velocity around the pars tensa (Hear. Res. 13 (1984) 83; Hear. Res. 106 (1997) 39; Diversity in Auditory Mechanics (1997) 129; Audiol. Neuro-Otol. 4 (1999) 129). It has been hypothesized that these two functions can interact to reduce the effect of middle-ear static pressure on sound transmission through the middle ear (Hear. Res. 153 (2001) 146). This paper tests this hypothesis by measuring the effect of static pressure on the sensitivity of the p. tensa and the coupled malleus to sound, before and after immobilizing the p. flaccida. The results are consistent with a limited role of the p. flaccida in influencing the effect of static pressure on the p. tensa's acoustic response. However, this effect is only observed at low frequencies and over the +/-1 cm H2O range of middle-ear static pressures. The results also suggest that large negative middle-ear pressures can induce a change in the mode of tympanic membrane motion regardless of the state of the p. flaccida. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol & Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA USA. MIT, Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA USA. Natl Taiwan Univ Hosp, Dept Otorhinolaryngol, Taipei, Taiwan. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol & Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 16 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD DEC PY 2002 VL 174 IS 1-2 BP 183 EP 195 AR PII S0378-5955(02)00655-X DI 10.1016/S0378-5955(02)00655-X PG 13 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 618UR UT WOS:000179436100019 PM 12433409 ER PT J AU Chao, TK Burgess, BJ Eddington, DK Nadol, JB AF Chao, TK Burgess, BJ Eddington, DK Nadol, JB TI Morphometric changes in the cochlear nucleus in patients who had undergone cochlear implantation for bilateral profound deafness SO HEARING RESEARCH LA English DT Article DE cochlear nucleus; cochlear implantation; synaptosome-associated protein 25; ventral cochlear nucleus; anterior ventral cochlear nucleus; dorsal cochlear nucleus ID INTRACOCHLEAR ELECTRICAL-STIMULATION; CELL-SIZE CHANGES; HEARING-LOSS; MORPHOLOGY; NERVE; CAT AB We have investigated the morphometric changes in the cochlear nucleus of patients who had undergone cochlear implantation following profound deafness. The brain stems of 11 adult patients who had undergone implantation and four non-implanted control cases with varying degrees of hearing loss were studied. The volumes of the ventral cochlear nucleus (VCN) and dorsal cochlear nucleus (DCN), and the maximal cross-sectional area and densities of cell bodies in the anterior ventral cochlear nucleus (AVCN) were measured bilaterally by light microscopy assisted by the Neurolucida 2000 image analysis system. In addition, the density of synapses on cells of the AVCN were estimated using immunostaining for the synaptosome-associated protein (SNAP-25) by light microscopy. There was no significant difference in volumes of VCN and DCN, maximal cross-sectional area and density of cell bodies of the AVCN, and SNAP-25 immunostaining between the cochlear nucleus ipsilateral and contralateral to cochlear implantation. In addition, there was no significant correlation between these morphometric parameters and clinical performance. Peripheral deafness seems to reduce the size of neurons in the AVCN in that the maximum diameter of cell bodies was greater in the ear with better hearing preoperatively (chi-square test P < 0.05). However, electrical stimulation provided by the cochlear implantation did not alter these morphometric changes in adult cochlear implant patients. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Far Eastern Mem Hosp, Dept Otolaryngol, Taipei, Taiwan. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01DC00152-22] NR 20 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD DEC PY 2002 VL 174 IS 1-2 BP 196 EP 205 AR PII S0378-5955(02)00694-9 DI 10.1016/S0378-5955(02)00694-9 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 618UR UT WOS:000179436100020 PM 12433410 ER PT J AU Foo, NC Ahn, BY Ma, XH Hyun, W Yen, TSB AF Foo, NC Ahn, BY Ma, XH Hyun, W Yen, TSB TI Cellular vacuolization and apoptosis induced by hepatitis B virus large surface protein SO HEPATOLOGY LA English DT Article ID FIBROSING CHOLESTATIC HEPATITIS; LARGE ENVELOPE POLYPEPTIDE; ENDOPLASMIC-RETICULUM; TRANSGENIC MICE; BREFELDIN-A; EXPRESSION; ACTIVATION; INFECTION; SECRETION; ANTIGEN AB Fibrosing cholestatic hepatitis (FCH) is a rapidly progressive form of viral hepatitis B that occurs in severely immunosuppressed patients. Pathologically, the liver in FCH is characterized by widespread hepatocyte vacuolization and apoptosis, which, in contrast to more common forms of hepatitis B, is only rarely associated with significant inflammation. Therefore, it has been proposed that, in FCH, hepatocytes may be injured by a direct cytopathic effect of the virus rather than by the host immune response. In support of this hypothesis, we present evidence that cultured hepatoma cells that had been transfected with a plasmid selectively expressing the viral large surface protein form numerous large vacuoles and undergo apoptosis. The similarity of the cytopathology in FCH in vivo and in these transfected cells in vitro strongly implicates the large surface protein as the direct cause of this acute liver disease. This conclusion is further supported by the published demonstration that hepatocytes tend to accumulate large surface protein in FCH, which may reflect its overexpression by the virus. In conclusion, our data implicate the large surface protein as a major cause of hepatocyte injury in fibrosing cholestatic hepatitis. C1 San Francisco VA Med Ctr, Pathol Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Korea Univ, Dept Life Sci, Seoul 136701, South Korea. RP Yen, TSB (reprint author), Pathol 113B,4150 Clement St, San Francisco, CA 94121 USA. FU NCI NIH HHS [R01CA55578]; NIDDK NIH HHS [P30DK26743] NR 34 TC 49 Z9 66 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2002 VL 36 IS 6 BP 1400 EP 1407 DI 10.1053/jhep.2002.36819 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 620MC UT WOS:000179536300013 PM 12447865 ER PT J AU El-Serag, HB Hampel, H Yeh, C Rabeneck, L AF El-Serag, HB Hampel, H Yeh, C Rabeneck, L TI Extrahepatic manifestations of hepatitis C among United States male veterans SO HEPATOLOGY LA English DT Article ID PORPHYRIA-CUTANEA-TARDA; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; ESSENTIAL MIXED CRYOGLOBULINEMIA; ORAL LICHEN-PLANUS; VIRUS-INFECTION; DIABETES-MELLITUS; LYMPHOPROLIFERATIVE DISEASES; PREVALENCE; ASSOCIATION AB Hepatitis C virus (HCV) has been associated with several extrahepatic conditions. To date, most studies assessing these associations involved small numbers of patients and lacked a control group. Using the computerized databases of the Department of Veterans Affairs, we carried out a hospital-based case-control study that examined all cases of HCV-infected patients hospitalized during 1992 to 1999 (n = 34,204) and randomly chosen control subjects without HCV (n = 136,816) matched with cases on the year of admission. The inpatient and outpatient files were searched for several disorders involving the skin (porphyria cutanea tarda [PCT], vitiligo, and lichen planus); renal (membranous glomerulonephritis [GN] and membranoproliferative glomerulonephritis); hematologic (cryoglobulin, Hodgkin's and non-Hodgkin's lymphoma [NHL]); endocrine (diabetes, thyroiditis); and rheumatologic (Sjogren's syndrome). The association between HCV and these disorders was examined in multivariate analyses that controlled for age, gender, ethnicity, and period of military service. Patients in the case group were younger in age (45 vs. 57 years), were more frequently nonwhite (39.6% vs. 26.3%), and were more frequently male (98.1 % vs. 97.0%). A significantly greater proportion of HCV-infected patients had PCT, vitiligo, lichen planus, and cryoglobulinemia. There was a greater prevalence of membranoproliferative GN among patients with HCV but not membranous GN. There was no significant difference in the prevalence of thyroiditis, Sjogren's syndrome, or Hodgkin's or NHL. However, NHL became significant after age adjustment. Diabetes was more prevalent in controls than cases, but no statistically significant association was found after adjustment for age. In conclusion, we found a significant association between HCV infection and PCT, lichen planus, vitiligo, cryoglobulinemia, membranoproliferative GN, and NHL. Patients presenting with these disorders should be tested for HCV infection. C1 Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Gastroenterol Sect, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [K24 DK259318] NR 50 TC 147 Z9 151 U1 3 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2002 VL 36 IS 6 BP 1439 EP 1445 DI 10.1053/jhep.2002.37191 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 620MC UT WOS:000179536300018 PM 12447870 ER PT J AU Schade, G Hess, M Muller, F Kirchhoff, T Ludwigs, M Hillman, R Kobler, J AF Schade, G Hess, M Muller, F Kirchhoff, T Ludwigs, M Hillman, R Kobler, J TI Physical and technical elements of short-interval, color-filtered double strobe flash-stroboscopy SO HNO LA German DT Article DE short-interval; color-filtered double strobe flash-stroboscopy larynx; laryngoscopy; imaging; vocal folds ID VOCAL FOLD VIBRATIONS; HIGH-SPEED AB Introduction. Quantitative measurement of vocal fold movements can be done either with high-speed imaging or with short-interval, color-filtered double strobe flash-stroboscopy. The physical and technical elements of this new technique are described. Methods. Two special strobe units (KAY Elemetrics RLS 9100) are used in a master-slave configuration. In this way an adjustable interval of 0.1-2.0 ms between flashes is introduced. The strobe flashes are color filtered and are separated by a brief interval. By this means a double exposure is created in each video frame. Real-time visualization of opening and closing velocities over the entire length of the vocal fold from anterior to posterior is possible. Quantification is possible off-line after image calibration. Conclusion. Short-interval,color-filtered double-strobe flash stroboscopy allows quantitative measurement of the velocity of vocal fold movements during vibration at different pitches and sound pressure levels (SPL). Images gained with this new technique provide information about a dynamic property (velocity) of the vocal fold within a single image. Therefore, its use could be helpful from the aspect of clinical documentation. C1 Univ Hamburg, Klinikum Eppendorf, Abt Hor Stimm & Sprachheilkunde, D-20246 Hamburg, Germany. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA USA. RP Schade, G (reprint author), Univ Hamburg, Klinikum Eppendorf, Abt Hor Stimm & Sprachheilkunde, Martinistr 52, D-20246 Hamburg, Germany. OI Muller, Frank/0000-0003-0566-3076 NR 17 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0017-6192 J9 HNO JI HNO PD DEC PY 2002 VL 50 IS 12 BP 1079 EP 1083 DI 10.1007/s00106-002-0709-6 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 626JG UT WOS:000179867600008 PM 12474131 ER PT J AU Lam, P Hui, KM Wang, YM Allen, PD Louis, DN Yuan, CJ Breakefield, XO AF Lam, P Hui, KM Wang, YM Allen, PD Louis, DN Yuan, CJ Breakefield, XO TI Dynamics of transgene expression in human glioblastoma cells mediated by herpes simplex virus/adeno-associated virus amplicon vectors SO HUMAN GENE THERAPY LA English DT Article ID SITE-SPECIFIC INTEGRATION; INVERTED TERMINAL REPEATS; GROWTH-FACTOR RECEPTOR; CONFERS ENHANCED TUMORIGENICITY; BACTERIAL ARTIFICIAL CHROMOSOME; ADENOASSOCIATED VIRUS; REP PROTEINS; DNA-SEQUENCES; PACKAGING SYSTEM; GENE-EXPRESSION AB One of the challenges in gene therapy is to ensure stable transgene expression at the site of disease with a high degree of accuracy and safety. In this paper, we examine both viral and cellular elements that may affect the level of transgene expression mediated by herpes simplex virus type 1 (HSV-1) adeno-associated virus (AAV) amplicon vectors. These elements include the AAV inverted terminal repeats (ITRs), the AAV Rep proteins, and the allelic status of 19q in human glioma cell lines. The latter is of particular interest because the AAV integration site (AAVS1) is located on the long arm of chromosome 19 and 30-40% of human glioblastoma tumors are reported to have loss of heterozygosity in this region of chromosome 19q. Fluorescence-activated cell-sorting analysis results indicate that inclusion of minimal or full-length AAV ITRs in HSV-1 amplicon vectors markedly increases the efficiency of transgene expression. On the other hand, insertion of the AAV rep gene decreases the level of transgene expression, apparently because of the cytotoxic effects of Rep proteins. Further, the levels of transgene expression appear to be independent of 19q allelic status or the number of endogenous AAVS1 sequences in the various glioma cell lines studied. Taken together, these data support employing AAV ITRs, in the context of HSV-1 amplicon vectors, to enhance short-term levels of transgene expression. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02129 USA. Natl Canc Ctr, Div Mol & Cellular Res, Singapore 169610, Singapore. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Dept Neurol, Neurogenet Unit, Bldg 149,13th St,CNY 6205, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu FU NCI NIH HHS [CA69246] NR 70 TC 16 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC PY 2002 VL 13 IS 18 BP 2147 EP 2159 DI 10.1089/104303402320987842 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 766CP UT WOS:000188328100004 PM 12542846 ER PT J AU Ogino, S Wilson, RB AF Ogino, S Wilson, RB TI Genetic testing and risk assessment for spinal muscular atrophy (SMA) SO HUMAN GENETICS LA English DT Review ID MOTOR-NEURON GENE; WERDNIG-HOFFMANN DISEASE; ARTHROGRYPOSIS MULTIPLEX CONGENITA; AMYOTROPHIC-LATERAL-SCLEROSIS; MOLECULAR ANALYSIS; DE-NOVO; RESPIRATORY-DISTRESS; PRENATAL PREDICTION; SMNT GENE; DIAPHRAGMATIC PARALYSIS AB Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases, affecting approximately I in 10,000 live births, and with a carrier frequency of approximately I in 50. Because of gene deletion or conversion, SMN1 exon 7 is homozygously absent in approximately 94% of patients with clinically typical SMA. Approximately 30 small intragenic SMN1 mutations have also been described. These mutations are present in many of the approximately 6% of SMA patients who do not lack both copies of SMN1, whereas SMA of other patients without a homozygous absence of SMN1 is unrelated to SMN1. A commonly used polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) assay can be used to detect a homozygous absence of SMN1 exon 7. SMN gene dosage analyses, which can determine the copy numbers of SMN1 and SMN2 (an SMN1 homolog and a modifier for SMA), have been developed for SMA carrier testing and to confirm that SMN1 is heterozygously absent in symptomatic individuals who do not lack both copies of SMN1. In conjunction with SMN gene dosage analysis, linkage analysis remains an important component of SMA genetic testing in certain circumstances. Genetic risk assessment is an essential and integral component of SMA genetic testing and impacts genetic counseling both before and after genetic testing is performed. Comprehensive SMA genetic testing, comprising PCR-RFLP assay, SMN gene dosage analysis, and linkage analysis, combined with appropriate genetic risk assessment and genetic counseling, offers the most complete evaluation of SMA patients and their families at this time. New technologies, such as haploid analysis techniques, may be widely available in the future. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3rd Floor, Boston, MA 02115 USA. NR 138 TC 85 Z9 97 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 2002 VL 111 IS 6 BP 477 EP 500 DI 10.1007/s00439-002-0828-x PG 24 WC Genetics & Heredity SC Genetics & Heredity GA 623FY UT WOS:000179693700001 PM 12436240 ER PT J AU Adachi, D Oda, T Yagasaki, H Nakasato, K Nakasato, K Taniguchi, T D'Andrea, AD Asano, S Yamashita, T AF Adachi, D Oda, T Yagasaki, H Nakasato, K Nakasato, K Taniguchi, T D'Andrea, AD Asano, S Yamashita, T TI Heterogeneous activation of the Fanconi anemia pathway by patient-derived FANCA mutants SO HUMAN MOLECULAR GENETICS LA English DT Article ID GROUP-A GENE; COMPLEMENTATION GROUP; NUCLEAR ACCUMULATION; PROTEINS FANCA; JAPANESE PATIENTS; FAA; MUTATIONS; COMPLEX; VARIABILITY; LOCALIZATION AB Fanconi anemia (FA) is an autosomal recessive disorder of hematopoiesis characterized by hypersensitivity to DNA crosslinkers such as mitomycin C (MMC). There is growing evidence for a model of the FA pathway, wherein a nuclear multiprotein complex of five FA proteins (FANCA, C, E, F and G) regulates activation of FANCD2 into a monoubiquitinated form, which, collaborating with the BRCA1 machinery, affects cellular response to DNA damage. However, the role of the FA pathway in defective DNA damage response caused by various mutant forms of FA proteins has not been fully assessed. In the present study, 21 patient-derived FANCA mutants with a missense or a small in-frame deletion were expressed in FANCA-deficient fibroblasts and examined for complementation of MMC sensitivity and for reconstitution of the FA pathway: FANCA phosphorylation, interaction with FANCC, FANCF and FANCG and nuclear localization and FANCD2 monoubiquitination. The altered FANCA proteins complemented MMC sensitivity at different grades: five proteins (group I) behaved like wild-type FANCA, whereas the other proteins were either mildly (group II, n=4) or severely (group III, n=12) impaired. Group I proteins showed an apparently normal reconstitution of the FA pathway, thus they may be pathogenic by reducing endogenous expression or possibly benign polymorphisms. Reconstitution of the FA pathway by group II and III mutants closely correlated with cellular sensitivity to MMC. The different activation of the FA pathway may partly account for the phenotypic variation seen in FA patients. C1 Univ Tokyo, Inst Med Sci, Div Gen Diagnosis, Minato Ku, Tokyo 1088639, Japan. Univ Tokyo, Inst Med Sci, Dept Mol Therapy, Adv Clin Res Ctr, Tokyo 1088639, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Yamashita, T (reprint author), Univ Tokyo, Inst Med Sci, Div Gen Diagnosis, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. NR 47 TC 35 Z9 35 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 DEC 1 PY 2002 VL 11 IS 25 BP 3125 EP 3134 DI 10.1093/hmg/11.25.3125 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 622VR UT WOS:000179668300002 PM 12444097 ER PT J AU Wolf, M Sandler, L Jimenez-Kimble, R Shah, A Ecker, JL Thadhani, R AF Wolf, M Sandler, L Jimenez-Kimble, R Shah, A Ecker, JL Thadhani, R TI Insulin resistance but not inflammation is associated with gestational hypertension SO HYPERTENSION LA English DT Article DE hypertension, gestational; insulin resistance; prospective studies ID HORMONE-BINDING GLOBULIN; GLUCOSE-TOLERANCE; PREGNANT-WOMEN; PREECLAMPSIA; RISK; DISEASE; HYPERINSULINEMIA; ATHEROSCLEROSIS; DISORDERS; PRESSURE AB Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of pregnancy-associated morbidity. Although insulin resistance and inflammation contribute to preeclampsia, prospective data regarding mechanisms of gestational hypertension are sparse. We conducted a prospective, nested case-control study to test the hypotheses that insulin resistance, marked by reduced sex hormone-binding globulin (SHBG) levels, and inflammation, marked by increased C-reactive protein levels, are similarly associated with gestational hypertension. We measured first-trimester C-reactive protein and SHBG levels in 51 women who subsequently developed gestational hypertension and 102 randomly selected normotensive pregnant controls. Compared with controls, first-trimester SHBG levels were significantly reduced among women who later developed gestational hypertension (176+/-73 versus 203+/-79 nmol/L; P = 0.03), but there was no difference in C-reactive protein levels. There was statistically significant interaction among nulliparity, first-trimester SHBG levels, and risk of gestational hypertension, such that increasing SHBG levels were associated with significantly reduced risk of gestational hypertension among nulliparous women (odds ratio, 0.64 per 50-nmol/L increase; 95% confidence interval, 0.46, 0.90; P<0.01) but not among multiparous women. This association remained significant after adjusting for potential confounders (odds ratio, 0.55; 95% confidence interval, 0.31, 0.98; P=0.04). We conclude that insulin resistance, but not inflammation, is an independent risk factor for gestational hypertension among nulliparous women. Furthermore, important mechanistic differences exist in the pathogenesis of gestational hypertension comparing nulliparous and multiparous women. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Wolf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NHLBI NIH HHS [HL03804, HL04095]; NICHD NIH HHS [HD39223] NR 42 TC 40 Z9 41 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2002 VL 40 IS 6 BP 886 EP 891 DI 10.1161/01.HYP.0000042085.65467.9F PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 625XR UT WOS:000179841300019 PM 12468574 ER PT J AU Acar, B Beaulieu, CF Gokturk, SB Tomasi, C Paik, DS Jeffrey, RB Yee, J Napel, S AF Acar, B Beaulieu, CF Gokturk, SB Tomasi, C Paik, DS Jeffrey, RB Yee, J Napel, S TI Edge displacement field-based classification for improved detection of polyps in CT colonography SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE computed tomographic colonography (CTC); computer-aided diagnosis; edge displacement fields (EDFs); fiber-optic colonoscopy (FOC) ID COLORECTAL POLYPS; VIRTUAL COLONOSCOPY; SPIRAL CT; COLON; COLOGRAPHY; VISUALIZATION; FEASIBILITY; IMAGES; ENDOSCOPY; DISPLAY AB Colorectal cancer can easily be prevented provided that the precursors to tumors, small colonic polyps, are detected and removed. Currently, the only definitive examination of the colon is fiber-optic colonoscopy, which is invasive and expensive. Computed tomographic colonography (CTC) is potentially a less costly and less invasive alternative to FOC. It would be desirable to have computer-aided detection (CAD) algorithms to examine the large amount of data CTC provides. Most current CAD algorithms have high false positive rates at the required sensitivity levels. We developed and evaluated a postprocessing algorithm to decrease the false positive rate of such a CAD method without sacrificing sensitivity. Our method attempts to model the way a radiologist recognizes a polyp while scrolling a cross-sectional plane through three-dimensional computed tomography data by classification of the changes in the location of the edges in the two-dimensional plane. We performed a tenfold cross-validation study to assess its performance using sensitivity/specificity analysis on data from 48 patients. The mean specificity over all experiments increased from 0.19 (0.35) to 0.47 (0.56) for a sensitivity of 1.00 (0.95). C1 Stanford Univ, LUCAS MRS Ctr, Dept Radiol, Lab 3D, Stanford, CA 94305 USA. Stanford Univ, Dept Elect Engn & Comp Sci, Stanford, CA 94305 USA. Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. RP Acar, B (reprint author), Stanford Univ, LUCAS MRS Ctr, Dept Radiol, Lab 3D, Stanford, CA 94305 USA. RI Acar, Burak/C-7904-2009 OI Acar, Burak/0000-0003-4818-9378 FU NCI NIH HHS [1R01 CA72023] NR 35 TC 62 Z9 65 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 2002 VL 21 IS 12 BP 1461 EP 1467 DI 10.1109/TMI.2002.806405 PG 7 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 643QC UT WOS:000180871100003 PM 12588030 ER PT J AU Cameron, TO Cohen, GB Islam, SA Stern, LJ AF Cameron, TO Cohen, GB Islam, SA Stern, LJ TI Examination of the highly diverse CD4(+) T-cell repertoire directed against an influenza peptide: a step towards TCR proteomics SO IMMUNOGENETICS LA English DT Article DE T lymphocytes; antigens/peptides/epitopes; T-cell receptors; T-cell receptor repertoire; proteomics ID ANTIGEN-SPECIFIC CD4(+); LEUKEMIA-VIRUS TYPE-1; CRYSTAL-STRUCTURE; FINE SPECIFICITY; RECEPTOR; HEMAGGLUTININ; LYMPHOCYTES; COMPLEX; RECOGNITION; REGIONS AB We combined several recent technological advances in immunology and molecular biology to identify and sequence a large number of T-cell receptor (TCR) genes specific for a particular antigen. We utilized class II MHC tetramers and interferon-gamma surface capture to isolate from samples of peripheral blood the population of CD4(+) T cells responding to a peptide derived from influenza hemagglutinin and restricted by HLA-DR1. Detailed analysis of hundreds of clones from three different patients revealed an extremely diverse repertoire, with little overlap between patients. We observed no dominant usage of particular Vbeta segments nor any clear CDR3 sequence motif in the responding T cells, but most of the clones appear to utilize acidic residues in the CDR1 and CDR3 regions, presumably to interact with the exposed basic residues in the MHC-peptide complex. This methodology could be expanded to a large scale to identify the generalized rules governing TCR-MHC engagement and factors which shape the T-cell repertoire after vaccination and in autoimmune pathologies. C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Immunol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Stern, LJ (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA. FU NIAID NIH HHS [N01-AI-95361]; NIGMS NIH HHS [T32-GM08334] NR 43 TC 17 Z9 17 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD DEC PY 2002 VL 54 IS 9 BP 611 EP 620 DI 10.1007/s00251-002-0508-y PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 629DM UT WOS:000180035200001 PM 12466894 ER PT J AU West, CA He, C Young, AJ So, M Zhao, T Swanson, SJ Mentzer, SJ AF West, CA He, C Young, AJ So, M Zhao, T Swanson, SJ Mentzer, SJ TI Spatial variation of plasma flow in the oxazolone-stimulated microcirculation SO INFLAMMATION RESEARCH LA English DT Article DE microcirculation; blood flow; fluorescent dye; dextran; sheep ID BLOOD-FLOW; EFFERENT LYMPH; CELL-MIGRATION; MICROVASCULATURE; ULTRASTRUCTURE; MICROVESSELS; ORGANIZATION; MORPHOLOGY; MESENTERY; SKIN AB Introduction: In cutaneous lymphocytic inflammation, enhanced regional blood flow is suggested by persistent erythema and warmth. Direct assessment of the microcirculation, however, has been limited by tissue edema and skin thickness. Methods: To assess the microcirculatory adaptations to the epicutaneous antigen oxazolone, we studied the first pass kinetics and microvascular topography of the inflammatory skin microcirculation using a specially adapted epi-illumination intravital microscopy system. The fluorescence intravital videomicroscopy and streaming image acquisition of fluorescein-labeled dextran (similar to500,000 MW) injections were used to assess changes in plasma flow. Results: Direct plasma tracer injections of both the oxazolone-stimulated and control microcirculation demonstrated comparable transit times (leading edge and intensity-weighted peak times) from the carotid artery to the superficial vascular plexus (p > 0.05). In contrast to transit times, continuous infusion of the plasma tracer demonstrated a significant increase in the delivery of the fluorescein-labeled dextran to the oxazolone-stimulated microcirculation. Quantitative morphometry of intravital microscopic images demonstrated a 2.2-fold increase in the mean diameter of vessels in the superficial vascular plexus (p < 0.01). Further, fluorescence intensity mapping indicated that the increase was associated with increased perfusion of focal regions of the superficial vascular plexus (p < 0.001). Conclusions: These results indicate that the oxazolone-stimulated adaptations of the inflammatory microcirculation include both microvascular dilatation and the redistribution of plasma flow. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunophysiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Surg Res Labs, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunophysiol Lab, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL47078] NR 35 TC 3 Z9 3 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD DEC PY 2002 VL 51 IS 12 BP 572 EP 578 AR PII 1023-3830/02/120572-07 DI 10.1007/PL00012431 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 641XX UT WOS:000180773300002 PM 12558190 ER PT J AU Sutton, JP Jamieson, IMD AF Sutton, JP Jamieson, IMD TI Reconfigurable networking for coordinated multi-agent sensing and communications SO INFORMATION SCIENCES LA English DT Article AB An implementation of a neurally-inspired system comprised of multiple mobile sensor-effector agents is described. Each agent ha's features of a complex neural network that is able to communicate and adjust its behavior depending upon a variety of parameters, including changes in the environment and the behavior of other agents. The system as a whole spatiotemporally reconfigures itself to perform coordinated behaviors not obtainable with single agents. Transient clustering of agents into functional subsystems to perform specific tasks generates a "system of systems" architecture. The interesting findings of this dynamic platform show that (a) the formation and dissolution of functional subsystems is a local phenomenon without the need for global control and (b) minimal intermittent communication among the agents can yield large-scale, coordinated, goal-driven behavior under a wide range of conditions. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, MIT, Massachusetts Gen Hosp, Neural Syst Grp,Div Hlth Sci & Technol, Charlestown, MA 02129 USA. RP Sutton, JP (reprint author), Harvard Univ, MIT, Massachusetts Gen Hosp, Neural Syst Grp,Div Hlth Sci & Technol, Bldg 149,9th Floor,13th St, Charlestown, MA 02129 USA. NR 2 TC 3 Z9 3 U1 4 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0020-0255 J9 INFORM SCIENCES JI Inf. Sci. PD DEC PY 2002 VL 148 IS 1-4 BP 103 EP 111 AR PII S0020-0255(02)00282-7 DI 10.1016/S0020-0255(02)00282-7 PG 9 WC Computer Science, Information Systems SC Computer Science GA 623HJ UT WOS:000179697000009 PM 14983838 ER PT J AU Ponugoti, B Papasani, MR Layman, JA Gensure, R Juppner, H Rubin, DA AF Ponugoti, B Papasani, MR Layman, JA Gensure, R Juppner, H Rubin, DA TI Molecular isolation and evolution of teleost parathyroid hormones (PTH), PTH-related peptides (PTHrP) and tuberoinfundibular peptides of 39 residues (TIP39). SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 02-07, 2002 CL ANAHEIM, CALIFORNIA SP Soc Integrat & Comparat Biol C1 Illinois State Univ, Normal, IL 61761 USA. Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RI PONUGOTI, BHASKAR/H-2230-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC INTEGRATIVE COMPARATIVE BIOLOGY PI MCLEAN PA 1313 DOLLEY MADISON BLVD, NO 402, MCLEAN, VA 22101 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD DEC PY 2002 VL 42 IS 6 BP 1296 EP 1296 PG 1 WC Zoology SC Zoology GA 669ND UT WOS:000182356600573 ER PT J AU Pino, RM AF Pino, RM TI Neuromuscular blocker studies of critically ill patients SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID CARE UNIT PATIENTS; PROLONGED PARALYSIS; NATIONAL SURVEY; AGENTS; VECURONIUM; FAILURE C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Pino, RM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, 55 Fruit St, Boston, MA 02114 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2002 VL 28 IS 12 BP 1695 EP 1697 DI 10.1007/s00134-002-1510-4 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 641PH UT WOS:000180753600002 PM 12580152 ER PT J AU Burger, AJ D'Elia, JA Weinrauch, LA Lerman, I Gaur, A AF Burger, AJ D'Elia, JA Weinrauch, LA Lerman, I Gaur, A TI Marked abnormalities in heart rate variability are associated with progressive deterioration of renal function in type I diabetic patients with overt nephropathy SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE heart rate variability; diabetes mellitus; nephropathy; autonomic neuropathy ID CARDIAC AUTONOMIC NEUROPATHY; URINARY ALBUMIN EXCRETION; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; SPECTRAL-ANALYSIS; FOLLOW-UP; DYSFUNCTION; HYPERTENSION; MICROALBUMINURIA; PREVALENCE AB Background: Cardiac autonomic neuropathy is a common complication of long-standing, type I diabetes and is associated with increased morbidity and mortality. Impaired heart rate variability is a sensitive and reproducible marker of cardiac autonomic neuropathy. We sought to examine the relationship between cardiac autonomic neuropathy as assessed by heart rate variability and overt nephropathy, with emphasis on the progression of renal dysfunction over I year. Method: Baseline and 12 month clinical and biochemical characteristics, as well as autonomic function tests, were analyzed in 23, type I diabetic patients (mean age 37-10 years, 65% males), who were prospectively enrolled as a part of a multi-center investigation. In addition, ambulatory, 24-h, 3-channel electrocardiograms were recorded, and heart rate variability indices were assessed in the time and frequency domains over the same period. Results: All heart rate variability indices were markedly decreased in our study population. On univariate analysis, heart rate variability was associated with creatinine clearance, and to a lesser extent, mean 24-h blood pressures and cholesterol. On multivariate analysis, only heart rate variability was a significant and independent predictor of abnormalities in creatinine clearance. Severe reduction in heart rate variability at baseline was also significantly associated with the further deterioration in renal function at I year. Conclusion: Heart rate variability is significantly reduced in long-standing, type 1 diabetics with proteinuria or overt nephropathy. Marked abnormalities in heart rate variability are significantly associated with and predictive of progressive renal deterioration at 1 year. These findings may have implications for aggressive medical intervention to improve prognosis and survival in this population. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Noninvas Cardiol Lab, Boston, MA 02215 USA. Inst Nacl Nutr Salvador Zubiran, Dept Endocrinol, Mexico City 14000, DF, Mexico. Mt Auburn Hosp, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Burger, AJ (reprint author), Beth Israel Deaconess Med Ctr, 1 Deaconess Rd,Baker 3, Boston, MA 02215 USA. OI Weinrauch, Larry/0000-0003-1357-9528 NR 34 TC 22 Z9 25 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD DEC PY 2002 VL 86 IS 2-3 BP 281 EP 287 AR PII S0167-5273(02)00346-7 DI 10.1016/S0167-5273(02)00346-7 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 617NE UT WOS:000179367100020 PM 12419567 ER PT J AU Steiner-Adair, C Sjostrorn, L Franko, DL Pai, S Tucker, R Becker, AE Herzog, DB AF Steiner-Adair, C Sjostrorn, L Franko, DL Pai, S Tucker, R Becker, AE Herzog, DB TI Primary prevention of risk factors for eating disorders in adolescent girls: Learning from practice SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE eating disorders; prevention; adolescence; risk; risk factors and curriculum ID BODY-IMAGE; ATTITUDES; PROGRAM; POPULATION; QUESTIONNAIRE; INTERVENTION; ESTEEM AB Objective: This study evaluates the effectiveness and feasibility of a primary prevention program for risk factors for eating disorders in adolescent girls. Method: Nearly 500 seventh-grade girls participated in "Full of Ourselves: Advancing Girl Power, Health, and Leadership," and were assessed at baseline, immediately after program completion, and 6 months later on several self-report measures of knowledge, body image, and eating and weight-related behaviors. Results: Significant differences were found between participants and controls on measures of knowledge and weight-related body esteem, which were maintained at 6-month follow-up. Eating related behaviors, including skipping meals and dieting, appeared unaffected by program participation. Discussion: The program was feasible, safe, and resulted in positive and maintained changes in knowledge and weight satisfaction for adolescent girls. (C) 2002 by Wiley Periodicals, Inc. C1 Harvard Eating Disorders Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Franko, DL (reprint author), Massachusetts Gen Hosp, Harvard Eating Disorders Ctr, WACC 725,15 Parkman St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK49587] NR 36 TC 36 Z9 37 U1 5 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD DEC PY 2002 VL 32 IS 4 BP 401 EP 411 DI 10.1002/eat.10089 PG 11 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 611GV UT WOS:000179008800003 PM 12386905 ER PT J AU Weintraub, JM Willett, WC Rosner, B Colditz, GA Seddon, JM Hankinson, SE AF Weintraub, JM Willett, WC Rosner, B Colditz, GA Seddon, JM Hankinson, SE TI A prospective study of the relationship between body mass index and cataract extraction among US women and men SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE cataract; obesity; diabetes ID POSTERIOR CAPSULE OPACIFICATION; C-REACTIVE PROTEIN; LENS EPITHELIAL-CELLS; AGE-RELATED CATARACT; RISK-FACTORS; CALORIC RESTRICTION; SUBCAPSULAR CATARACTS; LOGISTIC-REGRESSION; CIGARETTE-SMOKING; DIABETES-MELLITUS AB BACKGROUND: Obesity may influence several physiologic processes involved in cataract formation such as oxidative stress, glycosylation and osmotic stress. OBJECTIVE: To examine the association between increased body mass index (BMI) and the incidence of cataract extraction. DESIGN AND SETTING: The Nurses' Health Study and the Health Professionals Follow-up Study, both prospective cohort studies of US women and men. SUBJECTS: A total of 87 682 women and 45 549 men aged 45y and older who did not have diagnosed cataract or cancer at baseline (11980 for women, 1986 for men). MEASUREMENTS: Cataract extractions occurring between baseline and 1996, confirmed by medical records. RESULTS: During 16y of follow-up in the women, and 10y in the men, (1 097997 person-y), 4430 incident cases were documented. Compared to participants with BMI less than 23 kg/m(2), those with BMI greater than or equal to 30 kg/m(2) had 36% higher risk of any type of cataract (pooled multivariate relative risk (RR), 1.36; 95% Cl, 1.23-1.49) after adjusting for smoking, age and lutein/zeaxanthin intake. The association was strongest for posterior subcapsular (PSC) cataract (pooled multivariate RR, 1.99; 95% Cl, 1.55 - 2.55). With adjustment for diabetes, the RR of obesity associated with posterior subcapsular cataract was 1.68 (95% Cl, 1.30-2.17). Obesity was not significantly associated with nuclear cataract. CONCLUSION: Obesity increases the risk of developing cataract overall, and of PSC cataract in particular; the etiology of PSC cataract may be mediated at least in part by glucose intolerance and insulin resistance, even in the absence of clinical diabetes. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Weintraub, JM (reprint author), City & Cty San Francisco Dept Publ Hlth, Environm Hlth Sect, 1390 Market St,Suite 910, San Francisco, CA 94102 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356]; NEI NIH HHS [EY12269, EY09611]; NIDDK NIH HHS [DK46200]; NIEHS NIH HHS [T32 ES07069] NR 46 TC 40 Z9 43 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2002 VL 26 IS 12 BP 1588 EP 1595 DI 10.1038/sj.ijo.802158 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 626HV UT WOS:000179866500008 PM 12461675 ER PT J AU Vazquez, M Greulich-Bode, KM Arsuaga, J Cornforth, MN Bruckner, M Sachs, RK Hlatky, L Molls, M Hahnefeldt, P AF Vazquez, M Greulich-Bode, KM Arsuaga, J Cornforth, MN Bruckner, M Sachs, RK Hlatky, L Molls, M Hahnefeldt, P TI Computer analysis of mFISH chromosome aberration data uncovers an excess of very complicated metaphases SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; INDUCED GENOMIC INSTABILITY; DOUBLE-STRAND BREAKS; INDUCED CELL DEATH; HUMAN-LYMPHOCYTES; IONIZING-RADIATION; X-RAYS; REPRODUCTIVE DEATH; MAMMALIAN-CELLS; MOUSE EMBRYOS AB Purpose: To analyse spectra of chromosome aberrations induced in vitro by low LET radiation, in order to characterize radiation damage mechanisms quantitatively. Methods: Multiplex fluorescence in vitro hybridization (mFISH) allows the simultaneous identification of each homologous chromosome pair by its own colour, mFISH data, specifying number distributions for colour junctions in metaphase of human peripheral blood lymphocytes 72 hours after exposure in vitro to a 3 Gy gamma-ray dose, were combined with similar, previously published results. Monte Carlo computer implementations of radiobiological models for chromosome aberration production guided quantitative analyses, which took into account distribution of cells among different metaphases and lethal effects or preferential elimination of some aberrations at cell division. Results and Conclusions: Standard models of DNA damage induction/repair/misrepair explain the main trends of the data as regards the fraction of metaphases having a particular number of colours involved in colour junctions. However, all standard models systematically under-predict the observed fraction of metaphases where a large number of different chromosomes participate in aberrations. An early appearance of chromosomal instability could explain most of the discrepances. C1 Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Tech Univ Munich, Dept Radiat Oncol, D-8000 Munich, Germany. German Canc Res Ctr, Dept Skin Carcinogenesis, D-6900 Heidelberg, Germany. Harvard Univ, Sch Med, DFCI, Boston, MA 02115 USA. Univ Texas, Med Branch, Dept Radiat Oncol, Galveston, TX 77555 USA. RP Vazquez, M (reprint author), Univ Calif Berkeley, Dept Math, MC3840, Berkeley, CA 94720 USA. FU NCI NIH HHS [CA86823]; NIGMS NIH HHS [GM 57245]; PHS HHS [76260] NR 73 TC 14 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD DEC PY 2002 VL 78 IS 12 BP 1103 EP 1115 DI 10.1080/09553000210166354 PG 13 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 626FN UT WOS:000179861700005 PM 12556338 ER PT J AU Shipley, WU Lu, JD Pilepich, MV Heydon, K Roach, M Wolkov, HB Sause, WT Rubin, P Lawton, CA Machtay, M AF Shipley, WU Lu, JD Pilepich, MV Heydon, K Roach, M Wolkov, HB Sause, WT Rubin, P Lawton, CA Machtay, M TI Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: A secondary analysis of the randomized protocol RTOG 86-10 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; external beam radiotherapy; neoadjuvant hormonal therapy; salvage hormonal therapy ID RADIATION-THERAPY; ONCOLOGY GROUP; DEFINITIVE RADIOTHERAPY; CARCINOMA; DEPRIVATION; GOSERELIN; SURVIVAL; TRIALS AB Purpose: To compare, by a secondary analysis, the therapeutic benefits of androgen suppression in protocol prostate cancer patients with relapse after radiotherapy (RT) for locally advanced disease who, in the Phase III trial beginning in 1987, were assigned to receive or not receive a short course of neoadjuvant maximal androgen suppression before definitive RT. Methods and Materials: Between 1987 and 1991, 456 patients were entered in the Radiation Therapy Oncology Group trail 86-10 and randomized to receive (Arm 1) or not to receive (Ann 11) neoadjuvant hormonal therapy (HT), which was 4 months of goserelin (3.6 mg every 4 weeks) and flutamide (250 mg t.i.d.) before and during RT for bulky T2-T4 tumors. The overall and disease-specific survival after both randomization and salvage HT for patients with relapse was evaluated, as well as the duration of response in those patients undergoing salvage HT. The outcomes in patients who had received neoadjuvant HT vs. those who had not were compared. The median follow-up after randomization for all alive patients was 9.0 years and was 5.5 years for alive patients after beginning salvage HT. Results: Fewer patients received salvage HT on Arm I than on Arm 11 (45% vs. 63%, p < 0.001). The outcomes by randomized treatment arm (I vs. 11) from the time of beginning salvage HT were similar. At 5 years after salvage HT, the overall survival rates were 41% and 41% and the disease-specific survival rates were 50% and 50%. At 8 years after randomization, the overall survival rates were 47% and 44% and the disease-specific survival rates were 55% and 56%. Conclusion: Although a 4-month course of neoadjuvant and concurrent maximum androgen suppression and RT (compared with RT alone) significantly increases the freedom from relapse rate and freedom from receiving salvage HT, it does not compromise the long-term beneficial effect of subsequent salvage HT, if needed for relapse. These findings with long follow-up in patients treated for locally advanced disease diagnosed 9-14 years previously should help allay concerns of the possible development of "resistance" to androgen suppression when 4-month courses of neoadjuvant HT are used before primary treatment. (C) 2002 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Radiat Oncol Ctr, Sacramento, CA USA. LDS Hosp, Salt Lake City, UT USA. Univ Rochester, Rochester, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Shipley, WU (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA-32115, CA-21661] NR 16 TC 41 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2002 VL 54 IS 5 BP 1302 EP 1310 AR PII S0360-3016(02)03052-3 DI 10.1016/S0360-3016(02)03052-3 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 621AJ UT WOS:000179566100003 PM 12459350 ER PT J AU D'Amico, AV Toupless, G Lopes, L Valentine, KJ Cormack, RA Tempany, CM Kumar, S Marks, PJ AF D'Amico, AV Toupless, G Lopes, L Valentine, KJ Cormack, RA Tempany, CM Kumar, S Marks, PJ TI Self-administration of untested medical therapy for treatment of prostate cancer can lead to clinically significant adverse events SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID SELECT C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. OI Cormack, Robert/0000-0001-5553-9984 NR 7 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2002 VL 54 IS 5 BP 1311 EP 1313 AR PII S0360-3016(02)03755-0 DI 10.1016/S0360-3016(02)03755-0 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 621AJ UT WOS:000179566100004 PM 12459351 ER PT J AU Dumont, RA Zhao, YD Holt, JR Bahler, M Gillespie, PG AF Dumont, RA Zhao, YD Holt, JR Bahler, M Gillespie, PG TI Myosin-I isozymes in neonatal rodent auditory and vestibular epithelia SO JARO LA English DT Article DE myosin; hair cells; stereocilia; adaptation; transduction ID SENSORY HAIR-CELLS; MECHANOELECTRICAL TRANSDUCTION; UNCONVENTIONAL MYOSIN; BULLFROGS SACCULUS; BLOCK ADAPTATION; ATPASE ACTIVITY; MOUSE UTRICLE; LOCALIZATION; EAR; RAT AB Myosin isozymes are essential for hair cells, the sensory cells of the inner ear. Because a myosin-I subfamily member may mediate adaptation of mechanoelectrical transduction, we examined expression of all eight myosin-I isozymes in rodent auditory and vestibular epithelia. Using RT-PCR, we found prominent expression of three isozymes, Myo1b (also known as myosin-Ialpha or myr 1), Myolc (myosin-Ibeta or myr 2), and Myo1e (myr 3). By contrast, Myo1a (brush-border myosin-I), Myo1d (myosin 1gamma or myr 4), Myo1f, Myo1g, and Myo1h were less readily amplified. Because sequence analysis demonstrated that the RTPCR products encoded the appropriate isozymes, this represents the first demonstration of expression of all eight mouse myosin-I genes. Using immunocytochemistry with isozyme-selective antibodies, we found that Myo1b was located at apical surfaces of supporting cells that surround hair cells in auditory epithelia of postnatal rats. In vestibular epithelia, Myo1b was present in a ring within the apical pole of the hair cell. In both cases, expression was prominent only immediately after birth. Myo1e was found in hair cells of the auditory and vestibular epithelia; this isozyme was enriched in the cuticular plate, the actin meshwork that anchors the stereocilia. Myolc was found in hair-cell stereocilia, concentrated towards their tips; we confirmed this localization by using adenovirus vectors to direct expression of a GFP-Myo1c tail fusion protein; this fusion protein localized to plasma membranes, often concentrating at stereociliary tips. Myolc therefore remains the myosin isozyme best localized to carry out transducer adaptation. C1 Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA. Johns Hopkins Univ, Dept Physiol, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Munster, Inst Allgemeine Zool & Genet, D-4400 Munster, Germany. Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gillespie, PG (reprint author), Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, L335A,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Barr-Gillespie, Peter/0000-0002-9787-5860 FU NIDCD NIH HHS [DC00304, DC02368, DC03279] NR 60 TC 44 Z9 50 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD DEC PY 2002 VL 3 IS 4 BP 375 EP 389 DI 10.1007/s101620020049 PG 15 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 628RL UT WOS:000180010300001 PM 12486594 ER PT J AU Klerman, EB Shanahan, TL Brotman, DJ Rimmer, DW Emens, JS Rizzo, JF Czeisler, CA AF Klerman, EB Shanahan, TL Brotman, DJ Rimmer, DW Emens, JS Rizzo, JF Czeisler, CA TI Photic resetting of the human circadian pacemaker in the absence of conscious vision SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE photic; circadian; blind; melatonin; phase shift; human ID SUPRACHIASMATIC NUCLEUS; MELATONIN REGULATION; ACTION SPECTRUM; BLIND SUBJECTS; GLUTAMATE MSG; NON-CONE; NON-ROD; RHYTHMS; MICE; ENTRAINMENT AB Ocular light exposure patterns are the primary stimuli for entraining the human circadian system to the local 24-h day. Many totally blind persons cannot use these stimuli and, therefore, have circadian rhythms that are not entrained. However, a few other-wise totally blind persons retain the ability to suppress plasma melatonin concentrations after ocular light exposure, Probably using a neural pathway that includes the site of the human circadian pacemaker, suggesting that light information is reaching this site. To test definitively whether ocular light exposure could affect the circadian pacemaker of some blind persons and whether melatonin suppression in response to bright light correlates with light-induced phase shifts of the circadian system, the authors performed experiments with 5 totally blind volunteers using a protocol known to induce phase shifts of the circadian pacemaker in sighted individuals. In the 2 blind individuals who maintained light-induced melatonin suppression, the circadian system was shifted by appropriately timed bright-light stimuli. These data demonstrate that light can affect the circadian pacemaker of some totally blind individuals-either by altering the phase of the circadian pacemaker or by affecting its amplitude. They are consistent with data from animal studies demonstrating that there are different neural pathways and retinal cells that relay photic information to the brain: one for conscious light perception and the other for non-image-forming functions. C1 Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, Boston, MA 02114 USA. RP Klerman, EB (reprint author), Brigham & Womens Hosp, Dept Med, Div Sleep Med, 221 Longwood Ave, Boston, MA 02115 USA. RI Jelinek, Milan/C-8515-2011 FU NCRR NIH HHS [NCRR-GCRC-M01-RR02635]; NIA NIH HHS [5-K01-AG00661-02, K01 AG000661, K01 AG000661-05, NIA-1-P01-AG09975, NIA-1-R01-AG06072]; NIMH NIH HHS [NIMH-1-R01-MH45130] NR 52 TC 67 Z9 74 U1 3 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD DEC PY 2002 VL 17 IS 6 BP 548 EP 555 DI 10.1177/0748730402238237 PG 8 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 616GM UT WOS:000179296100007 PM 12465888 ER PT J AU Fairfield, KM Emmons, KM Rigotti, NA Colditz, GA AF Fairfield, KM Emmons, KM Rigotti, NA Colditz, GA TI Use of a computerized risk-appraisal instrument for cancer prevention education of medical students SO JOURNAL OF CANCER EDUCATION LA English DT Article ID HEALTH PROMOTION; PRIMARY-CARE; RECOMMENDATIONS; PRACTITIONERS; VIDEODISC; INDEX AB Background. Interactive computer-based tools are increasingly used for patient and medical student instruction. Method. To assess medical students' responses to a computer-based risk-appraisal instrument aimed at teaching concepts of risk and cancer prevention, and to evaluate perceived barriers to using such tools in clinical practice and knowledge about risk factors for colon cancer. Design. An electronic survey of 133 second-year medical students elicited their responses to the instrument after using it for a case-based learning exercise. Results. The students identified several potential barriers to use, including inadequate time during the office visit (75% of students) and problems with literacy (48%). They were generally knowledgeable about risk factors for colon cancer. 84% found the instrument "very helpful" or "somewhat helpful" in understanding a case patient's health and setting priorities for behavioral changes. Conclusions. Medical students may benefit from exposure to interactive, computer-based tools such as health-appraisal instruments when learning skills in risk counseling and cancer prevention. Second-year students were already concerned about having adequate time during office visits to use such instruments. C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Fairfield, KM (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Ly-330,330 Brookline Ave, Boston, MA 02215 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA57711-08] NR 15 TC 4 Z9 4 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD WIN PY 2002 VL 17 IS 4 BP 183 EP 185 PG 3 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 633VK UT WOS:000180305000002 PM 12556051 ER PT J AU Park, EB Emmons, KM Malloy, NW Seifer, E AF Park, EB Emmons, KM Malloy, NW Seifer, E TI A qualitative exploration of health perceptions and behaviors among adult survivors of childhood cancers SO JOURNAL OF CANCER EDUCATION LA English DT Article ID LONG-TERM SURVIVORS; PEDIATRIC CANCER; SMOKING AB Background. Adult survivors of childhood cancer are a growing population. The objective of this study was to draw upon qualitative methods to learn more about survivors' perceived health risks and health behaviors. Methods. Three focus groups and nine individual interviews were conducted. Results. Participants' responses varied in meaning of survivor status, relatedness to other survivors, and health risk comparisons to non-survivors. Survivors expressed uncertainty about control over their health. Conclusions. The identity, health perceptions, and behaviors of adult survivors of childhood cancer are complex. Health promotion programs for survivors should be tailored to individual health risk status and should include a physician-delivered component. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Park, EB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,904A, Boston, MA 02114 USA. FU NCI NIH HHS [5 R01 CA77780] NR 24 TC 4 Z9 4 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD WIN PY 2002 VL 17 IS 4 BP 211 EP 215 PG 5 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 633VK UT WOS:000180305000009 PM 12556058 ER PT J AU Carabello, BA AF Carabello, BA TI Concentric versus eccentric remodeling SO JOURNAL OF CARDIAC FAILURE LA English DT Article; Proceedings Paper CT 17th World Congress of the International-Society-for-Heart-Research CY JUL 12-14, 2001 CL MINNEAPOLIS, MINNESOTA SP Int Soc Heart Res DE hypertrophy; valvular heart disease; and ventricular function ID CHRONIC MITRAL REGURGITATION; HUMAN LEFT-VENTRICLE; AORTIC-STENOSIS; EJECTION PERFORMANCE; WALL STRESS; DETERMINANTS; HYPERTROPHY; AFTERLOAD; PRESSURE; OVERLOAD AB Cardiac hypertrophy has long been recognized as one of the heart's mechanisms for compensating a pressure or volume overload. This compensation has often been viewed as a feedback loop in which the concentric hypertrophy, which develops in pressure overload, normalizes wall stress while the eccentric hypertrophy, which develops in volume overload, allows for an increase in total stroke volume to compensate that which is lost from regulation. While the concentric hypertrophy of pressure overload often is compensatory, many examples are noted where either too little hypertrophy occurs to normalize stress or in other cases, in which hypertrophy exceeds the amount needed for normalization. These observations invoke nonmechanical mechanisms which modulate the degree to which the mechanical signal of pressure overload is translated into an increase in myocardial mass. Hypertrophy develops when the rate of myocardial protein synthesis exceeds that of protein degradation. It now appears that in pressure overload this imbalance is created as synthesis rate increases while in volume overload hypertrophy appears to accrue because degradation rate decreases. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. RP Carabello, BA (reprint author), 2002 Holcombe Blvd,111MCL, Houston, TX 77030 USA. NR 18 TC 49 Z9 52 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2002 VL 8 IS 6 SU S BP S258 EP S263 DI 10.1054/jcaf.2002.129250 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DF UT WOS:000180263400004 PM 12555129 ER PT J AU Dorn, GW Mann, DL AF Dorn, GW Mann, DL TI Signaling pathways involved in left ventricular remodeling: Summation SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material C1 Houston Vet Adm Med Ctr, Winters Ctr Heart Failure Res, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Cincinnati, Dept Med, Cardiol Sect, Cincinnati, OH 45221 USA. RP Mann, DL (reprint author), VA Med Ctr, Cardiol Res, 151C,2002 Holcombe Blvd, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 NR 0 TC 0 Z9 0 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2002 VL 8 IS 6 SU S BP S387 EP S388 DI 10.1054/jcaf.2002.129266 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DF UT WOS:000180263400025 PM 12555150 ER PT J AU Harding, SE Del Monte, F AF Harding, SE Del Monte, F TI Dissociation of hypertrophic growth from changes in myocyte contractile function SO JOURNAL OF CARDIAC FAILURE LA English DT Article; Proceedings Paper CT 17th World Congress of the International-Society-for-Heart-Research CY JUL 12-14, 2001 CL MINNEAPOLIS, MINNESOTA SP Int Soc Heart Res DE hypertrophy; myocyte; human; animal model ID PRESSURE-OVERLOAD HYPERTROPHY; REMODELED RAT-HEART; FAILURE AB Increases in myocyte size and impairment of contractile function are both features of the pathophysiologic hypertrophic process. In this short review, we re-present evidence, both in human disease and in animal models, that the 2 phenomena can be dissociated in both time and relative degree. Additionally, in an animal model, physiologic growth concurrent with pathophysiologic hypertrophy induces similar changes in myocyte macroarchitecture but without the deleterious consequences for contractile function. C1 Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Fac Med, London SW3 6LY, England. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Harding, SE (reprint author), Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Fac Med, Dovehouse St, London SW3 6LY, England. NR 15 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2002 VL 8 IS 6 SU S BP S415 EP S420 DI 10.1054/jcaf.2002.129252 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DF UT WOS:000180263400029 PM 12555154 ER PT J AU Huq, F DeL Monte, F Hajjar, RJ AF Huq, F DeL Monte, F Hajjar, RJ TI Modulating signaling pathways in hypertrophy and heart failure by gene transfer SO JOURNAL OF CARDIAC FAILURE LA English DT Article; Proceedings Paper CT 17th World Congress of the International-Society-for-Heart-Research CY JUL 12-14, 2001 CL MINNEAPOLIS, MINNESOTA SP Int Soc Heart Res DE gene transfer; signaling pathways; hypertrophy; heart failure ID GROWTH-FACTOR-I; ACTIVATED PROTEIN-KINASES; SARCOPLASMIC-RETICULUM CA2+-ATPASE; ADRENERGIC-RECEPTOR DESENSITIZATION; HUMAN VENTRICULAR MYOCARDIUM; RAT CARDIAC MYOCYTES; CELL-DEATH; FUNCTIONAL RELEVANCE; CALCIUM MOBILIZATION; ENHANCED EXPRESSION AB Gene transfer to the heart is a novel concept that holds great promise both as a therapeutic and an experimental tool. With the advent of improved vector technology and new insights into the pathophysiology of heart failure, it is now possible to target specific intracellular signaling pathways by adenoviral gene transfer. By over or under expressing a specific protein, complex pathways can be probed specifically, and the role of various molecular targets within crucial intracellular pathways can be more precisely defined. This review highlights recent advances made in the field of myocardial gene transfer, with an emphasis on how manipulation of signal transduction pathways by adenoviral gene transfer has been used to elucidate the pathophysiology underlying abnormal cardiac phenotypes that lead to cardiac failure, such as hypertrophy, contractile dysfunction, and apoptosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Hajjar, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St,CNY-4,4215, Charlestown, MA 02129 USA. NR 98 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2002 VL 8 IS 6 SU S BP S389 EP S400 DI 10.1054/jcaf.2002.129275 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DF UT WOS:000180263400026 PM 12555151 ER PT J AU Mann, DL AF Mann, DL TI Tumor necrosis factor-induced signal transduction and left ventricular remodeling SO JOURNAL OF CARDIAC FAILURE LA English DT Article; Proceedings Paper CT 17th World Congress of the International-Society-for-Heart-Research CY JUL 12-14, 2001 CL MINNEAPOLIS, MINNESOTA SP Int Soc Heart Res DE tumor necrosis factor; hypertrophy; remodeling; signal transduction ID NF-KAPPA-B; INDUCED CELL-DEATH; MAMMALIAN CARDIAC MYOCYTE; P55 TNF-RECEPTOR; FACTOR-ALPHA; INDUCED APOPTOSIS; TRANSGENIC MICE; CYTOCHROME-C; DILATED CARDIOMYOPATHY; INSULIN ACTION AB Recent studies have identified the importance of biologically active molecules such as neurohormones in disease progression in heart failure. More recently, it has become apparent that in addition to neurohormones another portfolio of biologically active molecules termed cytokines are also expressed in the setting of heart failure. This article will review the role of tumor necrosis factor-induced signal transduction and the process of left ventricular remodeling. C1 Houston Vet Adm Med Ctr, Winters Ctr Heart Failure Res, Cardiol Sect, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Mann, DL (reprint author), VA Med Ctr, Cardiol Res, 151C,2002 Holcombe Blvd, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [R01 HL61543-01, R01 HL58081-01, HL-42250-10/10, P50 HL-O6H] NR 77 TC 26 Z9 27 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2002 VL 8 IS 6 SU S BP S379 EP S386 DI 10.1054/jcaf.2002.129253 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DF UT WOS:000180263400024 PM 12555149 ER PT J AU Teerlink, JR AF Teerlink, JR TI Reversal of left ventricular remodeling: Role of the endothelin pathway SO JOURNAL OF CARDIAC FAILURE LA English DT Article; Proceedings Paper CT 17th World Congress of the International-Society-for-Heart-Research CY JUL 12-14, 2001 CL MINNEAPOLIS, MINNESOTA SP Int Soc Heart Res DE endothelin; heart failure; endothelin antagonists; ventricular volumes; ventricular remodeling ID EXPERIMENTAL HEART-FAILURE; REDUCES INFARCT SIZE; A RECEPTOR BLOCKADE; MYOCARDIAL-INFARCTION; ANGIOTENSIN-II; ETA-RECEPTOR; CARDIAC-FUNCTION; RAT-HEART; ANTAGONIST; BOSENTAN AB Left ventricular remodeling is the result of multiple interrelated processes that evolve through time. The contribution of neurohormones to these processes has been recognized and has lead to important therapeutic advances. Endothelin is a recently discovered neurohormone that has many properties that suggest an important role in the pathophysiology of ventricular remodeling. This review discusses this role of the endothelin pathway in the development of left ventricular remodeling and the evidence that endothelin antagonists can reverse this deleterious process. C1 San Francisco VA Med Ctr, Heart Failure Clin, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, Heart Failure Clin, 111C,4150 Clement St, San Francisco, CA 94121 USA. RI Teerlink, John/D-2986-2012 NR 39 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2002 VL 8 IS 6 SU S BP S494 EP S499 DI 10.1054/jcaf.2002.129288 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DF UT WOS:000180263400039 PM 12555164 ER PT J AU Zile, MR AF Zile, MR TI Structural components of cardiomyocyte remodeling: Summation SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material ID ACTIVATION; HEART C1 Med Univ S Carolina, Div Cardiol, Dept Med, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Zile, MR (reprint author), Med Univ S Carolina, Div Cardiol, Dept Med, Gazes Cardiac Res Inst, 96 Jonathan Lucas St,Suite 816,POB 250623, Charleston, SC 29425 USA. NR 11 TC 1 Z9 1 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2002 VL 8 IS 6 SU S BP S311 EP S313 DI 10.1054/jcaf.2002.129273 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633DF UT WOS:000180263400012 PM 12555137 ER PT J AU Mansour, M Ruskin, J Keane, D AF Mansour, M Ruskin, J Keane, D TI Initiation of atrial fibrillation by ectopic beats originating from the ostium of the inferior vena cava SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; ectopic beats ID RADIOFREQUENCY ABLATION; ELECTROPHYSIOLOGICAL CHARACTERISTICS; SUPERIOR; PULMONARY; VEINS AB Initiation of AF from IVC. Ectopic beats triggering atrial fibrillation may arise from atrial myocardial extensions in the pulmonary veins, superior vena cava, coronary sinus, and vein of Marshall. We report two patients with paroxysmal atrial fibrillation initiated by ectopic beats originating from the inferior vena cava. The foci responsible for the ectopic beats were located and ablated, resulting in elimination of atrial fibrillation. Ectopic beats originating from the os of the inferior vena cava can result in atrial fibrillation. This finding may explain the recurrence of atrial fibrillation in some patients after pulmonary vein isolation. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Keane, D (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Gray 109,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 24 Z9 24 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 DEC PY 2002 VL 13 IS 12 BP 1292 EP 1295 DI 10.1046/j.1540-8167.2002.01292.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 631CP UT WOS:000180149900016 PM 12521348 ER PT J AU Cohen, LG Prince, J Doyle, R Marcellino-Boisvert, D Wozniak, J Wilens, TE Spencer, TS Biederman, J AF Cohen, LG Prince, J Doyle, R Marcellino-Boisvert, D Wozniak, J Wilens, TE Spencer, TS Biederman, J TI Paroxetine for the treatment of depression in youth: A preliminary report SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 10-13, 2002 CL BOCA RATON, FLORIDA SP NIMH C1 Massachusetts Gen Hosp, Dept Psychiat, 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 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2002 VL 12 IS 4 BP 298 EP 298 PG 1 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 644KD UT WOS:000180915700022 ER PT J AU Goldstein, G Allen, DN Sanders, RD AF Goldstein, G Allen, DN Sanders, RD TI Sensory-perceptual dysfunction in patients with schizophrenia and comorbid alcoholism SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID NEUROLOGIC EXAMINATION ABNORMALITIES; PREVALENCE; ABUSE AB We studied the effects of aging and comorbid alcoholism on sensory-perceptual dysfunction in patients with schizophrenia. Using sensory-perceptual tests from the Halstead-Reitan Neuropsychological Battery included in the Russell, Neuringer, and Goldstein (1970) Perceptual Disorders Index, samples were compared of 54 patients with comorbid schizophrenia and alcoholism. 234 patients with schizophrenia but no history of alcoholism. 132 patients with chronic alcoholism and 171 patient controls. Data were analyzed by one-way analyses of variance followed by Scheffe multiple comparison tests. Numerous significant differences were found among groups. with the comorbid schizophrenia group doing more poorly than the other groups on measures of touch perception and suppression. finger agnosia, and fingertip number writing. Multiple regression analyses using the sensory-perceptual test, its predictor variables and age its the dependent variable indicated that the strength of association between age and the multivariate set of sensory-perceptual test scores was greater in the comorbid schizophrenia group than the noncomorbid schizophrenia, alcoholism and patient control groups. The preponderance of age-related deficits was left-sided, suggesting accelerated decline in right hemispheric function, A comparison of groups across ages on a single Perceptual Disorders Index score showed a substantially larger age effect in the comorbid schizophrenia group relative to the other groups. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Nevada, Las Vegas, NV 89154 USA. RP Goldstein, G (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, 151R,7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 20 TC 3 Z9 4 U1 1 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD DEC PY 2002 VL 24 IS 8 BP 1010 EP 1016 DI 10.1076/jcen.24.8.1010.8378 PG 7 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 642HA UT WOS:000180797100003 PM 12650227 ER PT J AU Leder, BZ Leblanc, KM Longcope, C Lee, H Catlin, DH Finkelstein, JS AF Leder, BZ Leblanc, KM Longcope, C Lee, H Catlin, DH Finkelstein, JS TI Effects of oral androstenedione administration on serum testosterone and estradiol levels in postmenopausal women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; YOUNG MEN; ESTROGEN-ANDROGEN; DEHYDROEPIANDROSTERONE SUPPLEMENTATION; SURGICAL MENOPAUSE; PROFILES; GONADOTROPIN; SECRETION; SYMPTOMS; THERAPY AB Androstenedione is a steroid hormone and an intermediate in the synthetic pathway of both testosterone and estradiol in men and women. It is available without prescription and taken with the expectation that it may have beneficial effects on strength, general well-being, libido, and quality of life. Although studies have shown that oral androstenedione increases serum testosterone and estradiol levels in men, the hormonal effects of androstenedione in postmenopausal women are unknown. We randomly assigned 30 healthy postmenopausal women to receive 0, 50, or 100 mg androstenedione as a single oral dose. After androstenedione administration, we made hourly measurements of serum androstenedione, estrone, estradiol, and testosterone concentrations during 12 h of frequent blood sampling. The mean change (+/-SD) in serum androstenedione area under the curve (AUC) was greater in both the 50-mg (79 +/- 39%) and 100-mg dose groups (242 +/- 184%) than in the control group (-29 +/- 28%) (P < 0.0001 for controls vs. 50-mg group and controls vs. 100-mg group). The mean change in serum androstenedione AUC was also greater in the 100-mg than 50-mg dose group (P = 0.0026). The mean change in serum estrone AUC was greater in both the 50-mg (108 +/- 72%) and 100-mg dose groups (116 +/- 119%) than in the control group (-5 +/- 19%), although the control vs. 100-mg group comparison did not quite meet statistical significance (P < 0.0001 for controls vs. 50-mg group, P = 0.0631 controls vs. 100-mg group). The mean change in serum estradiol AUC remained stable after supplementation in all groups without any between-group differences observed (-11 +/- 17%, 2.8 +/- 34%, -11 +/- 27%, for the control, 50-mg, and 100-mg groups, respectively). The mean change in serum testosterone AUC was greater in both the 50-mg (185 +/- 146%) and 100-mg dose groups (457 +/- 601%) than in the control group (-27 +/- 13%) (P < 0.0001 for controls vs. 50-mg group and for controls vs. 100-mg group). The mean change in testosterone AUC was also greater in the 100-mg dose group than 50-mg dose group (P = 0.0257). There was considerable individual variability in the changes of serum androstenedione, estrone, and testosterone levels in the treated groups with peak serum testosterone levels exceeding the upper limit of normal in 4 of 10 women in the 50-mg dose group and 6 of 10 in the 100-mg dose group. We concluded that the acute administration of both 50-mg and 100-mg of androstenedione increases serum testosterone and estrone levels, but not estradiol levels, in postmenopausal women. If these hormonal effects are sustained during longterm administration, regular use of this supplement by postmenopausal women could thus cause both beneficial and adverse effects. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA 01655 USA. Univ Calif Los Angeles, Dept Med, Olymp Analyt Lab, Los Angeles, CA 90025 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Olymp Analyt Lab, Los Angeles, CA 90025 USA. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Bulfinch 327,Fruit St, Boston, MA 02114 USA. EM bzleder@partners.org FU NCRR NIH HHS [RR-1066, K23-RR16310]; NIDDK NIH HHS [K24-DK02759] NR 49 TC 16 Z9 18 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2002 VL 87 IS 12 BP 5449 EP 5454 DI 10.1210/jc.2002-021035 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 628DC UT WOS:000179976300016 PM 12466335 ER PT J AU Welt, CK Taylor, AE Martin, KA Hall, JE AF Welt, CK Taylor, AE Martin, KA Hall, JE TI Serum inhibin B in polycystic ovary syndrome: Regulation by insulin and luteinizing hormone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; GONADOTROPIN-RELEASING-HORMONE; MESSENGER RIBONUCLEIC-ACIDS; GRANULOSA-LUTEAL CELLS; HUMAN MENSTRUAL-CYCLE; DIMERIC INHIBIN; DIFFERENTIAL REGULATION; ALPHA-SUBUNIT; OBESE WOMEN; ACTIVIN-A AB Inhibin B is a product of the granulosa cells of growing preantral and antral follicles. Despite the large ovarian volume and increased follicle number typically detected in women with polycystic ovary syndrome (PCOS), previous studies demonstrate that inhibin B is not elevated as would be expected in PCOS, but is inversely correlated with body mass index (BMI). We therefore hypothesized that inhibin B levels in women with PCOS are regulated by a factor related to BMI. Thus, LH, sex steroids, and metabolic parameters were measured in 50 anovulatory PCOS subjects in pools constituted from equal aliquots of serum drawn every 10 min for 4 h and were correlated with inhibin B. Based on the results of these correlative studies, inhibin B regulation by human chorionic gonadotropin (hCG) and insulin was tested directly. In PCOS subjects, inhibin B correlated inversely with BMI (r = -0.413; P < 0.004) and fasting insulin (r = -0.409; P < 0.004). Inhibin B also correlated directly with pool LH (r = 0.419; P < 0.003), LH pulse amplitude (r = 0.512; P < 0.0001), and SHBG (r = 0.429; P < 0.003). The relationships demonstrated for inhibin B were not demonstrated for inhibin A, nor were they evident in normal subjects. To determine whether the correlations represent regulation of inhibin B, i.e. stimulation of inhibin B by LH or suppression by insulin, two interventional studies were performed. In the first study hCG (5000 U) was administered to PCOS subjects (n = 15) to mimic the effects of LH. Inhibin B was not increased, but was significantly reduced 24 h after hCG administration (223.8 +/- 21.3 vs. 152.4 +/- 15.9 pg/ml; P < 0.0005). In the second study, diazoxide (100 mg every 8 h) was administered for 3 d to PCOS subjects (n = 9). Inhibin B increased (85.4 +/- 12.4 to 136.6 +/- 18.8 pg/ml; P < 0.05) in association with a decrease in the insulin area under the curve (104 +/- 29 to 83 +/- 22 nmol/liter min; P < 0.05) induced by diazoxide. In PCOS subjects, inhibin B demonstrated significant relationships with BMI and factors related to BMI, including LH, insulin, and SHBG. Although LH was associated with inhibin B, hCG administration suppressed inhibin B secretion after 24 h, whereas short-term insulin suppression increased inhibin B. These findings suggest that both increased LH and insulin may account for the relative suppression of inhibin B in patients with PCOS. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-1066]; NICHD NIH HHS [U54-HD-29164] NR 60 TC 38 Z9 40 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 DEC PY 2002 VL 87 IS 12 BP 5559 EP 5565 DI 10.1210/jc.2002-020548 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 628DC UT WOS:000179976300034 PM 12466353 ER PT J AU Klein, NA Harper, AJ Houmard, BS Sluss, PM Soules, MR AF Klein, NA Harper, AJ Houmard, BS Sluss, PM Soules, MR TI Is the short follicular phase in older women secondary to advanced or accelerated dominant follicle development? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN MENSTRUAL-CYCLE; STIMULATING-HORMONE; INHIBIN-B; LUTEINIZING-HORMONE; TRANSITION; ESTRADIOL; MENOPAUSE; DYNAMICS; RISE; AGE AB This study sought to determine whether the shortened follicular phase in ovulatory older women is secondary to advanced (i.e. earlier) or accelerated (i.e. more rapid) folliculogenesis. Normal ovulatory women, aged 40-45 yr (n = 15) and 20-25 yr (n = 13), underwent daily venipuncture and transvaginal ultrasonography throughout the follicular phase of a spontaneous menstrual cycle (control cycle) and after pituitary down-regulation with a GnRH agonist (study cycle). As expected, the older subjects in the control cycles demonstrated an elevated d 3 FSH and a shortened follicular phase compared with the younger subjects. After release from hypothalamic-pituitary-ovarian axis suppression, the early follicular phase FSH peak occurred earlier (6.8 vs. 9.8 d; P < 0.01) and was of a greater magnitude (12.1 vs. 6.5 mIU/ml; P < 0.01) in the older subjects. The time from release of suppression until the subsequent LH surge was also shorter (17.5 vs. 20.8 d; P < 0.01) in the older group. However, the time from FSH peak to LH surge was similar in the older and younger groups (10.7 vs. 11.0 d; P = 0.74). Compared with younger women, older subjects had normal follicular phase levels of estradiol and inhibin A and lower levels of inhibin B in both control and study cycles. We conclude that the shortened follicular phase observed in older ovulatory women is due to earlier dominant follicle selection, independent of hormonal influences from the preceding luteal phase. C1 Univ Washington, Div Reprod Endocrinol, Dept Obstet & Gynecol, Seattle, WA 98105 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Klein, NA (reprint author), Univ Washington, Div Reprod Endocrinol, Dept Obstet & Gynecol, 4225 Roosevelt Way NE,Suite 305, Seattle, WA 98105 USA. EM nklein@u.washington.edu FU NIA NIH HHS [R01-AG-14579]; NICHD NIH HHS [U54-HD29164] NR 29 TC 64 Z9 66 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 DEC PY 2002 VL 87 IS 12 BP 5746 EP 5750 DI 10.1210/jc.2002-020622 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 628DC UT WOS:000179976300060 PM 12466381 ER PT J AU Atkinson, MA Wilson, SB AF Atkinson, MA Wilson, SB TI Fatal attraction: chemokines, and type 1 diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID NOD MICE; RECEPTOR; MELLITUS; CELLS C1 Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Atkinson, MA (reprint author), Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, ARB-R3-128,1600 SW Archer Rd, Gainesville, FL 32610 USA. NR 19 TC 18 Z9 22 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2002 VL 110 IS 11 BP 1611 EP 1613 DI 10.1172/JCI200217311 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 623ME UT WOS:000179706500007 PM 12464665 ER PT J AU Limbourg, FP Huang, ZH Plumier, JC Simoncini, T Fujioka, M Tuckermann, J Schutz, G Moskowitz, MA Liao, JK AF Limbourg, FP Huang, ZH Plumier, JC Simoncini, T Fujioka, M Tuckermann, J Schutz, G Moskowitz, MA Liao, JK TI Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HIGH-DOSE METHYLPREDNISOLONE; SPINAL-CORD INJURY; GLUCOCORTICOID RECEPTOR; ESTROGEN-RECEPTOR; SURVIVAL SIGNALS; INFARCT VOLUME; GROWTH-FACTOR; KINASE SGK; L-ARGININE; CELLS AB Many cellular responses to corticosteroids involve the transcriptional modulation of target genes by the glucocorticoid receptor (GR). A rapid, non-nuclear effect of GR was found to mediate neuroprotection. High-dose corticosteroids (20 mg/kg intraperitoneally), given within 2 hours of transient cerebral ischemia, acutely increased endothelial nitric oxide synthase (eNOS) activity, augmented regional cerebral blood flow (CBF) by 40% to 50%, and reduced cerebral infarct size by 32%. These neuroprotective effects of corticosteroids were abolished by the GR antagonist RU486 and by inhibition of phosphatidylinositol 3-kinase (PI3K), and were absent in eNOS(-/-) mice. To determine the mechanism by which GR activated eNOS, we measured the effect of corticosteroids on PI3K and the protein kinase Akt. In a ligand-dependent manner, GR activated PI3K and Akt in vitro and in vivo caused NO-dependent vasodilation, which was blocked by cotreatment with RU486 or the PI3K inhibitor LY294002 but not by transcriptional inhibitors. Indeed, a mutant GR, which cannot dimerize and bind to DNA, still activated PI3K and Akt in response to corticosteroids. These findings indicate that non-nuclear GR rapidly activates eNOS through the PI3K/Akt pathway and suggest that this mechanism mediates the acute neuroprotective effects of corticosteroids through augmentation of CBF. C1 Brigham & Womens Hosp, Div Cardiovasc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Lab Stroke & Neurovasc Regulat, Boston, MA 02114 USA. Univ Pisa, Dept Reprod Med & Child Dev, Pisa, Italy. German Canc Res Ctr, Dept Mol Biol Cell 1, D-6900 Heidelberg, Germany. RP Liao, JK (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 65 Landsdowne St,Room 275, Cambridge, MA 02139 USA. RI Moskowitz, Michael/D-9916-2011; OI Simoncini, Tommaso/0000-0002-2971-0079 FU NHLBI NIH HHS [HL-48743, HL-52233, HL-70274, P01 HL048743, R01 HL052233, R01 HL070274]; NINDS NIH HHS [F32 NS010828, NS-10828, P01 NS010828, P50 NS010828] NR 57 TC 147 Z9 152 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2002 VL 110 IS 11 BP 1729 EP 1738 DI 10.1172/CJI200215481 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 623ME UT WOS:000179706500020 PM 12464678 ER PT J AU Kitamura, T Nakae, J Kitamura, Y Kido, Y Biggs, WH Wright, CVE White, MF Arden, KC Accili, D AF Kitamura, T Nakae, J Kitamura, Y Kido, Y Biggs, WH Wright, CVE White, MF Arden, KC Accili, D TI The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NUCLEAR FACTOR 3-BETA; RECEPTOR; EXPRESSION; GENE; MICE; DISRUPTION; SURVIVAL; PROTEIN; ISLETS; TISSUE AB Diabetes is caused by an absolute (type 1) or relative (type 2) deficiency of insulin-producing beta cells. The mechanisms governing replication of terminally differentiated beta cells and neogenesis from progenitor cells are unclear. Mice lacking insulin receptor substrate-2 (Irs2) develop beta cell failure, suggesting that insulin signaling is required to maintain an adequate beta cell mass. We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. C1 Columbia Univ Coll Phys & Surg, Dept Med, Naomi Berrie Diabet Ctr, New York, NY 10032 USA. Univ Calif San Diego, Ludwig Inst Canc Res, San Diego, CA 92103 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Accili, D (reprint author), Berrie Res Pavil,1150 St Nicholas Ave,Room 238A, New York, NY 10032 USA. FU NIDDK NIH HHS [DK-57539, R01 DK057539] NR 38 TC 362 Z9 376 U1 0 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2002 VL 110 IS 12 BP 1839 EP 1847 DI 10.1172/JCI200216857 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 626YJ UT WOS:000179901100013 PM 12488434 ER PT J AU Harper, CG Feng, Y Xu, S Taylor, NS Kinsel, A Dewhirst, FE Paster, BJ Greenwell, M Levine, G Rogers, A Fox, JG AF Harper, CG Feng, Y Xu, S Taylor, NS Kinsel, A Dewhirst, FE Paster, BJ Greenwell, M Levine, G Rogers, A Fox, JG TI Helicobacter cetorum sp nov., a urease-positive Helicobacter species isolated from dolphins and whales SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GASTRIC-ULCER; HUMAN FECES; PYLORI; MUSTELAE; PCR; FERRETS; TRANSMISSION; ASSOCIATION; PHYLOGENY; BACTERIA AB A novel helicobacter with the proposed name Helicobacter cetorum, sp. nov. (type strain MIT 99-5656; GenBank accession number AF 292378), was cultured from the main stomach of two wild, stranded Atlantic white-sided dolphins (Lagenorhynchus acutus) and from the feces of three captive cetaceans (a Pacific white-sided dolphin [Lagenorhynchus obliquidens]; an Atlantic bottlenose dolphin [Tursiops truncatus]; and a beluga whale [Delphinapterus leucas]). The infected captive cetaceans were either subclinical, or clinical signs included intermittent regurgitation, inappetance, weight loss, and lethargy. Ulcers were observed in the esophagus and forestomach during endoscopic examination in two of the three captive animals. In the third animal, esophageal linear erosions were visualized endoscopically, and histopathological evaluation of the main stomach revealed multifocal lymphoplasmacytic gastritis with silver-stained spiral-shaped bacteria. Helicobacter cetorum is a fusiform gram-negative bacterium with a single bipolar flagellum. The isolates grow under microaerobic conditions at 37 and 42degreesC but not at 25degreesC. H. cetorum is urease, catalase, and oxidase positive, and it is sensitive to cephalothin. The isolates from the wild, stranded dolphins were sensitive to nalidixic acid, whereas the isolates from the collection animals were resistant. By 16S rRNA sequencing it was determined that H. cetorum represented a distinct taxon that clusters most closely with H. pylori. Further studies are necessary to determine the role of H. cetorum in the development of gastric ulcers and gastritis of cetaceans. This is the first description and formal naming of a novel Helicobacter species from a marine mammal. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Univ Illinois, Zool Pathol Program, Maywood, IL 60153 USA. Dolphin Quest, Oahu, HI 96795 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Rm 825C, Cambridge, MA 02139 USA. FU NCRR NIH HHS [T32 RR007036, T32-RR07036]; NIAID NIH HHS [R01-AI37750, R01 AI037750]; NIDCR NIH HHS [R01 DE010374, R01-DE10374] NR 40 TC 48 Z9 49 U1 0 U2 3 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 DEC PY 2002 VL 40 IS 12 BP 4536 EP 4543 DI 10.1128/JCM.40.12.4536-4543.2002 PG 8 WC Microbiology SC Microbiology GA 622DP UT WOS:000179631500022 PM 12454148 ER PT J AU Lipshultz, SE Lipsitz, SR Sallan, SE Simbre, VC Shaikh, SL Mone, SM Gelber, RD Colan, SD AF Lipshultz, SE Lipsitz, SR Sallan, SE Simbre, VC Shaikh, SL Mone, SM Gelber, RD Colan, SD TI Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEART-FAILURE; CARDIOTOXICITY; MORTALITY; CHILDREN; HYPERTENSION; HYPERTROPHY; INHIBITOR; ADULTS AB Purpose: A common late effect of doxorubicin therapy for childhood cancer is reduced left-ventricular (LV) wall thickness resulting in elevated LV afterload and depressed LV function. Many children are given angiotensin-converting enzyme inhibitors, which have been studied primarily in adults. We document the long-term effects of angiotensin-converting enzyme inhibitors in doxorubicin-treated survivors of childhood cancer. Patients and Methods: In this retrospective study, we reviewed records of 18 children who had regular echocardiographic examinations during enalapril therapy (mean age at cancer diagnosis, 8 years; mean time between completion of doxorubicin therapy and start of enalapril, 7 years; median follow-up since the start of enalapril, 10 years). Results: Over the first 6 years of enalapril therapy, there was progressive improvement toward normal values in LV dimension, afterload, fractional shortening, and mass, but all these parameters deteriorated between 6 and 10 years. LV wall thickness deteriorated throughout the study period, as did LV contractility and systolic blood pressure. Diastolic blood pressure fell slightly. By 6 years on enalapril, all six patients who had had congestive heart failure at the start of enalapril therapy had either died or undergone cardiac transplantation, compared with three of the 12 asymptomatic patients. Conclusion: In doxorubicin-treated long-term survivors of childhood cancer, enalapril-induced improvement in LV structure and function is transient. The primary defect, which is LV wall thinning, continues to deteriorate, and thus the short-term improvement was mostly related to lowered diastolic blood pressure. (C) 2002 by American Society of Clinical Oncology. C1 Univ Rochester, Med Ctr, Div Pediat Cardiol, Rochester, NY 14642 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. Golisano Childrens Hosp Strong, Rochester, NY USA. James P Wilmot Canc Ctr, Rochester, NY USA. RP Lipshultz, SE (reprint author), Univ Rochester, Med Ctr, Div Pediat Cardiol, 601 Elmwood Ave,Box 631, Rochester, NY 14642 USA. FU NCI NIH HHS [CA 55576, CA 06516, CA 68484, CA 79060]; NHLBI NIH HHS [HL 59837, HL 53392, HR 96041] NR 28 TC 128 Z9 133 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2002 VL 20 IS 23 BP 4517 EP 4522 DI 10.1200/JCO.2002.12.102 PG 6 WC Oncology SC Oncology GA 622DX UT WOS:000179632200003 PM 12454107 ER PT J AU D'Amico, AV Cote, K Loffredo, M Renshaw, AA Schultz, D AF D'Amico, AV Cote, K Loffredo, M Renshaw, AA Schultz, D TI Determinants of prostate cancer-specific survival after radiation therapy for patients with clinically localized prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; DISEASE RECURRENCE; ANTIGEN; RADIOTHERAPY; FAILURE; PROGRESSION; NOMOGRAM; TRIALS; MEN AB Purpose: Identifying pretreatment and posttreatment predictors of time to prostate cancer-specific death (PCSD) after external-beam radiation therapy (RT) was the subject of this study. Patients and Methods: A Cox regression analysis was used to evaluate the ability of the pretreatment risk group to predict time to PCSD for 381 patients who underwent RT for clinically localized prostate cancer. Posttreatment factors analyzed for the 94 patients who experienced prostate-specific antigen (PSA) failure included the time to PSA failure, the posttreatment PSA doubling time (DT), and the timing of salvage hormonal therapy. Results: Despite the median age of 73 years at diagnosis, 45% of patients with high-risk disease were estimated to die from prostate cancer within 10 years after RT compared with 0% (P = .004) and 6% (P = .05) for patients with low- or intermediate-risk disease, respectively. Predictors of time to PCSD after PSA failure included PSA DT (P = .01) and delayed use of hormonal therapy (P less than or equal to .002). Nearly identical estimates of PCSD and all-cause death after PSA failure were noted for patients with a short PSA DT (ie, less than or equal to 12 months). Conclusion: Prostate cancer was a major cause of death during the first decade after RT for patients with clinically localized but high-risk disease, and the cause of death for patients with a short PSA DT after RT was nearly always prostate cancer. These data provide evidence to propose the hypothesis that a short posttreatment PSA DT may serve as a possible surrogate for PCSD. Prospective validation is needed. (C) 2002 by American Society of Clinical Oncology. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. NR 25 TC 170 Z9 173 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2002 VL 20 IS 23 BP 4567 EP 4573 DI 10.1200/JCO.2002.03.061 PG 7 WC Oncology SC Oncology GA 622DX UT WOS:000179632200010 PM 12454114 ER PT J AU Chapple, ILC Brock, G Eftimiadi, C Matthews, JB AF Chapple, ILC Brock, G Eftimiadi, C Matthews, JB TI Glutathione in gingival crevicular fluid and its relation to local antioxidant capacity in periodontal health and disease SO JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY LA English DT Article ID PERIPHERAL NEUTROPHILS; ADULT PERIODONTITIS; CHEMILUMINESCENCE; STIMULATION; RADICALS; SERUM; CELLS; LUNG AB Aims: To determine possible changes in gingival crevicular fluid (GCF) antioxicant defence in chronic adult periodontal disease and to investigate the nature of the local radical scavenging mechanisms, with particular reference to glutathione. Methods: GCF and plasma were collected from patients with chronic periodontitis and age and sex matched control subjects (n = 10). Polymorphonuclear leucocytes (PMNLs) were prepared and gingival epithelial cells (GECs) were collected by conventional methods from periodontally healthy subjects. PMNL were stimulated with F-Met-Leu-Phe after cytochalasin B treatment. Enhanced chemiluminescence was used to determine the total antioxidant capacity and to investigate the activity of cell fractions and reducing agents. GCF concentrations of reduced (GSH) and oxidised (GSSG) glutathione were determined by high performance liquid chromatography. Results: Plasma and GCF from patients contained lower mean (SD) total antioxidant capacity (501.8 (123) muM Tec/litre and 658.3 (392) muM Tec/litre, respectively) compared with controls (577.9 (99.8) and 1351.5 (861) muM Tec/litre, respectively). Antioxidant light recovery profiles for GCF demonstrated a stepped response, not seen in plasma, which was inhibited by N-ethylmaleimide. This response was also detected in the cytosolic fraction of GEC and anaerobically stimulated PMNL. Similar antioxicant profiles, inhibitable by N-ethylmaleimide, were obtained with cysteamine, cysteine, and GSH. Control GCF contained high mean (SD) concentrations of glutathione (GSH, 1899.8 (494.4)muM; GSSG, 256.8 (152.4)muM). GCF from patients with periodontitis contained significantly lower amounts of GSH (mean, 1183.1; SD, 580.3muM) and GSSG (mean, 150.1; SD, 44.9muM). Conclusions: GSH values and total antioxicant capacity are reduced in chronic periodontal disease. The high concentrations of GSH present in GCF in health are similar to those found extracellularly in the lung and may represent an important antioxidant and anti-inflammatory defence strategy common to exposed epithelial surfaces. C1 Univ Birmingham, Unit Periodontol, Sch Dent, Birmingham B4 6NN, W Midlands, England. Forsyth Res Ctr, Boston, MA USA. Univ Birmingham, Unit Oral Pathol & Biol, Sch Dent, Birmingham B15 2TT, W Midlands, England. RP Chapple, ILC (reprint author), Univ Birmingham, Unit Periodontol, Sch Dent, St Chads Queensway, Birmingham B4 6NN, W Midlands, England. RI Eftimiadi, Costantino/F-3491-2015 OI Eftimiadi, Costantino/0000-0003-1510-4614 NR 31 TC 61 Z9 64 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1366-8714 J9 J CLIN PATHOL-MOL PA JI J. Clin. Pathol.-Mol. Pathol. PD DEC PY 2002 VL 55 IS 6 BP 367 EP 373 PG 7 WC Pathology SC Pathology GA 625AZ UT WOS:000179795800004 PM 12456773 ER PT J AU Zhang, J Kashket, S Lingstrom, P AF Zhang, J Kashket, S Lingstrom, P TI Evidence for the early onset of gingival inflammation following short-term plaque accumulation SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE chlorhexidine; crevicular fluid; gingivitis; IL-1b; IL-8; inflammation; plaque accumulation; polymorphonuclear leukocytes; tooth brushing ID CREVICULAR FLUID; DISEASE; ALPHA AB Aim: A study was undertaken to examine cytokine markers in gingival crevicular fluid (GCF) during the early stages of plaque accumulation. Methods: A panel of five subjects with good oral hygiene went without brushing for 1 or 3 days, after which GCF samples were taken by placing paper strips into the gingival margins of the maxillary premolars and first molar for 30 s. GCF flow rates were determined with a Periotron(R) instrument (Oraflow, Inc., Plainview, New York), and neutrophils (polymorphonuclear leukocytes) were determined as myeloperoxidase activity. Interleukin-1b (IL-1b) and IL-8 were eluted from the paper strips and assayed with enzyme-linked immunosorbent assay (ELISA) systems. Results: The plaque index rose to 2.7 +/- 0.2 (mean +/- SE) after 3 days without brushing, and the GCF flow rate increased to 146.8% of baseline. PMN and IL-8 concentrations fell but, when corrected for dilution as a result of increased GCF flow, were not statistically different from baseline. IL-1b was slightly elevated after 1 day, and increased to 223.8 +/- 54.3% (from 6.8 +/- 1.7 to 13.8 +/- 3.6 pg/30 s; p = 0.04) after 3 days of plaque accumulation. Resumption of tooth brushing led to a return of IL-1b to baseline (109.1% after 2 days of brushing). When subjects rinsed with 0.12% chlorhexidine during the 3-day no-brushing period, the increases in plaque index, GCF flow rates and IL-1b release rates did not occur. Conclusions: The results indicate that IL-1b release rates increase in the GCF after 3 days of plaque accumulation, before any clinical signs of inflammation appear. C1 Univ Gothenburg, Inst Odontol, Dept Cariol, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden. Forsyth Inst, Nutr Sect, Boston, MA USA. RP Lingstrom, P (reprint author), Univ Gothenburg, Inst Odontol, Dept Cariol, Sahlgrenska Acad, Box 450, SE-40530 Gothenburg, Sweden. NR 12 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL MUNKSGAARD 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 DEC PY 2002 VL 29 IS 12 BP 1082 EP 1085 DI 10.1034/j.1600-051X.2002.291206.x PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 630QK UT WOS:000180119500006 PM 12492908 ER PT J AU Tew, JD Mulsant, BH Haskett, RF Dolata, D Hixson, L Mann, JJ AF Tew, JD Mulsant, BH Haskett, RF Dolata, D Hixson, L Mann, JJ TI A randomized comparison of high-charge right unilateral electroconvulsive therapy and bilateral electroconvulsive therapy in older depressed patients who failed to respond to 5 to 8 moderate-charge right unilateral treatments SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ELECTRODE PLACEMENT; MAJOR DEPRESSION; EFFICACY; ECT; ANTIDEPRESSANT AB Background: Electroconvulsive therapy (ECT) is the treatment of choice in some older patients with severe depression. When compared with younger depressed patients, older patients have been shown to be as likely to respond to ECT but more likely to develop cognitive impairment. This study addresses whether adults aged 50 years and over who have already failed to respond to at least 5 moderate-charge right unilateral (RUL) ECT treatments (150% above seizure threshold) are more likely to benefit from a switch to high-charge RUL ECT (450% above threshold) or to bilateral (BL) ECT. Method: Twenty-four patients who were treated with 5 to 8 moderate-charge RUL ECT treatments and who failed to improve sufficiently were randomly assigned to receive either BL ECT (N = 11) or high-charge RUL ECT (N = 13). Depressive (24-item Hamilton Rating Scale for Depression) and cognitive scores (Mini-Mental State Examination [MMSE]) were compared under double-blind conditions at 3 phases of treatment. Results: Patients in the BL ECT group exhibited significantly greater cognitive impairment (mean MMSE score decrease of 1.13) than those receiving high-charge RUL ECT (mean MMSE increase of 1.71). There were no statistically significant differences in clinical response to BL or high-charge RUL ECT (63.6% and 61.5%, respectively) or in depressive symptom remission (18.1% and 46.2%). Conclusion: These results suggest that older patients who fail to respond to moderate-charge RUL ECT may benefit from a switch to high-charge RUL ECT rather than BL ECT. Larger future studies will be needed to compare clinical response in patients switched from moderate-dose RUL ECT to higher-dose RUL or to BL ECT. C1 Univ Pittsburgh, Sch Med, WPIC, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. RP Mulsant, BH (reprint author), Univ Pittsburgh, Sch Med, WPIC, Dept Psychiat, E837,3811 O Hara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH01613, MH30915, MH48512, MH52247, MH61591] NR 13 TC 15 Z9 18 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2002 VL 63 IS 12 BP 1102 EP 1105 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 635QK UT WOS:000180410200003 PM 12523868 ER PT J AU Spencer, T Heiligenstein, JH Biederman, J Faries, DE Kratochvil, CJ Conners, CK Potter, WZ AF Spencer, T Heiligenstein, JH Biederman, J Faries, DE Kratochvil, CJ Conners, CK Potter, WZ TI Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; DESIPRAMINE AB Background: Atomoxetine is a nonstimulant drug being studied for the treatment of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a highly specific inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors. Results of 2 proof-of-concept studies are reported that tested the hypothesis that a selective inhibitor of presynaptic norepinephrine uptake would be effective for the treatment of ADHD in school-aged children. Method: Two identical 12-week, stratified, randomized, double-blind, placebo-controlled trials were conducted in children who met DSM-IV criteria for ADHD. The primary efficacy outcome measure was the mean change from baseline to endpoint in the Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD RS) total score. Secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and the Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S). Results: A total of 291 patients were randomized in the 2 trials combined (Study 1, N = 147; Study 2, N = 144). Stimulant-naive patients were randomized to atomoxetine, placebo, or methylphenidate. Patients with prior stimulant exposure were randomized to atomoxetine or placebo. Atomoxetine significantly reduced ADHD RS total scores compared with placebo in each study (p < .001). Changes in the CGI-ADHD-S (Study 1: p = .003; Study 2: p = .001) and CPRS-ADHD Index (Study 1: p = .023; Study 2: p < .001) also showed atomoxetine to be statistically significantly superior to placebo in reducing ADHD symptoms. Atomoxetine was found to be well tolerated in this population of pediatric patients. Conclusion: Two studies of atomoxetine early in its development confirmed that atomoxetine, a specific and selective inhibitor of noradrenergic uptake, was effective for the treatment of children with ADHD. In addition, atomoxetine was found to be well tolerated. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. RP Heiligenstein, JH (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Drop Code 1730, Indianapolis, IN 46285 USA. NR 31 TC 204 Z9 207 U1 8 U2 15 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2002 VL 63 IS 12 BP 1140 EP 1147 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 635QK UT WOS:000180410200009 PM 12523874 ER PT J AU Zajecka, JM Weisler, R Sachs, G Swann, AC Wozniak, P Sommerville, KW AF Zajecka, JM Weisler, R Sachs, G Swann, AC Wozniak, P Sommerville, KW TI A comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 09-14, 2000 CL SAN JUAN, PUERTO RICO SP Amer Coll Neuropsychopharmacol ID ACUTE MANIA; DIABETIC-KETOACIDOSIS; DOUBLE-BLIND; PLACEBO; ANTIPSYCHOTICS; LITHIUM; HYPERGLYCEMIA; EPIDEMIOLOGY; VALPROATE; MELLITUS AB Background: This study compared the efficacy, safety, and tolerability of divalproex and olanzapine in the treatment of acute mania associated with bipolar disorder. Method: This randomized, 12-week, double-blind, parallel-group, multicenter study included DSM-IV-defined bipolar disorder type I patients hospitalized for acute mania and randomly assigned to treatment with divalproex or olanzapine. After an inpatient period of up to 21 days, subjects were followed as outpatients. Dose adjustment was permitted during the inpatient period. Efficacy was assessed using change from baseline in Mania Rating Scale (MRS) score to day 21; other efficacy measures included the Brief Psychiatric Rating Scale, the Hamilton Rating Scale for Depression, and the Clinical Global Impressions-Part 1, Severity of Illness scale. The primary safety endpoint was change from baseline in weight. Other safety and tolerability endpoints included spontaneous adverse event reporting and changes from baseline in laboratory measures and vital signs. Results: 120 subjects (N = 63 divalproex, N = 57 olanzapine) were randomly assigned to treatment. No significant differences between groups were found for any efficacy variable for change from baseline to day 21. Mean MRS score changes from baseline to day 21 were -14.8 for divalproex and -17.2 for olanzapine (p = .210). A significantly (p < .05) greater proportion of olanzapine-treated subjects experienced somnolence, weight gain, edema, rhinitis, and speech disorder (slurred speech); no adverse events were significantly greater in the divalproex group. A number of laboratory measures also demonstrated significant treatment differences, but the clinical significance of many of these is uncertain. Mean body weight changes were significantly greater in the olanzapine group (+ 8.8 lb [+ 4.0 kg]) than the divalproex group (+ 5.5 lb [+ 2.5 kg], p < .050). One death occurred during the study (olanzapine group, diabetic ketoacidosis). Conclusion: No significant difference in efficacy was found between treatment groups. Divalproex was associated with a more favorable adverse event profile and significantly less weight gain than olanzapine. C1 Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Holy Hill Hosp, Raleigh, NC USA. Duke Univ, Durham, NC 27706 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Zajecka, JM (reprint author), Rush Presbyterian St Lukes Med Ctr, 1725 W Harrison St,Suite 955, Chicago, IL 60612 USA. NR 33 TC 132 Z9 134 U1 3 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2002 VL 63 IS 12 BP 1148 EP 1155 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 635QK UT WOS:000180410200010 PM 12523875 ER PT J AU Matthews, JD Bottonari, KA Polania, LM Mischoulon, D Dording, CM Irvin, R Fava, M AF Matthews, JD Bottonari, KA Polania, LM Mischoulon, D Dording, CM Irvin, R Fava, M TI An open study of olanzapine and fluoxetine for psychotic major depressive disorder: Interim analyses SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 153rd Annual Meeting of the American-Psychiatric-Association CY MAY 13-18, 2000 CL CHICAGO, ILLINOIS SP Amer Psychiat Assoc ID DELUSIONAL DEPRESSION; ELECTROCONVULSIVE-THERAPY; UNIPOLAR DEPRESSION; SEPARATE ENTITY; DRUG RESPONSE; DOUBLE-BLIND; RISPERIDONE; CLOZAPINE; FEATURES; AMITRIPTYLINE AB Background: Although atypical antipsychotic agents are commonly used in the treatment of psychotic depression, there are no published prospective studies on their use in this condition. The aim of this study was to assess, by interim analyses, the efficacy of the atypical antipsychotic agent olanzapine in combination with the selective serotonin reuptake inhibitor antidepressant agent fluoxetine. Method: We enrolled 27 patients (17 women [63.0%] and 10 men [37.0%]; mean +/- SD age: 41.2 +/- 14.7 years) with DSM-IV-defined major depressive disorder with psychotic features into an open trial of olanzapine, 5 to 20 mg/day, plus fluoxetine 20 to 80 mg/day. Patients were assessed at each visit with the 17-item Hamilton Rating Scale for Depression and both the psychotic and mood modules of the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition. We are reporting the results of the first 6 weeks of treatment. Results: Twenty-two (81.5%) of the 27 enrolled patients completed the 6-week open trial, and 5 (18.5%) dropped out, with only 2 (7.4%) dropping out due to side effects. Of the 27 patients, 74.1% (N = 20) met criteria for melancholic features, 14.8% (N = 4) had delusions alone, 18.5% (N = 5) had hallucinations alone, and 66.7% (N = 18) reported both delusions and hallucinations. In addition, the overall rates of response for the intent-to-treat group were as follows: depression response rate, 66.7% (N = 18); psychosis response rate, 59.3% (N = 16); psychotic depression response rate, 55.6% (N = 15); and psychotic depression remission rate, 40.7% (N = 11). Conclusion: The combination of olanzapine and fluoxetine appears to be a promising, safe, and effective treatment for psychotic depression. Double-blind studies are needed to confirm this impression. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Matthews, JD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 54 TC 35 Z9 36 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2002 VL 63 IS 12 BP 1164 EP 1170 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 635QK UT WOS:000180410200012 PM 12523877 ER PT J AU Heber, R Kellner, M Yehuda, R AF Heber, R Kellner, M Yehuda, R TI Salivary cortisol levels and the cortisol response to dexamethasone before and after EMDR: A case report SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE EMDR; dexamethasone suppression test; cortisol; posttraumatic stress disorder; neuroendocrine ID EYE-MOVEMENT DESENSITIZATION; POSTTRAUMATIC-STRESS-DISORDER; SUPPRESSION; WOMEN AB Trauma survivors with posttraumatic stress disorder (PTSD) have been shown to have lower basal cortisol levels in the urine, plasma, and saliva than in trauma survivors without PTSD, nontraurnatized mentally ill. or healthy subjects. We report on a case study in which we measured pre and post-Eye Movement Desensitization and Reprocessing (EMDR) treatment salivary cortisol levels and salivary cortisol response to 0.50 mg of dexamethasone in a 41-year-old female with chronic PTSD symptoms. Our goal was to determine whether symptom improvement following trauma-focused treatment (EMDR) is associated with changes in basal salivary cortisol or in the cortisol response to dexamethasone administration. Our findings show moderate symptom improvement, an increase in basal cortisol levels, and a more attenuated cortisol hypersuppression in response to the dexamethasone suppression test following EMDR treatment. These results suggest the potential utility of including neuroendocrine measures in the assessment of treatment outcome in PTSD. (C) 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1521-1530, 2002. C1 CUNY Mt Sinai Sch Med, Bronx, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. RP Heber, R (reprint author), 200 E 33rd St,Apt 4-I, New York, NY 10016 USA. FU PHS HHS [R01 49536, R01 49555] NR 27 TC 14 Z9 14 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD DEC PY 2002 VL 58 IS 12 BP 1521 EP 1530 DI 10.1002/jclp.10102 PG 10 WC Psychology, Clinical SC Psychology GA 622EH UT WOS:000179633200006 PM 12455019 ER PT J AU Wilens, TE Cohen, L Biederman, J Abrams, A Neft, D Faird, N Sinha, V AF Wilens, TE Cohen, L Biederman, J Abrams, A Neft, D Faird, N Sinha, V TI Fluoxetine pharmacokinetics in pediatric patients SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; POPULATION PHARMACOKINETICS; SERUM CONCENTRATIONS; DEPRESSED CHILDREN; DRUG-INTERACTIONS; CONTROLLED TRIAL; DOUBLE-BLIND; ADOLESCENTS; DESIPRAMINE; PLACEBO AB The objective of this study was to evaluate the pharmacokinetic profile of fluoxetine (FLX) and its major metabolite, norfluoxetine (NORFLX), in children and adolescent patients undergoing psychiatric treatment. Twenty-one pediatric subjects-10 children (6-12 years) and 11 adolescents (13-18 years)-were administered 20 mg FLX for 60 days, with sparse blood samples taken throughout the open-label study. Subjects contributed 168 plasma concentrations. Pharmacokinetic parameters were estimated using a mixed effects nonlinear model. Mean steady-state FLX and NORFLX of 12 7 ng/mL and 151 ng/mL, respectively, were achieved in children and adolescents after 4 weeks of treatment, with high between-patient variability. FLX was 2-fold higher and NORFLX was 1.7-fold higher in children relative to adolescents; however, when normalized to body weight, FLX and NORFLX were similar for both age groups. Age, body weight, body mass index, and body surface area, modeled independently as continuous variables, significantly improved the population pharmacokinetic model when evaluated as patient factors. Body weight was the covariate retained in the final model. In conclusion, children have 2-fold higher FLX and NORFLX relative to adolescents that appear to be related to indices of body size. The accumulation profile and steady-state concentrations in adolescents appear similar to those in adults. C1 Harvard Univ, Pediat Psychopharmacol Unit, Massachusetts Gen Hosp, Sch Med,Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Lilly Lab Clin Res, Indianapolis, IN USA. RP Wilens, TE (reprint author), Harvard Univ, Pediat Psychopharmacol Unit, Massachusetts Gen Hosp, Sch Med,Clin Res Program Pediat Psychopharmacol, ACC 725,15 Parkman St, Boston, MA 02114 USA. NR 37 TC 38 Z9 38 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2002 VL 22 IS 6 BP 568 EP 575 DI 10.1097/00004714-200212000-00006 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 622GW UT WOS:000179639500006 PM 12454556 ER PT J AU Venkataraman, R Kellum, JA Palevsky, P AF Venkataraman, R Kellum, JA Palevsky, P TI Dosing patterns for continuous renal replacement therapy at a large academic medical center in the United States SO JOURNAL OF CRITICAL CARE LA English DT Article ID CONTINUOUS HEMOFILTRATION; DELIVERED DIALYSIS; FAILURE; HEMODIALYSIS; MEMBRANES; MULTICENTER; OUTCOMES; CHOICE; TRIAL AB Purpose: We sought to retrospectively review the dosing patterns of continuous renal replacement therapy (CRRT) in patients with acute renal failure (ARF) and determine their actual delivered dosage of CRRT. Materials and Methods: Computerized records of patients (n = 115) who received CRRT for ARF at a single, large, academic, tertiary care hospital from September 1, 1999 through August 31, 2000 were reviewed. The delivered dose of CRRT for each patient/day was calculated from the hourly effluent flow rate, the patient's weight, and the duration (in hours) of CRRT for that day. A mean effluent flow rate (in L/h) for each patient was then calculated. Results: The average number of hours/day on CRRT was 16.1 +/- 3.53 (mean +/- SD), with a mean flow rate (averaged over 24 h) of 1.36 +/- 0.31 L/h. The mean CRRT dose prescribed for these patients was 24.46 +/- 6.13 mL/Kg/h, but the mean dose delivered was only 16.55 +/- 5.41 mL/Kg/h (68% of the prescribed dose, P < .000001). Conclusions: Many patients are prescribed low doses of CRRT Furthermore, the dose delivered is considerably lower than that prescribed. Methods and procedures to extend CRRT system life may improve the dose delivery. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Kellum, JA (reprint author), Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Lab, 3550 Terrace St, Pittsburgh, PA 15261 USA. OI Palevsky, Paul/0000-0002-7334-5400 NR 28 TC 59 Z9 63 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 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD DEC PY 2002 VL 17 IS 4 BP 246 EP 250 DI 10.1053/jcrc.2002.36757 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 627UB UT WOS:000179953600006 PM 12501152 ER PT J AU Chuang, SK Tian, L Wei, LJ Dodson, TB AF Chuang, SK Tian, L Wei, LJ Dodson, TB TI Predicting dental implant survival by use of the marginal approach of the semi-parametric survival methods for clustered observations SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE survival predictions; dental implants; clustered data; correlated survival analysis; proportional hazards model; marginal approach; Aalen-Breslow estimator ID FAILURE TIME DATA; PROSPECTIVE MULTICENTER; TRANSFORMATION MODELS; REGRESSION-ANALYSIS; ITI-IMPLANTS; STRATEGY; RATES AB The analyses of clustered survival observations within the same subject are challenging. This study's purpose was to compare and contrast predicted dental implant survival estimates assuming the independence or dependence of clustered observations. Using a retrospective cohort composed of 677 patients (2349 implants), we applied an innovative analytic marginal approach to produce point and variance estimates of survival predictions given the covariates smoking status, implant staging, and timing of placement adjusted for clustered observations (dependence method). We developed a second model assuming independence of the clustered observations (naive method). The 95% confidence intervals for survival prediction point estimates given the naive method were 5.9% to 14.3% more narrow than the dependence method estimates, resulting in an increased risk for type I error and erroneous rejection of the null hypothesis. To obtain statistically valid confidence intervals for survival prediction of the Aalen-Breslow estimates, we recommend adjusting for dependence among clustered survival observations. C1 Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Chuang, SK (reprint author), POB 67376,Chestnut Hill Stn, Chestnut Hill, MA 02467 USA. EM schuang@hsph.harvard.edu FU NCI NIH HHS [R01 CA56844]; NIDCR NIH HHS [K16 DE000275, K24 DE000448] NR 25 TC 44 Z9 45 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 IS 12 BP 851 EP 855 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 620WJ UT WOS:000179555900012 PM 12454101 ER PT J AU Al Mutawa'a, S Al Duwairy, Y DePaola, PF Udani, TM Soparkar, PM AF Al Mutawa'a, S Al Duwairy, Y DePaola, PF Udani, TM Soparkar, PM TI A comprehensive dental survey of Kuwaiti schoolchildren. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT 1st Annual Meeting of the International-Association-for-Dental-Research CY OCT 02-04, 2001 CL KUWAIT UNIV, KUWAIT, KUWAIT SP Int Assoc Dent Res HO KUWAIT UNIV C1 Minist Hlth, Kuwait, Kuwait. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 SI B BP B330 EP B330 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 632HM UT WOS:000180217902407 ER PT J AU Ritwik, P Al Mutawa'a, S Al Duwairy, Y Udani, TM Soparkar, PM AF Ritwik, P Al Mutawa'a, S Al Duwairy, Y Udani, TM Soparkar, PM TI Study of the dental health awareness of Kuwaiti parents SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT 1st Annual Meeting of the International-Association-for-Dental-Research CY OCT 02-04, 2001 CL KUWAIT UNIV, KUWAIT, KUWAIT SP Int Assoc Dent Res HO KUWAIT UNIV C1 Minist Hlth, Kuwait, Kuwait. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 SI B BP B330 EP B330 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 632HM UT WOS:000180217902408 ER PT J AU George, MS Nahas, Z Kozel, FA Li, XB Denslow, S Yamanaka, K Mishory, A Foust, MJ Bohning, DE AF George, MS Nahas, Z Kozel, FA Li, XB Denslow, S Yamanaka, K Mishory, A Foust, MJ Bohning, DE TI Mechanisms and state of the art of transcranial magnetic stimulation SO JOURNAL OF ECT LA English DT Review DE transcranial; magnetic; stimulation; TMS; therapeutics ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; HUMAN CEREBRAL-CORTEX; LONG-TERM DEPRESSION; MAJOR DEPRESSION; MOTOR CORTEX; ELECTROCONVULSIVE-THERAPY; ELECTRICAL-STIMULATION; PARKINSONS-DISEASE; PREFRONTAL CORTEX AB In 1985, Barker et al. built a transcranial magnetic stimulation (TMS) device with enough power to stimulate dorsal roots in the spine. They quickly realized that this machine could likely also noninvasively stimulate the superficial cortex in humans. They waited a while before using their device over a human head, fearing that the TMS pulse might magnetically "erase the hard-drive" of the human brain. Almost 10 years later, in 1994, an editorial in this journal concerned whether TMS might evolve into a potential antidepressant treatment. In the intervening years, there has been an explosion of basic and clinical research with and about TMS. Studies are now uncovering the mechanisms by which TMS affects the brain. It does not "erase the hard-drive" of the brain, and it has many demonstrated research and clinical uses. This article reviews the major recent advances with this interesting noninvasive technique for stimulating the brain, critically reviewing the data on whether TMS has anticonvulsant effects or modulates cortical-limbic loops. C1 Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, 67 President St,502 N,IOP, Charleston, SC 29425 USA. RI Kozel, Frank/I-5366-2012 FU NIA NIH HHS [R01-AG40956] NR 139 TC 54 Z9 59 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD DEC PY 2002 VL 18 IS 4 BP 170 EP 181 DI 10.1097/00124509-200212000-00002 PG 12 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 626DH UT WOS:000179856700002 PM 12468991 ER PT J AU Ferris, TG Blumenthal, D Woodruff, PG Clark, S Camargo, CA AF Ferris, TG Blumenthal, D Woodruff, PG Clark, S Camargo, CA TI Insurance and quality of care for adults with acute asthma SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE asthma; acute asthma; emergency department; primary care; quality; insurance; managed care; length of stay; uninsured; Medicaid ID HEALTH MAINTENANCE ORGANIZATION; MANAGED CARE; RANDOMIZED TRIAL; MEDICAL-CARE; CHILDREN; RISK; HOSPITALIZATION; SPECIALISTS; EDUCATION; ACCESS AB OBJECTIVE: The relationship between health care insurance and quality of medical care remains incompletely studied. We sought to determine whether type of patient insurance is related to quality of care and subsequent outcomes for patients who arrive in the emergency department (ED) for acute asthma. DESIGN: Using prospectively collected data from the Multicenter Airway Research Collaboration, we compared measures of quality of pre-ED care, acute severity, and short-term outcomes across 4 insurance categories: managed care, indemnity, Medicaid, and uninsured. SETTING AND PARTICIPANTS: Emergency departments at 57 academic medical centers enrolled 1,019 adults with acute asthma. RESULTS: Patients with managed care ranked first and uninsured patients ranked last on all 7 unadjusted quality measures. After controlling for covariates, uninsured patients had significantly lower quality of care than indemnity patients for 5 of 7 measures and had lower initial peak expiratory flow rates than indemnity insured patients. Patients with managed care insurance were more likely than indemnity-insured patients to identify a primary care physician and report using inhaled steroids in the month prior to arrival in the ED. Patients with Medicaid insurance were more likely than indemnity-insured patients to use the ED as their usual source of care for problems with asthma. We found no differences in patient outcomes among the insurance categories we studied. CONCLUSIONS: Uninsured patients had consistently poorer quality of care and than insured patients. Despite differences in indicators of quality of care between types of insurance, we found no differences in short-term patient outcomes by type of insurance. C1 Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA. RP Ferris, TG (reprint author), Partners MGH Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-03533, HL-63253]; NICHD NIH HHS [HD-00850, K12 HD000850] NR 48 TC 19 Z9 19 U1 4 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2002 VL 17 IS 12 BP 905 EP 913 DI 10.1046/j.1525-1497.2002.20230.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 624ZH UT WOS:000179791800003 PM 12472926 ER PT J AU Covinsky, KE AF Covinsky, KE TI Malnutrition and bad outcomes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID PROTEIN-ENERGY UNDERNUTRITION; MEDICAL PATIENTS C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Covinsky, KE (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. NR 14 TC 8 Z9 10 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2002 VL 17 IS 12 BP 956 EP 957 DI 10.1046/j.1525-1497.2002.21011.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 624ZH UT WOS:000179791800009 PM 12472933 ER PT J AU Boulis, A Goold, S Ubel, PA AF Boulis, A Goold, S Ubel, PA TI Responding to the immunoglobulin shortage: A case study SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Article ID GLOBULIN THERAPY AB In fall 1997, a shortage of intravenous immunoglobulin (IVIG) developed in the United States because of increased demand for the product, reduced supply, and product recalls. This shortage is a useful model for understanding how our health care system responds to scarcity. Although the U.S. government took steps to inform the medical community of the shortage, with few exceptions, the government did not respond to the shortage in a timely or effective manner. Instead, it took a relatively passive role, leaving IVIG manufacturers and distributors, health care institutions, and clinicians to fend for themselves. The shortage likely had an uneven impact on patients, based on the relative market strength of the health care institutions in which they received care and the individual patient's ability to absorb the increasing out-of-pocket costs of scarce IVIG. Market mechanisms have now largely alleviated the shortage and significantly reduced its detrimental impact on patients. However, future shortages of IVIG or other scarce medical products, such as vaccines and antibiotics, would benefit from more immediate and coordinated efforts not only to make sure that scarce health care resources are distributed in a just manner but also to identify and remedy the sources of health product supply problems. C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Boulis, A (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. OI Goold, Susan Dorr/0000-0002-0258-9774 FU NCI NIH HHS [R01 CA 78052-01] NR 20 TC 20 Z9 21 U1 1 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD DEC PY 2002 VL 27 IS 6 BP 977 EP 999 DI 10.1215/03616878-27-6-977 PG 23 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA 636TW UT WOS:000180474000004 PM 12556024 ER PT J AU Hourigan, LA Walters, DL Keck, SA Dec, GW AF Hourigan, LA Walters, DL Keck, SA Dec, GW TI Heparin-induced thrombocytopenia: A common complication in cardiac transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID MANIFESTATIONS AB Background: Heparin-induced thrombocytopenia (HIT) is an idiosyncratic complication of heparin therapy triggered by the development of immunoglobulin G (IgG) antibodies to platelet factor 4 heparin. It typically results in a 50% decrease in platelet count. Paradoxically, although bleeding is rare, there is a high risk of venous or arterial thrombotic events. Given that many patients awaiting transplantation are exposed to heparin for prolonged periods, we sought to determine the frequency of HIT and its consequences among patients before and after cardiac transplantation.. Methods: We reviewed retrospectively the clinical, pathologic, and laboratory databases for all patients who underwent heart transplantation at,our institution between January 1, 1998, and December 31, 2000. An enzyme-linked immunoabsorption assay (ELISA) that detected IgG, IgA, and IgM antibodies directed against platelet factor 4 heparin complex confirmed the diagnosis of HIT. We analyzed bleeding and thrombotic complications and determined the influence of HIT on post-transplant outcomes. Results: An assay, for HIT antibody was performed before or after transplantation in 26 of 46 patients (46% of the entire cohort). In all cases, the clinical indication for testing was thrombocytopenia. Among patients screened, HIT antibody was detected-in 11 patients (39%); HIT developed in 10 of 11 patients before transplantation. The mean platelet count at diagnosis was 88,000 +/- 22,000/mm(3). Heparin-induced thrombocytopenia with thrombosis syndrome developed in 5 of 11 patients (45%). Manifestations included splenic and renal infarctions, renal artery occlusion, coronary artery embolism with myocardial infarction, pulmonary embolism, and femoral and jugular venous occlusions. Alternative pre-operative anti-coagulation included lepirudin (n = 7), argatroban (n = 1), dalteparin (n = 1), and abciximab (n = 1). Two deaths occurred in the HIT-positive group; neither bleeding nor thrombosis caused either death. Actuarial 36-month survival did not differ between HIT-positive and HIT-negative cohorts (78% and 79%, respectively). Conclusion: Heparin-induced thrombocytopenia is a frequent complication among patients hospitalized for heart failure who are awaiting-heart transplantation. Timely HIT-antibody screening and the use of alternative forms of systemic anti-coagulation may permit successful transplantation with intermediate survival rates comparable to those of HIT-negative recipients. C1 Massachusetts Gen Hosp, Heart Failure & Transplantat Unit, Boston, MA 02114 USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Heart Failure & Transplantat Unit, Boston, MA 02114 USA. RI Walters, Darren/A-7069-2011 NR 20 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 2002 VL 21 IS 12 BP 1283 EP 1289 AR PII S1053-2498(02)00458-8 DI 10.1016/S1053-2498(02)00458-8 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 627WT UT WOS:000179959800004 PM 12490273 ER PT J AU Frederickson, CJ Suh, SW Koh, JY Cha, YK Thompson, RB LaBuda, CJ Balaji, RV Cuajungco, MP AF Frederickson, CJ Suh, SW Koh, JY Cha, YK Thompson, RB LaBuda, CJ Balaji, RV Cuajungco, MP TI Depletion of intracellular zinc from neurons by use of an extracellular chelator in vivo and in vitro SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE zinc; hippocampus; nitric oxide; TSQ; (N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide); neurotoxicity; CaEDTA ID CORTICAL-NEURONS; BRAIN; TRANSPORTER; INJURY AB The membrane-impermeable chelator CaEDTA was introduced extracellularly among neurons in vivo and in vitro for the purpose of chelating extracellular Zn2+. Unexpectedly, this treatment caused histochemically reactive Zn2+ in intracellular compartments to drop rapidly. The same general result was seen with intravesicular Zn2+, which fell after CaEDTA infusion into the lateral ventricle of the brain, with perikaryal Zn2+ in Purkinje neurons (in vivo) and with cortical neurons (in vitro). These findings suggest either that the volume of zinc ion efflux and reuptake is higher than previously suspected or that EDTA can enter cells and vesicles. Caution is therefore warranted in attempting to manipulate extracellular or intracellular Zn2+ selectively. C1 NeuroBioTex Inc, Galveston, TX 77550 USA. Univ Ulsan, Coll Med, Natl Creat Res Initiat Ctr Study CNS Zinc, Seoul, South Korea. Univ Maryland, Sch Med, Dept Biochem, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Frederickson, CJ (reprint author), NeuroBioTex Inc, 101 Christopher Columbus Blvd, Galveston, TX 77550 USA. RI Cuajungco, Math/B-2647-2008; Koh, Jae-Young/C-9014-2011 OI Cuajungco, Math/0000-0003-0749-9564; Koh, Jae-Young/0000-0002-4318-495X FU NINDS NIH HHS [NS40215, NS42882] NR 13 TC 54 Z9 54 U1 0 U2 0 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 DEC PY 2002 VL 50 IS 12 BP 1659 EP 1662 PG 4 WC Cell Biology SC Cell Biology GA 634GY UT WOS:000180332700010 PM 12486088 ER PT J AU Pillai, SK Sakoulas, G Wennersten, C Eliopoulos, GM Moellering, RC Ferraro, MJ Gold, HS AF Pillai, SK Sakoulas, G Wennersten, C Eliopoulos, GM Moellering, RC Ferraro, MJ Gold, HS TI Linezolid resistance in Staphylococcus aureus: Characterization and stability of resistant phenotype SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RIBOSOMAL-RNA; MUTATIONS; SITE AB Linezolid is an important therapeutic option for treatment of infections caused by glycopeptide- and beta-lactam-resistant gram-positive organisms. Linezolid resistance is caused by mutations within the domain V region of the 23S ribosomal RNA (rRNA) gene, which is present in multiple copies in most bacteria. Among clinical Staphylococcus aureus isolates, there has been only 1 reported case of linezolid resistance. In the present study, this isolate was further characterized by determination of the number of mutant 23S rRNA copies, assessment of the stability of the resistant phenotype, and comparison of its growth characteristics with those of linezolid-susceptible S. aureus. All 5 copies of the 23S rRNA gene contained a G2576U mutation in the domain V region. After serial passage on antibiotic-free medium, the isolate maintained resistance to high concentrations of linezolid. Compared with 2 linezolid-susceptible S. aureus isolates, the linezolid-resistant S. aureus isolate demonstrated no significant differences in in vitro growth characteristics. C1 Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pillai, SK (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Harvard Inst Med Bldg,Rm 219,4 Blackfan Cir, Boston, MA 02115 USA. NR 19 TC 108 Z9 112 U1 0 U2 4 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 DEC 1 PY 2002 VL 186 IS 11 BP 1603 EP 1607 DI 10.1086/345368 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 613RH UT WOS:000179144900009 PM 12447736 ER PT J AU Lin, CB Babiarz, L Liebel, F Roydon Price, E Kizoulis, M Gendimenico, GJ Fisher, DE Seiberg, M AF Lin, CB Babiarz, L Liebel, F Roydon Price, E Kizoulis, M Gendimenico, GJ Fisher, DE Seiberg, M TI Modulation of microphthalmia-associated transcription factor gene expression alters skin pigmentation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE lipoic acid; microphthalmia; pigmentation; traditional Chinese medicine; tyrosinase; ultraviolet ID MELANOCYTE-STIMULATING HORMONE; WAARDENBURG SYNDROME TYPE-2; UNIQUE DITERPENE ACTIVATOR; KERATINOCYTE CELL-LINE; MAMMALIAN TYROSINASE; LIPOIC ACID; CYCLIC-AMP; MITF GENE; PROMOTER; SOX10 AB The microphthalmia-associated transcription factor is implicated in melanocyte development and in the regulation of melanogenesis. Microphthalmia-associated transcription factor is thought to bind to the M-box promoter elements of tyrosinase, tyrosinase-related protein-1 and dopachrome tautomerase/tyrosinase-related protein-2 and transactivate these genes, resulting in increased pigmentation. Using a luciferase reporter construct driven by the microphthalmia-associated transcription factor promoter, we identified agents that modulate microphthalmia-associated transcription factor promoter activity. Changes in endogenous microphthalmia-associated transcription factor expression levels upon treatment with these agents were confirmed using northern and western blots, and their pigmentary modulating activities were demonstrated. Ultraviolet B irradiation and traditional Chinese medicine-1, a natural extract used in traditional Chinese medicine, upregulated microphthalmia-associated transcription factor gene expression and enhanced tyrosinase activity in vitro . Dihydrolipoic acid, lipoic acid, and resveratrol reduced microphthalmia-associated transcription factor and tyrosinase promoter activities. These agents also inhibited the forskolin- and ultraviolet B-stimulated promoter activities of these genes and significantly reduced tyrosinase activity in melanocyte cultures, resulting in depigmentation. Overexpressed microphthalmia-associated transcription factor was capable of rescuing the repressive effects of these compounds on the cotransfected tyrosinase promoter. Dark-skinned Yucatan swine treated with these agents showed visible skin lightening, which was confirmed histologically, whereas ultraviolet B-induced tanning of light-skinned swine was inhibited using these agents. Our findings suggest that modulation of microphthalmia-associated transcription factor expression can alter skin pigmentation and further confirm the central role of microphthalmia-associated transcription factor in melanogenesis. C1 Johnson & Johnson, Skin Res Ctr, Consumer & Personal Care Grp, CPWW, Skillman, NJ 08588 USA. Dana Farber Canc Res Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Seiberg, M (reprint author), Johnson & Johnson, Skin Res Ctr, Consumer & Personal Care Grp, CPWW, 199 Grandview Rd, Skillman, NJ 08588 USA. NR 76 TC 48 Z9 51 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2002 VL 119 IS 6 BP 1330 EP 1340 DI 10.1046/j.1523-1747.2002.19615.x PG 11 WC Dermatology SC Dermatology GA 625ED UT WOS:000179803200018 PM 12485436 ER PT J AU Werth, VP Berlin, JA Callen, JP Mick, R Sullivan, KE AF Werth, VP Berlin, JA Callen, JP Mick, R Sullivan, KE TI Mannose binding lectin (MBL) polymorphisms associated with low MBL production in patients with dermatomyositis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT Annual Scientific Sessions of the Society-for-Investigative-Dermatology CY 2002 CL LOS ANGELES, CALIFORNIA SP Soc Investigat Dermatol DE TNF alpha; apoptosis; lupus; autoimmunity; photosensitivity ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR-ALPHA; CUTANEOUS LUPUS; PROTEIN GENE; RHEUMATOID-ARTHRITIS; KERATINOCYTE APOPTOSIS; COMPLEMENT DEFICIENCY; C1Q; TOXOPLASMOSIS; CELLS AB One theory for the pathophysiology of photosensitive autoimmune skin diseases is that photoinduction of tumor necrosis factor alpha (TNFalpha) secretion leads to keratinocyte apoptosis and translocation of previously sequestered cellular antigens that then activate the immune system. We previously found an association of the overproducing TNFalpha-308 A variant with adult dermatomyositis and with subacute cutaneous lupus erythematosus. Here we focused on mannose binding lectin (MBL), which is one of several proteins involved in clearance of apoptotic cells and could thereby lessen photosensitive autoimmunity. We examined three variant MBL polymorphisms associated with decreased MBL protein (Asp(54) , Glu(57) , and the LX promoter polymorphism) in adult dermatomyositis, subacute cutaneous lupus erythematosus, and discoid lupus, and controls. The variant Asp(54) allele was positively associated with adult dermatomyositis in a dose-responsive fashion (p=0.0004), as was the Glu(57) allele (p=0.004). None of the three variant MBL alleles considered individually was significantly associated with either subacute cutaneous lupus erythematosus or discoid lupus. In adult dermatomyositis patients homozygous for the wild-type TNFalpha-308G allele (GG), i.e., presumably without elevated TNFalpha production, 69% had at least two of the MBL polymorphisms, versus 20% of healthy GG controls (p=0.0011). Combinations of low-producing MBL variants were over-represented in adult dermatomyositis in a dose-responsive fashion (p=0.0002). In adult dermatomyositis patients with one variant TNFalpha-308 A allele (GA), 46% had at least two MBL polymorphisms, versus 7% of GA controls (p=0.0077). Thus, low-producing MBL genes are very strongly associated with adult dermatomyositis. Our model is that genetic polymorphisms leading to overproduction of apoptotic keratinocytes and then impaired clearance of these cells contribute to the pathogenesis of adult dermatomyositis, a photoinduced autoimmune skin disease. C1 Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Louisville, Dept Dermatol, Louisville, KY 40292 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Univ Penn, Dept Dermatol, 2 Rhoads Pavil,36th & Spruce Sts, Philadelphia, PA 19104 USA. OI Sullivan, Kathleen/0000-0003-4018-1646 FU NIAMS NIH HHS [1K24AR002207-01] NR 58 TC 30 Z9 31 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2002 VL 119 IS 6 BP 1394 EP 1399 DI 10.1046/j.1523-1747.2002.19608.x PG 6 WC Dermatology SC Dermatology GA 625ED UT WOS:000179803200027 PM 12485445 ER PT J AU Antezana, MA Sullivan, SR Usui, ML Gibran, NS Spenny, ML Larsen, JA Ansel, JC Bunnett, NW Olerud, JE AF Antezana, MA Sullivan, SR Usui, ML Gibran, NS Spenny, ML Larsen, JA Ansel, JC Bunnett, NW Olerud, JE TI Neutral endopeptidase activity is increased in the skin of subjects with diabetic ulcers SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE inflammation; nerves; neuropeptides; substanceP; wound healing ID SUBSTANCE-P; NERVE-FIBERS; ENDOTHELIAL-CELLS; NEUROPEPTIDES; INFLAMMATION; EXPRESSION; MELLITUS; GROWTH; PROLIFERATION; NEUTROPHILS AB Cutaneous sensory nerves mediate inflammation and wound healing by releasing neuropeptides, such as substance P , which stimulates pro-inflammatory responses by keratinocytes, fibroblasts, and endothelial cells. The cell surface enzyme, neutral endopeptidase, degrades substance P , thereby regulating its biologic actions. We hypothesized that neutral endopeptidase enzymatic activity is increased in chronic wounds and skin from subjects with diabetes. We compared cutaneous neutral endopeptidase expression and enzymatic activity between normal controls and diabetic subjects with neuropathy and chronic wounds. Skin samples from subjects with diabetes were taken at the time of amputation for nonhealing ulcers. Skin taken from the ulcer margin, 1 cm from the ulcer (adjacent), and from the most proximal region of the amputated leg were studied. Skin biopsies from the leg of healthy control subjects were also studied. Neutral endopeptidase was localized by immunohistochemistry in all tissue sections. Neutral endopeptidase activity was measured using a fluorimetric assay. The median neutral endopeptidase activity of the ulcer margin was 1.21 x higher (p>0.2) than adjacent skin, 5.26 x higher (p<0.001) than proximal skin, and 15.22 x higher (p<0.001) than control skin. Adjacent skin had a median neutral endopeptidase activity 4.34 x higher (p<0.001) than proximal skin and 12.58 x higher (p<0.001) than control skin. The median neutral endopeptidase activity of proximal skin was 2.90 x higher (p<0.001) than control skin. This elevated neutral endopeptidase activity in the skin and chronic ulcers of subjects with diabetes combined with peripheral neuropathy may contribute to deficient neuroinflammatory signaling and may impair wound healing in subjects with diabetes. C1 Univ Washington, Dept Med Dermatol, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Orthopaed, Seattle, WA USA. Emory Univ, Dept Dermatol, Atlanta, GA 30322 USA. UCSF, Dept Physiol, San Francisco, CA USA. UCSF, Dept Surg, San Francisco, CA USA. RP Olerud, JE (reprint author), Univ Washington, Dept Med Dermatol, 1959 NE Pacific St,Box 356524, Seattle, WA 98195 USA. RI Sullivan, Stephen/C-6389-2013 NR 38 TC 35 Z9 36 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2002 VL 119 IS 6 BP 1400 EP 1404 DI 10.1046/j.1523-1747.2002.19618.x PG 5 WC Dermatology SC Dermatology GA 625ED UT WOS:000179803200028 PM 12485446 ER PT J AU Small, GW Agdeppa, ED Kepe, V Satyamurthy, N Huang, SC Barrio, JR AF Small, GW Agdeppa, ED Kepe, V Satyamurthy, N Huang, SC Barrio, JR TI In vivo brain imaging of tangle burden in humans SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Alzheimer's disease; positron emission tomography; cerebral glucose metabolism; neurofibrillary tangles ID POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; DIAGNOSIS; PLAQUES; ALLELE; RISK; PET AB Cerebral neurofibrillary tangles (NFTs) accumulate in a predictable sequence decades before the clinical symptoms of Alzheimer's disease emerge, and the degree of tangle degeneration correlates with the severity of cognitive impairment. A valid in vivo marker of tangle burden, therefore, would be useful for presymptomatic and symptomatic disease detection and treatment monitoring. Recent advances using positron emission tomography (PET) indicate the feasibility of in vivo imaging that provides a combined signal of both neurofibrillary tangles and senile plaques. Such results are encouraging that a tangle-specific marker will be found; however, several methodological issues first need to be addressed, including scanner spatial resolution in the relatively small brain regions where tangles accumulate. NFT-specific imaging probes will need to be lipophilic in order to cross the blood-brain barrier and neuronal membranes and have a high binding affinity to NFTs with minimal nonspecific binding, which would result in a high signal-to-background ratio in PET images. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Alzheimers Dis Res Ctr, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Aging, Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Small, GW (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Sch Med, 760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIA NIH HHS [AG10123, AG13308]; NIMH NIH HHS [MH52453] NR 27 TC 32 Z9 34 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 2002 VL 19 IS 3 BP 323 EP 327 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 633BT UT WOS:000180259900011 PM 12540059 ER PT J AU Wang, XX Qin, ZH Leng, Y Wang, YM Jin, XN Chase, TN Bennett, MC AF Wang, XX Qin, ZH Leng, Y Wang, YM Jin, XN Chase, TN Bennett, MC TI Prostaglandin A(1) inhibits rotenone-induced apoptosis in SH-SY5Y cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE caspase-3; dopaminergic cell; mitochondrial complex I; nuclear factor-kappa B; Parkinson's disease; prostaglandin A1 ID NF-KAPPA-B; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; CYCLOPENTENONE PROSTAGLANDINS; ACTIVATION; HSP27; HSP70; PHOSPHORYLATION; MITOCHONDRIA; EFFECTOR AB The degeneration of nigral dopamine neurons in Parkinson's disease (PD) reportedly involves a defect in brain mitochondrial complex I in association with the activation of nuclear factor-kappaB (NF-kappaB) and caspase-3. To elucidate molecular mechanisms possibly linking these events, as well as to evaluate the neuroprotective potential of the cyclopentenone prostaglandin A(1) (PGA(1)), an inducer of heat shock proteins (HSPs), we exposed human dopaminergic SH-SY5Y cells to the complex I inhibitor rotenone. Dose-dependent apoptosis was preceded by the nuclear translocation of NF-kappaB and then the activation of caspase-3 over the ensuing 24 h. PGA(1) increased the expression of HSP70 and HSP27 and protected against rotenone-induced apoptosis, without increasing necrotic death. PGA(1) blocked the rotenone-induced nuclear translocation of NF-kappaB and attenuated, but did not abolish, the caspase-3 elevation. Unexpectedly, the caspase-3 inhibitor, Ac-DEVD.CHO (DEVD), at a concentration that completely prevented the caspase-3 elevation produced by rotenone, failed to protect against apoptosis. These results suggest that complex I deficiency in dopamine cells can induce apoptosis by a process involving early NF-kappaB nuclear translocation and caspase-3 activation. PGA, appears to protect against rotenone-induced cell death by inducing HSPs and blocking nuclear translocation of NF-kappaB in a process that attenuates caspase-3 activation, but is not mediated by its inhibition. C1 NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Lab Cellular & Neurobiol, Boston, MA USA. Walter Reed Army Inst Res, Dept Biol, Div Expt Therapeut, Silver Spring, MD USA. Blanchette Rockefeller Neurosci Inst, Rockville, MD USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, Bldg 10,Room 5C-103,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA. NR 48 TC 59 Z9 64 U1 1 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2002 VL 83 IS 5 BP 1094 EP 1102 DI 10.1046/j.1471-4159.2002.01224.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 621CR UT WOS:000179571400008 PM 12437580 ER PT J AU Kinney, GA Spain, WJ AF Kinney, GA Spain, WJ TI Synaptically evoked GABA transporter currents in neocortical glia SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; PLASMA-MEMBRANE TRANSPORTER; NA+CL COTRANSPORT FUNCTION; CEREBELLAR GRANULE CELLS; HIPPOCAMPAL CA1 NEURONS; RAT CEREBRAL-CORTEX; GLUTAMATE TRANSPORTERS; HORIZONTAL CELLS; PHARMACOLOGICAL CHARACTERIZATION; EXTRASYNAPTIC GLUTAMATE AB The presence, magnitude, and time course of GABA transporter currents were investigated in electrophysiologically characterized neocortical astrocytes in an in vitro slice preparation. On stimulation with a bipolar-tungsten stimulating electrode placed nearby, the majority of cells tested displayed long-lasting GABA transporter currents using both single and repetitive stimulation protocols. Using subtype-specific GABA transporter antagonists, long-lasting GABA transporter cur-rents were identified in neocortical astrocytes that originated from at least two subtypes of GABA transporters: GAT-1 and GAT-2/3. These transporter currents displayed slow rise times and long decay times, contrasting the time course observed for glutamate transporter currents, and are indicative of a long extracellular time course of GABA as well as a role for glial GABA transporters during synaptic transmission. C1 Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Sch Med, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Neurol, Sch Med, Seattle, WA 98104 USA. Univ Washington, Dept Physiol & Biophys, Sch Med, Seattle, WA 98104 USA. RP Kinney, GA (reprint author), Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Sch Med, Box 359740,325 9th Ave, Seattle, WA 98104 USA. FU BLRD VA [I01 BX000386]; NINDS NIH HHS [NS-07395] NR 82 TC 32 Z9 34 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2002 VL 88 IS 6 BP 2899 EP 2908 DI 10.1152/jn.00037.2002 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 626HK UT WOS:000179865600002 PM 12466416 ER PT J AU Rinn, W Desai, N Rosenblatt, H Gastfriend, DR AF Rinn, W Desai, N Rosenblatt, H Gastfriend, DR TI Addiction denial and cognitive dysfunction: A preliminary investigation SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID UNAWARENESS; ANOSOGNOSIA; HEMIPLEGIA; DISEASE AB This study explored the proposition that denial of addiction is often more a product of cognitive failure dice to cerebral dysfunction than an emotion-driven rejection of the truth. Forty-four subjects were studied in an inpatient alcohol rehabilitation program. Denial was defined as the proportion of standardized denial-related treatment goals established at admission that remained unachieved at discharge. Cognitive deficiencies were identified through neuropsychological assessments. Persistent denial was significantly correlated with greater impairment of executive function, verbal memory , visual inference, and mental speed. C1 Spaulding Rehabil Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Rinn, W (reprint author), Spaulding Rehabil Hosp, 125 Nashua St, Boston, MA 02114 USA. FU NIDA NIH HHS [K24-DA00427, R01-DA08781] NR 24 TC 41 Z9 41 U1 1 U2 10 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 2002 VL 14 IS 1 BP 52 EP 57 DI 10.1176/appi.neuropsych.14.1.52 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 517BD UT WOS:000173590500009 PM 11884655 ER PT J AU Taylor, AN Romeo, HE Beylin, AV Tio, DL Rahman, SU Hovda, DA AF Taylor, AN Romeo, HE Beylin, AV Tio, DL Rahman, SU Hovda, DA TI Alcohol consumption in traumatic brain injury: Attenuation of TBI-induced hyperthermia and neurocognitive deficits SO JOURNAL OF NEUROTRAUMA LA English DT Article DE alcohol; brain temperature; core body temperature; hyperthermia; neuroprotection; spatial learning; traumatic brain injury ID ACUTE-PHASE RESPONSE; HEAD-INJURY; MODERATE HYPOTHERMIA; CORTICAL CONTUSION; ETHANOL; RATS; INTERLEUKIN-6; TEMPERATURE; INTOXICATION; PROTECTION AB Clinical and animal studies indicate that hyperthermia during or after traumatic brain injury (TBI) is associated with poor outcome. Alcohol intoxication, a complicating risk factor in many cases of head injury, has been found to both worsen or attenuate posttraumatic neural damage and outcome. The purpose of the present study was to determine whether chronic ethanol consumption would affect TBI-induced hyperthermia and deficits in spatial learning. TBI was produced by cortical contusion injury in adult male rats. We first characterized the TBI-induced febrile response using probes implanted intraperitoneally (ip) or intracerebroventricularly for continuous biotelemetric recording of core body and brain temperatures and locomotor activity. In another experiment, rats, implanted with ip probes, were fed a liquid diet containing ethanol (5% w/v, 35% ethano/derived calories); control rats were pair-fed the isocaloric liquid diet (P-P). At 14 days after commencement of diet feeding, TBI or sham surgery was performed, and the ethanol-fed rats were divided into two groups: half were transferred to the isocaloric diet (E-P) and the other half remained on the ethanol-containing diet (E-E). TBI produced a significant febrile response in all rats, that persisted for at least 6 days in the E-P and P-P groups but lasted for only 2 days in the E-E group. When tested at 3-4 weeks after TBI, E-E rats required significantly fewer trials than E-P rats to reach criterion in the Morris water maze. In sum, continuous consumption of ethanol before and after TBI attenuated TBI-induced hyperthermia and deficits in spatial learning. Whereas the results suggest that this ethanol regimen may be neuroprotective, a causal relationship between the two outcomes remains to be determined. C1 Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Taylor, AN (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurobiol, 10833 Le Conte Ave,Box 951763, Los Angeles, CA 90095 USA. FU NIAAA NIH HHS [AA09850] NR 50 TC 26 Z9 27 U1 1 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD DEC PY 2002 VL 19 IS 12 BP 1597 EP 1608 DI 10.1089/089771502762300256 PG 12 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 629UY UT WOS:000180070700007 PM 12542860 ER PT J AU Langleben, DD Acton, PD Austin, G Elman, I Krikorian, G Monterosso, JR Portnoy, O Ridlehuber, HW Strauss, HW AF Langleben, DD Acton, PD Austin, G Elman, I Krikorian, G Monterosso, JR Portnoy, O Ridlehuber, HW Strauss, HW TI Effects of methylphenidate discontinuation on cerebral blood flow in prepubescent boys with attention deficit hyperactivity disorder SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE methylphenidate; statistical parametric mapping; SPECT; attention deficit hyperactivity disorder; motor cortex; anterior cingulate cortex ID ANTERIOR CINGULATE CORTEX; DEFICIT/HYPERACTIVITY DISORDER; MOTOR CORTEX; CHILDREN; AMPHETAMINE; ADHD; DYSFUNCTION; METABOLISM; INHIBITION; BEHAVIOR AB Methylphenidate (MPH) is an effective symptomatic treatment of attention deficit hyperactivity disorder (ADHD), but the mechanisms of its therapeutic action have not been fully elucidated. To address this issue, we assessed the effects of discontinuation of chronic MPH treatment on regional cerebral blood flow (rCBF) in ADHD patients. Methods: Twenty-two prepubescent boys with ADHD (age range, 8.2-11.5 y) and 7 healthy volunteers were studied with SPECT on and off MPH. Their rCBF data were automatically normalized to whole-brain counts and coregistered with standard anatomic space. rCBF changes were evaluated with statistical parametric mapping based on voxel-by-voxel ANOVA. Results: When the subjects were not taking MPH, rCBF was higher in the motor, premotor, and the anterior cingulate cortices (Brodmann's areas 4, 6, and 32). Conclusion: Brief discontinuation of MPH treatment is associated with increased motor and anterior cingulate cortical activity. Our findings suggest that MPH treatment modulates motor and anterior cingulate cortical activity directly or indirectly. Alternatively, our findings may be related to MPH withdrawal. These data provide novel information on the potential mechanisms of the therapeutic action of MPH. Furthermore, they are clinically relevant to the commonly occurring brief interruptions in MPH treatment. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Radiol, Philadelphia, PA 19104 USA. Community Acad Coalit, Mt View, CA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Stanford Univ, Sch Med, Div Nucl Med, Palo Alto, CA 94304 USA. RP Langleben, DD (reprint author), Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. RI Langleben, Daniel/K-7407-2014 NR 41 TC 37 Z9 38 U1 1 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2002 VL 43 IS 12 BP 1624 EP 1629 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 622WG UT WOS:000179670100013 PM 12468511 ER PT J AU Mukherjee, S Rodrigues, E Weker, R Palmer, LJ Christiani, DC AF Mukherjee, S Rodrigues, E Weker, R Palmer, LJ Christiani, DC TI 1-hydroxypyrene as a biomarker of occupational exposure to polycyclic aromatic hydrocarbons (PAH) in boilermakers SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID AIR-POLLUTION AB A repeated measures short-term prospective study was Performed in boilermakers to determine occupational polycyclic aromatic hydrocarbon (PAH) exposure using the biomarker, 1-hydroxypyrene (1-OHP). Two work sites were studied; an apprentice school (metal fume exposure) and a boiler overhaul (residual oil fly ash [ROFA] and metal fume exposure). Pre- and postshift urine samples (n = 24 1; 41 male subjects) were analyzed for cotinine and 1-OHP. Descriptive statistics and generalized estimating equations were calculated. At the apprentice school cross-shift 1-OHP levels did not significantly differ. At the overhaul 1-OHP levels increased during the week in smokers and nonsmokers; in nonsmokers the 1-OHP level increased significantly postshifit compared to Preshift. In conclusion this study suggests that boilermakers exposed to occupational particulates are exposed to PAH. The urinary 1-OHP level may be a useful biomarker of PAH exposure in boilermakers exposed to ROFA, particularly in nonsmokers. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Environm Sci & Engn Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Palmer, Lyle/K-3196-2014 OI Palmer, Lyle/0000-0002-1628-3055 FU NIEHS NIH HHS [ES00002, ES09860] NR 35 TC 14 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD DEC PY 2002 VL 44 IS 12 BP 1119 EP 1125 DI 10.1097/01.jom.0000044125.59147.51 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 624UU UT WOS:000179780700004 PM 12500453 ER PT J AU Nathan, DG AF Nathan, DG TI Search for improved therapy of sickle cell anemia SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Editorial Material ID FETAL HEMOGLOBIN PRODUCTION; GAMMA-GLOBIN SYNTHESIS; BETA-THALASSEMIA; DIABETIC MOTHERS; SODIUM-BUTYRATE; DISEASE; GENE; 5-AZACYTIDINE; HYDROXYUREA; ERYTHROCYTES C1 Dana Farber Canc Inst, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, Div Hematol & Oncol, Boston, MA 02115 USA. FU NCRR NIH HHS [5M01 RR 02172]; NHLBI NIH HHS [P50 HL 54785, HL 99016] NR 33 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD DEC PY 2002 VL 24 IS 9 BP 700 EP 703 DI 10.1097/00043426-200212000-00002 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 624NA UT WOS:000179764700002 PM 12468906 ER PT J AU Loh, ML Ahn, P Perez-Atayde, AR Gebhardt, MC Shamberger, RC Grier, HE AF Loh, ML Ahn, P Perez-Atayde, AR Gebhardt, MC Shamberger, RC Grier, HE TI Treatment of infantile fibrosarcoma with chemotherapy and surgery: Results from the Dana-Farber Cancer Institute and Children's Hospital, Boston SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE infantile fibrosarcoma; chemotherapy; TEL/TRKC ID ETV6-NTRK3 GENE FUSION; CONGENITAL MESOBLASTIC NEPHROMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMORS AB Purpose: To retrospectively evaluate the treatment and outcome of patients diagnosed with infantile fibrosarcoma at the Dana-Farber Cancer Institute and Children's Hospital, Boston. Patients and Methods: Between 1982 and 1998, a total of 11 infants were diagnosed pathologically with infantile fibrosarcoma. A retrospective chart review was conducted to determine the extent of surgical therapy and chemotherapy required for a favorable clinical outcome. Cytogenetic findings were reviewed and archived tumor specimens were analyzed, when available, for the presence of the TEL/TRKC fusion gene. Results: Three patients had primary surgical resection with negative pathologic margins and have been lost to follow-up. Two patients received chemotherapy only after limited biopsy or subtotal resection and are alive with no evidence of disease 8 and 18 years from diagnosis. Four patients had limited biopsies followed by chemotherapy with delayed resection. One of these four patients had negative margins and received no further chemotherapy. The other three of these patients had positive microscopic margins; two of them received postoperative chemotherapy while the third did not. All four are currently alive with no evidence of disease. Two patients had progressive disease within 7 and 10 months of diagnosis while on chemotherapy after subtotal resections. One of these two patients is dead of disease; the other is alive after palliative radiotherapy. Seven patients had archived or frozen tissue available for molecular analysis. All seven had evidence of TEL gene rearrangement; six exhibited the TEL/TRKC fusion. Six patients had characteristic trisomies previously reported to be associated with infantile fibrosarcoma. Conclusions: Previously reported series of treatment outcomes in infantile fibrosarcoma have been limited to very few patients due to the rare occurrence of this tumor. In our experience, initial chemotherapy combined with surgery has been successful for most cases. When disease progression occurred, it was within one year of diagnosis. There was no development of distant metastases in the patients with progressive disease. The role of additional chemotherapy for microscopic margins after local control is not clear. We found a high incidence of the TEL/TRKC fusion gene, confirming its utility in diagnosis. We propose a uniform approach to treatment to gather clinical and biologic information about this rare and curable disease. C1 Univ Calif San Francisco, Dept Pediat Hematol Oncol, San Francisco, CA 94143 USA. Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Loh, ML (reprint author), Univ Calif San Francisco, Dept Pediat Hematol Oncol, San Francisco, CA 94143 USA. FU NCI NIH HHS [K23 CA 80915]; NICHD NIH HHS [HD 28825] NR 21 TC 48 Z9 51 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD DEC PY 2002 VL 24 IS 9 BP 722 EP 726 DI 10.1097/00043426-200212000-00008 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 624NA UT WOS:000179764700008 PM 12468912 ER PT J AU Fuchs, JR Terada, S Hannouche, D Ochoa, ER Vacanti, JP Fauza, DO AF Fuchs, JR Terada, S Hannouche, D Ochoa, ER Vacanti, JP Fauza, DO TI Engineered fetal cartilage: Structural and functional analysis in vitro SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Pacific-Association-of-Pediatric-Surgeons CY MAY 12-16, 2002 CL LA JOLLA, CALIFORNIA SP Pacific Assoc Pediatric Surg DE tissue engineering; cartilage engineering; cartilage; fetal surgery; congenital anomalies; transplantation ID AURICULAR CHONDROCYTES; COLLAGEN TYPES; ALGINATE; ELASTIN AB Background/Purpose: This study was aimed at characterizing the structure and function of engineered fetal cartilage in vitro. Methods: Chondrocytes from ovine specimens of fetal elastic, fetal hyaline, and adult elastic cartilage were expanded in culture and their growth rates determined. Cells were seeded onto synthetic scaffolds, which were then maintained in a bioreactor. Matrix deposition was determined by specific staining and quantitative assays for glycosaminoglycans (GAG), type II collagen (CII), and elastin, as well as compared with native tissue. Statistical analysis was by analysis of variance (ANOVA) and Students' t test, with significance set at P less than .01. Results: Fetal elastic chondrocytes grew significantly faster than all other cell types. All fetal constructs resembled hyaline cartilage, regardless of the cell source. There were significantly higher levels of GAG and CII in fetal versus adult constructs, but no significant difference between fetal constructs from different sources. Unlike their adult counterparts, fetal constructs had GAG and CII levels similar to native tissues. Conclusions: Fetal chondrocytes can be rapidly expanded in culture. Compared with adult constructs, matrix deposition is enhanced in engineered fetal cartilage, which closely resembles native tissue, regardless of the cell source. Engineered fetal cartilage may be a preferable option during surgical reconstruction of select congenital anomalies. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Minimally Invas Surg, Ctr Integrat Med & Innovat Technol, Boston, MA USA. RP Fauza, DO (reprint author), Childrens Hosp, Fegan 3,300 Longwood Ave, Boston, MA 02115 USA. NR 20 TC 22 Z9 22 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD DEC PY 2002 VL 37 IS 12 BP 1720 EP 1725 DI 10.1053/jpsu.2002.36705 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 622RQ UT WOS:000179661100019 PM 12483640 ER PT J AU Stoler, JM Ryan, LM Holmes, LB AF Stoler, JM Ryan, LM Holmes, LB TI Alcohol dehydrogenase 2 genotypes, maternal alcohol use, and infant outcome SO JOURNAL OF PEDIATRICS LA English DT Article ID POLYMORPHISM; PREGNANCY; EXPOSURE; DRINKING; RISK; ADH AB Objective: To determine whether different alleles of the ADH2 gene (ADH2-1, ADH2-2 and ADH2-3) with differing levels of enzymatic activity can alter the risk of fetal alcohol effects. Study design: ADH2 genotypes were performed on 404 pregnant high-risk women and 139 infants as part of a larger study of alcohol use in pregnancy. Mothers were interviewed about alcohol use during pregnancy, and their infants were examined for alcohol-related features without knowledge of the exposure status. Results: The ADH2-1/3 genotype was more prevalent among black women (46%) than expected (33%); the rate among white women was low as expected (2%). More black women who reported high alcohol use during the pregnancy had the ADH2-1/3 genotype compared with those who reported no alcohol use (70% vs 44%). Sixty percent of the affected black infants had the ADH2-1/3 genotype compared with 29% of the unaffected infants (P < .045). The maternal genotype correlated with her chance of having an infant with alcohol-related physical features (odds ratio = 2.49). This association remained significant after accounting for confounders, such as smoking and maternal weight gain. Alcohol exposure was not significantly associated with infant outcome in black infants after accounting for genotype, smoking, and maternal weight gain, but this association could only be tested in 10 infants of mothers with high exposure. Conclusion: Women with the ADH2-1/3 genotype may be at greater risk for having an affected infant, which may be the result of greater ingestion of alcohol. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Stoler, JM (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, 55 Fruit St, Boston, MA 02114 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 32 TC 37 Z9 37 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2002 VL 141 IS 6 BP 780 EP 785 DI 10.1067/mpd.2002.128112 PG 6 WC Pediatrics SC Pediatrics GA 625UN UT WOS:000179834100010 PM 12461493 ER PT J AU Bolchoz, LJC Gelasco, AK Jollow, DJ McMillan, DC AF Bolchoz, LJC Gelasco, AK Jollow, DJ McMillan, DC TI Primaquine-induced hemolytic anemia: Formation of free radicals in rat erythrocytes exposed to 6-methoxy-8-hydroxylaminoquinoline SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LIPID-PEROXIDATION; IRON RELEASE; ACTIVATED METMYOGLOBIN; DAPSONE HYDROXYLAMINE; ANILINE METABOLITES; HYDROGEN-PEROXIDE; RED-CELLS; SUPEROXIDE; HEMOGLOBIN; PHENYLHYDROXYLAMINE AB Primaquine is an important antimalarial drug that is often dose-limited in therapy by the onset of hemolytic anemia. We have shown recently that an N-hydroxy metabolite of primaquine, 6-methoxy-8-hydroxylaminoquinoline (MAQ-NOH), is a direct-acting hemolytic agent in rat red cells and that the hemolytic activity of this metabolite is associated with GSH oxidation and oxidative damage to both membrane lipids and skeletal proteins. To determine whether the formation of free radicals may be involved in this process, rat red cells (40% suspensions) were incubated with hemolytic concentrations of MAQ-NOH (150-750 muM) and examined by EPR spectroscopy using 2-ethoxycarbonyl-2-methyl-3,4-dihydro-2H-pyrrole-1-oxide (EMPO) as a spin trap. Addition of MAQ-NOH to red cell suspensions containing 10 mM EMPO gave rise to an EPR spectrum with hyperfine constants consistent with those of an EMPO-hydroxyl radical adduct standard. Of interest, formation of EMPO-OH was constant for up to 20 min and dependent on the presence of erythrocytic GSH. Although no other radical adduct signals were detected in the cells by EPR, spectrophotometric analysis revealed the presence of ferrylhemoglobin, which indicates that hydrogen peroxide is generated under these experimental conditions. The data support the hypothesis that oxygen-derived and possibly other free radicals are involved in the mechanism underlying MAQ-NOH-induced hemolytic anemia. C1 Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Div Nephrol, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Dept Vet Affairs, Res Serv, Charleston, SC USA. RP McMillan, DC (reprint author), Med Univ S Carolina, Dept Pharmacol, 171 Ashley Ave, Charleston, SC 29425 USA. FU NIAID NIH HHS [AI46424]; NIDDK NIH HHS [DK59950] NR 39 TC 18 Z9 20 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2002 VL 303 IS 3 BP 1121 EP 1129 DI 10.1124/jpet.102.041459 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 616EN UT WOS:000179290500030 PM 12438535 ER PT J AU Smith, SR Reddy, LA Wingenfeld, SA AF Smith, SR Reddy, LA Wingenfeld, SA TI Assessment of psychotic disorders in inpatient children and adolescents: Use of the Devereux Scales of Mental Disorders SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE psychosis; assessment of children; Devereux Scales; Behavior Rating Scales AB The Devereux Scales of Mental Disorders (DSMD), with its 3-factor model of measurement (i.e., Internalizing, Externalizing, and Critical Pathology), may be useful in screening for psychotic disorders in children. This study assessed the ability of the DSMD to differentiate between inpatient children and adolescents with psychotic disorders (n = 18) and those with other clinical syndromes (n = 71). Results of ANCOVAs indicated that the psychotic group scored significantly higher on most DSMD scales and composites than the nonpsychotic clinical group. However estimates of effect size were particularly large for the Critical Pathology Composite and the Autism and Acute Problems Scales. Diagnostic efficiency statistics revealed that the DSMD's Critical Pathology Composite was highly accurate in differentiating between the 2 clinical groups. These findings support the utility of the DSMD in identifying children and adolescents with psychotic disorders. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Fairleigh Dickinson Univ, Dept Psychol, Teaneck, NJ USA. La Trobe Univ, Sch Psychol Sci, Bundoora, Vic 3083, Australia. Austin & Repatriat Med Ctr, Heidelberg, Vic, Australia. RP Smith, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,WRN 605, Boston, MA 02114 USA. NR 21 TC 10 Z9 10 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD DEC PY 2002 VL 24 IS 4 BP 269 EP 273 DI 10.1023/A:1020731117022 PG 5 WC Psychology, Clinical SC Psychology GA 606YQ UT WOS:000178764000007 ER PT J AU Kressin, NR Spiro, A Atchison, KA Kazis, L Jones, JA AF Kressin, NR Spiro, A Atchison, KA Kazis, L Jones, JA TI Is depressive symptomatology associated with worse oral functioning and well-being among older adults? SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE oral health; quality of life; depression ID QUALITY-OF-LIFE; SEX-DIFFERENCES; HEALTH; SYMPTOMS; PATIENT; POPULATIONS; OUTCOMES; RATINGS; DISEASE; AGE AB Objectives: Although depression negatively affects individuals' physical functioning and well-being, its association with oral functioning and well-being has not been examined previously. The objective of this study was to examine the association between depressive symptomatology and oral quality of life. Methods: We utilized data from two samples of older adults: community-dwelling participants who used community primary care physicians in Los Angeles (n=1,653) and individuals who sought ambulatory care through four Department of Veterans Affairs facilities in the Boston metropolitan area (n=212). Depressive symptomatology was measured with the CES-D scale; Oral Quality of Life was measured with the Geriatric Oral Health Assessment Instrument and the Oral Health-related Quality of Life measure. We conducted hierarchical regression analyses to examine the effects of depression on oral quality of life, controlling for self-reported oral health, age, education, income, and marital status. Results: Individuals with more depressive symptoms reported worse oral quality of life, controlling for sociodemographic factors and self-reported oral health. This finding persisted across multiple samples and both sexes, and using two measures of oral quality of life. Conclusion: These findings further emphasize the importance of treating depression among older adults, and suggest that both dentists and physicians have a role in recognizing and referring patients for such treatment. C1 VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. Boston Univ, Goldman Sch Dent Med, Boston, MA 02215 USA. RP Kressin, NR (reprint author), VAMC, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70 152, Bedford, MA 01730 USA. FU NIDCR NIH HHS [R15 DE11455, R03 DE11035] NR 41 TC 26 Z9 26 U1 2 U2 3 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 2002 VL 62 IS 1 BP 5 EP 12 DI 10.1111/j.1752-7325.2002.tb03414.x PG 8 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 617JW UT WOS:000179359400002 PM 14700083 ER PT J AU Costenbader, KH Karlson, EW Liang, MH Mandl, LA AF Costenbader, KH Karlson, EW Liang, MH Mandl, LA TI Defining lupus cases for clinical studies: The Boston Weighted Criteria for the classification of systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE lupus weighted criteria; clinical studies ID REVISED CRITERIA; DISEASE; IDENTIFICATION; ASSOCIATION; PREVALENCE; ANTIBODIES; DIAGNOSIS AB Objective. The 1982 American College of Rheumatology (ACR) revised criteria for the classification of systemic lupus erythematosus (SLE), updated in 1997, have become the standard for establishing eligibility of subjects for epidemiologic and clinical lupus studies. These criteria may exclude patients with limited disease, restricting the generalizability of research findings. We developed and evaluated the ability of a weighted classification system to identify a broader spectrum of patients with lupus. Methods. We constructed the Boston Weighted Criteria system for the classification of SLE, updating that developed in 1984. Using a hospital billing database, we identified 271 patients seen in our rheumatology clinic for possible SLE and reviewed medical records for all ACR criteria and the treating rheumatologist's diagnosis. We compared both the Boston Criteria and the treating rheumatologist's diagnosis to the updated 1982 ACR criteria; we also compared the Boston Criteria to the treating rheumatologist's diagnosis. Results. The Boston Criteria identified 190/271 patients as having SLE, the rheumatologist's diagnosis identified 179/271, and the ACR criteria identified 171/271. The Boston Criteria had a sensitivity of 93% and specificity of 69% compared to the ACR criteria, and would identify 7% more patients. Conclusion. The Boston Criteria identify a larger number of patients compared with the current ACR criteria, while retaining face validity. This reflects the inclusion of patients with objective findings of SLE but less than 4 ACR criteria. Our Boston Criteria system could minimize selection bias and increase the generalizability of clinical SLE studies. C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Robert B Brigham Arthrit & Musculoskeletal Dis Cl, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Costenbader, KH (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, 55 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [T32-AR07258-23, K08AR02074-0, P01AR36308] NR 28 TC 30 Z9 35 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2002 VL 29 IS 12 BP 2545 EP 2550 PG 6 WC Rheumatology SC Rheumatology GA 621YK UT WOS:000179618400013 PM 12465149 ER PT J AU Pullman-Mooar, S Mooar, P Sieck, M Clayburne, G Schumacher, HR AF Pullman-Mooar, S Mooar, P Sieck, M Clayburne, G Schumacher, HR TI Are there distinctive inflammatory flares after hylan G-F 20 intraarticular injections? SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE hyaluronic acid injections; viscosupplementation; crystals; osteoarthritis inflammation; hylan G-F 20 ID KNEE OSTEOARTHRITIS; HYALURONAN; VISCOSUPPLEMENTATION; HYALGAN(R); TRIAL AB Objective. This survey was designed to examine features of a group of patients with acute painful joint effusions following hylan G-F 20 (Synvisc(C)) knee injections. Methods. Eight patients with painful local reactions after intraarticular hylan G-F 20 injections for knee ostcoarthritis were evaluated clinically, with detailed synovial fluid analysis, and followed for outcome. Results. Leukocyte counts ranged from 3150 to 103,000/mm(3). Crystals were seen in one patient. Inflammatory knee effusions occurred from I to 48 h after injections, but never with first injections. Synovial fluid volumes were 30 to 71 mm(3). Three patients had shiny clumps (not further characterized) that were noted in leukocytes on Wright stained smears. Most patients were treated with aspiration and depot steroids. Five of the,8 patients had moderate or greater improvement at 6 months. Conclusion. The majority of the occasional dramatic episodes of inflammation after hylan G-F 20 injection do not seem to be related to crystals. No detrimental lasting results were noted. The absence of post-hylan flares following the first intraarticular injection in this small series suggests that sensitization to or accumulation of hylan G-F 20 or its breakdown products may play an etiologic role in these flares. C1 Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Med Coll Penn & Hahnemann Univ, Sch Med, Philadelphia, PA 19102 USA. RP Pullman-Mooar, S (reprint author), Vet Affairs Med Ctr, 151,Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 15 TC 34 Z9 34 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2002 VL 29 IS 12 BP 2611 EP 2614 PG 4 WC Rheumatology SC Rheumatology GA 621YK UT WOS:000179618400025 PM 12465161 ER PT J AU Pollack, MH Penava, SA Bolton, E Worthington, JJ Allen, GL Farach, FJ Otto, MW AF Pollack, MH Penava, SA Bolton, E Worthington, JJ Allen, GL Farach, FJ Otto, MW TI A novel cognitive-behavioral approach for treatment-resistant drug dependence SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE illicit drug use; behavior therapy; cognitive therapy; treatment-resistant; opiate dependence; sex differences ID DETOXIFIED OPIATE ADDICTS; ALCOHOL CUE REACTIVITY; METHADONE-MAINTENANCE; COCAINE ABSTINENCE; GENDER DIFFERENCES; SENSATION SEEKING; OPIOID DEPENDENCE; SUBSTANCE-ABUSE; SEVERITY INDEX; HEROIN-ADDICTS AB Despite the application of treatments that combine methadone administration, weekly counseling, and contingency reinforcement strategies,many opiate-dependent patients continue illicit drug use. In this controlled study we piloted a novel cognitive-behavioral treatment (CBT) designed to reduce illicit drug use among patients receiving methadone treatment.-The treatment targeted the reduction of sensitivity to interoceptive cues associated with drug craving, and trained alternative responses to these cues. Patients (N = D) were randomly assigned to either this novel CBT program or a program of increased counseling, such that the two-programs of treatment were equated for therapist contact, assessment time, and contingency-reinforcement strategies. We found that, compared to a doubling of contact with their outpatient counselor, the,new program was associated with significantly greater reductions in illicit drug use for women, but not for men. Reasons for differential performance by women and men and future directions for this new treatment are discussed. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Habit Management Inst, Boston, MA 02118 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC-812,15 Parkman St, Boston, MA 02114 USA. FU NIDA NIH HHS [R21 DA10040-02] NR 45 TC 32 Z9 32 U1 5 U2 11 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 DEC PY 2002 VL 23 IS 4 BP 335 EP 342 AR PII S0740-5472(02)00298-2 DI 10.1016/S0740-5472(02)00298-2 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 631CV UT WOS:000180150500009 PM 12495795 ER PT J AU Garnick, DW Lee, MT Chalk, M Gastfriend, D Horgan, CM McCorry, F McLellan, AT Merrick, EL AF Garnick, DW Lee, MT Chalk, M Gastfriend, D Horgan, CM McCorry, F McLellan, AT Merrick, EL TI Establishing the feasibility of performance measures for alcohol and other drugs SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE performance; identification; engagement; initiation; measurement ID UNITED-STATES; INSURANCE; PREVALENCE AB The Washington Circle (a multi-disciplinary group of providers, researchers, managed care representatives, and public policy representatives) examined three performance measures for alcohol and other drug (AOD) services. These measures, which were developed and applied to managed care organizations' administrative data for their commercial enrollees, are: (a) identification, the percent of adult enrollees with AOD diagnoses; (b) initiation, the percent of adults with an inpatient AOD admission or with an, index outpatient visit for AOD abuse or dependence and any additional AOD services within 14 days of identification; and (c) engagement, the percent of adults diagnosed with, AOD disorders that. receives two additional AOD services within 30 days of the initiation of dare. We conclude that using administrative databases to compare managed care organizations' performance is feasible, meaningful and informative. The article discusses issues in interpreting performance measures in several areas: organizational structure of alcohol and other drug services, information available for measurement, and computational issues. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Brandeis Univ, Heller Sch Social Policy & Management, Schneider Inst Hlth Policy, Waltham, MA 02454 USA. Ctr Subst Abuse Treatment, Div Serv Improvement, Rockville, MD 20857 USA. Massachusetts Gen Hosp, Addict Res Program, Boston, MA 02115 USA. New York Off Alcoholism & Subst Abuse Serv, Clin Serv, New York, NY 10018 USA. Treatment Res Inst, Philadelphia, PA 19106 USA. RP Garnick, DW (reprint author), Brandeis Univ, Heller Sch Social Policy & Management, Schneider Inst Hlth Policy, 415 South St, Waltham, MA 02454 USA. RI Garnick, Deborah/I-9009-2012 NR 29 TC 78 Z9 78 U1 0 U2 5 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 DEC PY 2002 VL 23 IS 4 BP 375 EP 385 AR PII S0740-5472(02)00303-3 DI 10.1016/S0740-5472(02)00303-3 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 631CV UT WOS:000180150500014 PM 12495800 ER PT J AU Gonzalez, S Tannous, Z AF Gonzalez, S Tannous, Z TI Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SCANNING LASER MICROSCOPY; IN-VIVO; HUMAN SKIN; HISTOLOGY AB Background. Real-time, near-infrared confocal laser scanning microscopy may provide a way to diagnose basal cell carcinoma in vivo and might potentially eliminate the need for invasive diagnostic biopsies in the future. Objective: The purpose of this study is to define the in vivo histologic features of basal cell carcinoma by using a high-resolution imaging technique. Methods: Five fair-skinned white patients with 8 basal cell carcinoma lesions were recruited for this study. Near-infrared reflectance confocal microscopy imaging was used to characterize the histologic features of these lesions in vivo. Subsequently, the confocal histologic features were correlated with the corresponding routine hematoxylin-and-eosin-stained sections obtained from invasive biopsies. Results: A uniform population of basal cell carcinoma cells with characteristic elongated nuclei oriented along the same axis was always present. Abundant blood vessels demonstrating prominent tortuosity were seen, as well as prominent, predominantly mononuclear inflammatory infiltrate admixed or in close apposition with basal cell carcinoma cells. Trafficking of leukocytes was visualized in real time. Conclusion: Our results demonstrate that near-infrared confocal microscopy may facilitate diagnosis of basal cell carcinoma with the use of in vivo high-resolution confocal features. Accuracy studies to evaluate these in vivo histologic criteria are warranted. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Gonzalez, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, Bartlett Hall 814,55 Blossom St, Boston, MA 02114 USA. NR 14 TC 140 Z9 142 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2002 VL 47 IS 6 BP 869 EP 874 DI 10.1067/mjd.2002.124690 PG 6 WC Dermatology SC Dermatology GA 619UY UT WOS:000179496900008 PM 12451371 ER PT J AU Karlawish, JHT Casarett, DJ James, BD AF Karlawish, JHT Casarett, DJ James, BD TI Alzheimer's disease patients' and caregivers' capacity, competency, and reasons to enroll in an early-phase Alzheimer's disease clinical trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; research ethics; informed consent; decision-making capacity; competency ID INFORMED CONSENT; DEMENTIA; SAFETY AB OBJECTIVES: To examine the capacity, competency, and reasons for enrolling of patients with Alzheimer's disease (AD) and of their caregivers in an early phase AD clinical trial. DESIGN: Interviews were conducted with patients with AD, nondemented older persons, and caregivers. SETTING: Participants' homes. PARTICIPANTS: Fifteen patients with mild to moderate AD, 15 age- and education-matched nondemented older persons, and 15 patient caregivers. MEASUREMENTS: Capacity was measured using the MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR); a study coordinator who reviewed audiotapes of the capacity interviews judged competency, and the reasons for a decision were determined by coding the capacity interviews. RESULTS: On all measures except the ability to make a choice, patients performed worse than controls (understanding: z = 3.2, P = .001; appreciation: z = 2.8, P = .005; reasoning: z = 3.5, P = .0005), and caregivers (understanding: z = 3.8, P = .0002; appreciation: z = 3.0, P = .003; reasoning: z = 3.6, P = .0003). Using the controls' performance to set psychometric criteria to define capacity, the proportions of patients with adequate understanding, appreciation, and reasoning were six of 15 (40%), three of 15 (20%), and five of 15 (33%). All caregivers and nine of the 15 (60%) patients were competent. Reasons for enrolling typically featured the potential benefit to the patients' health or well-being and altruism that was expressed as a desire to help other patients and their families or a desire to contribute to scientific knowledge. CONCLUSIONS: The MacCAT-CR, in particular its understanding scale, is a reliable and valid way to assess patient capacity and competency to enroll in an early-phase clinical trial. Although many patients have significant impairments in their capacity, some mild-stage patients are competent. Reasons for enrolling in an early-phase trial blend an expectation of therapeutic benefit and a desire to help others. C1 Univ Penn, Dept Med, Div Geriatr, Philadelphia, PA 19104 USA. Alzheimers Dis Ctr, Philadelphia, PA USA. Ctr Bioeth, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Karlawish, JHT (reprint author), 3615 Chestnut St, Philadelphia, PA 19104 USA. FU NIA NIH HHS [K01-AG00931, P30-AG01024] NR 28 TC 67 Z9 67 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2002 VL 50 IS 12 BP 2019 EP 2024 DI 10.1046/j.1532-5415.2002.50615.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 624EM UT WOS:000179747400015 PM 12473015 ER PT J AU Casarett, DJ Hirschman, KB Miller, ER Farrar, JT AF Casarett, DJ Hirschman, KB Miller, ER Farrar, JT TI Is satisfaction with pain management a valid and reliable quality indicator for use in nursing homes? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pain management; satisfaction; nursing homes ID GERIATRIC DEPRESSION SCALE; PATIENT SATISFACTION; RESIDENTS; PREVALENCE; ADULTS; SAMPLE; CARE AB OBJECTIVES: To determine whether satisfaction with pain management can be measured reliably in nursing homes and to gather preliminary data about the validity of satisfaction assessments in this population. DESIGN: Cross-sectional interview study. SETTING: Two urban nursing homes. PARTICIPANTS: Sixty-six nursing home residents with pain. MEASUREMENTS: Overall satisfaction with pain management, satisfaction with pain medication, experiences related to pain management, cognitive function, depressive symptoms, and retest reliability of overall satisfaction rating. RESULTS: Most residents (60/66; 91%) could rate their overall satisfaction with pain management. Overall satisfaction was weakly correlated with pain severity at the time of the interview (Spearman correlation coefficient = -0.28; P = .033) and over the past week (-0.27; P = .038). Overall satisfaction was also negatively associated with the Geriatric Depression Scale score (-0.50; P < .001). Satisfaction with pain medication was associated with several ratings of the medication's beneficial effects, including improved activity, sleep, and speed of relief, but not with the frequency with which it caused side effects. Ratings of overall satisfaction showed good reliability overall (kappa = 0.62; P < .001) and for those with Mini-Mental State Examination scores greater than 21 (kappa = 0.70; P < .001) and 21 or less (kappa = 0.54; P = .004). CONCLUSION: These results suggest that satisfaction with pain management can be measured reliably when residents are able to report their pain, but further research is needed before satisfaction with pain management can be incorporated into routine assessments in nursing homes. C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Div Geriatr Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Social Work, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Casarett, DJ (reprint author), 3615 Chestnut St, Philadelphia, PA 19104 USA. RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 NR 27 TC 7 Z9 7 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2002 VL 50 IS 12 BP 2029 EP 2034 DI 10.1046/j.1532-5415.2002.50617.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 624EM UT WOS:000179747400017 PM 12473017 ER PT J AU Bahlmann, EB McQuillan, BM Handschumacher, MD Chow, CM Guerrero, JL Picard, MH Weyman, AE Scherrer-Crosbie, M AF Bahlmann, EB McQuillan, BM Handschumacher, MD Chow, CM Guerrero, JL Picard, MH Weyman, AE Scherrer-Crosbie, M TI Effect of destructive pulse duration on the detection of myocardial perfusion in myocardial contrast echocardiography: In vitro and in vivo observations SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID CORONARY STENOSIS; B-MODE; MICROBUBBLES; ULTRASOUND AB Myocardial perfusion is detected with contrast echocardiography by comparing a contrast-enhanced image with a baseline obtained before contrast injection (true baseline) or after myocardial bubble destruction after a high-power destructive pulse (postdestructive pulse baseline). Although it is assumed that all bubbles are destroyed by a destructive pulse insuring optimal contrast detection, this assumption has not been tested. In 18 participants we compared the videointensity (VI) differences among the contrast-enhanced image, the postdestructive pulse baseline, and the true baseline using both triggered high-mechanical index imaging and real-time imaging. VI difference was significantly greater for the true baseline with both techniques at all ventricular levels. The benefit of using a true baseline was less when the duration of the destructive pulse was increased. Similarly, we quantified VI in a flow phantom using continuous Optison (commercially available perfluoropropane-filled albumin microbubbles) (Amersham, Princeton, NJ) infusion and variable durations of destructive pulses. VI decreased with the duration of the destructive pulse and reached a plateau after a duration of 8 to 15 frames. The plateau reached after a long destructive pulse was dependent on flow rate and concentration and never reached a true baseline, unless concentration (<100 muL/L) and flow rate (<0.5 cm/s) were very low. In conclusion: (1) in clinical studies, the difference in VI between contrast-enhanced and baseline images is greater when true baseline is used; (2) the longer the destructive pulse, the closer the postdestructive pulse baseline to true baseline; and (3) this effect exists in all regions of the left ventricle. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, VBK 5,55 Fruit St, Boston, MA 02114 USA. RI McQuillan, Brendan/B-8271-2013; OI McQuillan, Brendan/0000-0002-2130-8114; Picard, Michael/0000-0002-9264-3243 NR 12 TC 9 Z9 9 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 2002 VL 15 IS 12 BP 1440 EP 1447 DI 10.1067/mje.2002.126166 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 626DC UT WOS:000179856200004 PM 12464909 ER PT J AU Lowe, HC Mac Neill, BD Van de Werf, F Jang, IK AF Lowe, HC Mac Neill, BD Van de Werf, F Jang, IK TI Pharmacologic reperfusion therapy for acute myocardial infarction SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Review DE myocardial infarction; reperfusion; thrombolysis ID TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE CORONARY SYNDROMES; GLYCOPROTEIN IIB/IIIA INHIBITION; INTRAVENOUS THROMBOLYTIC THERAPY; OPTICAL COHERENCE TOMOGRAPHY; DIRECT THROMBIN INHIBITORS; FACTOR PATHWAY INHIBITOR; BLIND RANDOMIZED TRIAL; FIBRINOLYTIC THERAPY; RECEPTOR BLOCKADE AB Acute myocardial infarction (MI) remains a significant problem in terms of morbidity, mortality and healthcare costs. Pharmacologic reperfusion therapies for MI are becoming increasingly complex. This review therefore places contemporary pharmacologic MI developments into perspective. An historical overview of pharmacologic reperfusion therapy for MI is provided, followed by an analysis of current limitations, treatment options, and present and likely future pharmacologic therapies. Adjunctive percutaneous and other treatments are also discussed, to clarify what is becoming a rapidly changing field. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bullfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 155 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD DEC PY 2002 VL 14 IS 3 BP 179 EP 196 DI 10.1023/A:1025050208649 PG 18 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 708BC UT WOS:000184545800001 PM 12913398 ER PT J AU Gibson, CM de Lemos, JA Murphy, SA Marble, SJ Dauterman, KW Michaels, A Barron, HW Antman, EM AF Gibson, CM de Lemos, JA Murphy, SA Marble, SJ Dauterman, KW Michaels, A Barron, HW Antman, EM CA TIMI Study Grp TI Methodologic and clinical validation of the TIMI myocardial perfusion grade in acute myocardial infarction SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE TIMI myocardial perfusion grade; TIMI flow grade; acute MI; thrombolysis ID LEFT-VENTRICULAR FUNCTION; ST-SEGMENT ELEVATION; FOLLOW-UP; SUCCESSFUL THROMBOLYSIS; ANGIOPLASTY; REPERFUSION; FLOW; RESOLUTION; PREDICTOR; ABCIXIMAB AB Improved microvascular perfusion using the TIMI myocardial perfusion grade (TMPG) has been related to reduced in hospital, 30-day and 2-year mortality following thrombolytic administration. We sought to validate this measure using the more quantitative technique of digital subtraction angiography (DSA) and to correlate TMPG with ST segment resolution. DSA was used to analyze films from the LIMIT AMI acute myocardial infarction trial of front loaded r-tPA and rhuMAb CD18. Dye kinetics were also characterized using DSA in 88 arteries from patients without acute coronary syndromes in the absence of an obstructive lesion. Compared to normal patients, microvascular perfusion was reduced in acute myocardial infarction patients on DSA as demonstrated by a reduction in peak Gray (brightness) (p < 0.0001), the rate of rise in Gray/sec (p < 0.0001), the blush circumference (p < 0.0001), and the rate of growth in circumference (cm/sec) (p < 0.0001). However, while DSA perfusion was impaired overall in the setting of acute myocardial infarction, TMPG grade 3 in the setting of acute myocardial infarction did not differ from that in normal patients when studied quantitatively as shown by similar rates of growth in brightness and circumference (p = NS). ST resolution and the TMPG were significantly associated (p = 0.04). Compared to normal patients, acute myocardial infarction reduces the peak brightness of the myocardium, the rate of rise in brightness, the circumference of blush and the rate of growth in circumference as assessed using digital subtraction angiography. However, acute myocardial infarction patients with TMPG 3 had rates of growth in brightness and circumference that were nearly identical to normal patients. Thus, DSA validates that TMPG 3 is associated with normal kinetics of myocardial perfusion, and this likely accounts for the low (0.7%) 30 day mortality observed among those patients with TFG 3 and TMPG 3. C1 Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. Univ Texas, Dept Med, SW Med Ctr, Dallas, TX USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Calif San Francisco, Dept Med, Div Cardiovasc, San Francisco, CA USA. RP Gibson, CM (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 15 TC 16 Z9 16 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD DEC PY 2002 VL 14 IS 3 BP 233 EP 237 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 708BC UT WOS:000184545800007 PM 12913404 ER PT J AU Weber, JE Hollander, JE Murphy, SA Braunwald, E Gibson, CM AF Weber, JE Hollander, JE Murphy, SA Braunwald, E Gibson, CM TI Quantitative comparison of coronary artery flow and myocardial perfusion in patients with acute myocardial infarction in the presence and absence of recent cocaine use SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE TIMI myocardial perfusion grade; TIMI flow grade; TIMI frame count; cocaine; myocardial infarction ID TISSUE-PLASMINOGEN-ACTIVATOR; THROMBOLYSIS; TRIAL; THROMBOSIS; ABUSE; MORTALITY; DISEASE AB Background: Numerous factors have been implicated in the pathogenesis of cocaine associated myocardial infarction (CAMI). However, the relative contributions each of these mechanisms provide to the pathogenesis of CAMI have not been well defined. We hypothesized that significant angiographic differences exist between CAMI patients vs thrombotic AMI patients (TAMI) and normal controls. Methods: The TIMI Flow Grade, corrected TIMI Frame Count (CTFC), TIMI Myocardial Perfusion Grade (TMPG), presence of triple-vessel disease, stenosis severity, and presence of angiographically apparent thrombus were compared in patients who sustained CAMI to TAMI patients and normal controls. Results: 2,495 angiograms were analyzed (CAMI = 57, TAMI = 2,403, Controls = 35). Impairment in both epicardial and microvascular flow in patients with CAMI was intermediate between TAMI and controls. Compared to TAMI patients, CAMI patients were less likely to have 3 vessel disease (8.9% vs. 19.1%; p < 0.05), epicardial stenosis was less severe (14.9+/-30.2 vs. 72.6+/-18.6; p < 0.0001), less thrombus was present (6.5% vs. 33.1%; p < 0.001) and TIMI grade 3 flow was observed more frequently (76% vs. 59%). Normal TMPG 3 perfusion was significantly impaired in both CAMI and TAMI patients when compared to controls without AMI (TMPG 3 was 40% and 26.6% vs. 100% respectively; p < 0.001 for both). The majority of patients in both AMI groups had diminished or absent tissue level perfusion (TMPG 0 flow, CAMI 53.9 vs. TAMI 56.8%). Conclusions: Both epicardial and microvascular flow is impaired in CAMI. While epicardial flow among CAMI patients is slightly better than TAMI patients, the incidence of little or severely impaired tissue level perfusion is nearly identical. C1 Brigham & Womens Hosp, Dept Med, TIMI Data Coordinating Ctr, TIMI Study Grp, Boston, MA 02115 USA. Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA. Univ Michigan, Hurley Med Ctr, Dept Cardiol, Ann Arbor, MI 48109 USA. Hosp Univ Penn, Dept Emergency Med, Sch Med, Philadelphia, PA 19104 USA. RP Gibson, CM (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Data Coordinating Ctr, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. OI Hollander, Judd/0000-0002-1318-2785 NR 32 TC 8 Z9 11 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD DEC PY 2002 VL 14 IS 3 BP 239 EP 245 DI 10.1023/A:1025056912284 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 708BC UT WOS:000184545800008 PM 12913405 ER PT J AU Bromley, B Lieberman, E Shipp, TD Benacerraf, BR AF Bromley, B Lieberman, E Shipp, TD Benacerraf, BR TI Fetal nose bone length - A marker for Down syndrome in the second trimester SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE aneuploidy, second trimester; fetal nose bone length; marker, fetal Down syndrome; midsagittal profile; sonography ID MATERNAL AGE; FETUSES; TRISOMY-21; GESTATION; NASAL; 2ND-TRIMESTER AB Objective. To evaluate the significance of nasal bone length in relation to the detection of Down syndrome in the second trimester. Methods. We evaluated consecutive fetuses referred to our facility between 15 and 20 weeks' gestation for sonography and amniocentesis because of an increased risk of aneuploidy. A detailed structural survey, biometric measurements, and measurement of the nasal bone were obtained at the time of amniocentesis and subsequently compared with karyotype. The characteristics of the fetuses with Down syndrome were compared with those of the euploid fetuses. Results. A total of 239 fetuses were evaluated. Sixteen fetuses (7%) had Down syndrome, and 223 were euploid. In fetuses with Down syndrome, 6 (37%) of 16 did not have detectable nose bones, compared with 1 (0.5%) of 223 control fetuses, yielding a likelihood ratio of 83, Detectable nasal bones were seen in 10 fetuses with Down syndrome and 222 euploid fetuses. A receiver operating characteristic curve for the biparietal diameter-nasal bone length ratio showed that a value of 9 or greater detected 100% of fetuses with Down syndrome and 22% of euploid fetuses. If the ratio were 10 or greater, then 81% fetuses with Down syndrome and 11 % of euploid fetuses would have been identified, If the ratio were 11 or greater, 69% of fetuses with Down syndrome would be identified, compared with 5% of euploid fetuses. Conclusions. The absence of a nasal bone is a powerful marker for Down syndrome. A short nasal bone is associated with an increased likelihood for fetal Down syndrome in a high-risk population. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Bromley, B (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. NR 12 TC 80 Z9 85 U1 0 U2 3 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2002 VL 21 IS 12 BP 1387 EP 1394 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 623GX UT WOS:000179695900011 PM 12494981 ER PT J AU Smith, JJ Henderson, JA Baim, DS AF Smith, JJ Henderson, JA Baim, DS TI The Food and Drug Administration and reprocessing of single-use medical devices: A revised policy and new questions SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material DE catheters and catheterization; medical devices C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Ctr Integrat Med & Innovat Technol, Boston, MA USA. RP Smith, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St WACC 515S, Boston, MA 02114 USA. NR 13 TC 7 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2002 VL 13 IS 12 BP 1179 EP 1182 DI 10.1016/S1051-0443(07)61962-9 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 624LT UT WOS:000179761700001 PM 12471179 ER PT J AU Limon, A Nakajima, N Lu, R Ghory, HZ Engelman, A AF Limon, A Nakajima, N Lu, R Ghory, HZ Engelman, A TI Wild-type levels of nuclear localization and human immunodeficiency virus type 1 replication in the absence of the central DNA flap SO JOURNAL OF VIROLOGY LA English DT Article ID IN-VIVO; POLYPURINE TRACT; PREINTEGRATION COMPLEXES; LENTIVIRAL VECTORS; HIV-1 REPLICATION; MOLECULAR CLONE; RETROVIRAL DNA; GENE-TRANSFER; PLUS-STRAND; NEF GENE AB Numerous factors have been implicated in the nuclear localization of retroviral preintegration complexes. Whereas sequences in human immunodeficiency virus type 1 (HIV-1) matrix, Vpr, and integrase proteins were initially reported to function specifically in nondividing cells, other recently identified sequences apparently function in dividing cells as well. One of these, the central DNA flap formed during reverse transcription, is specific to lentiviruses. It was previously reported that flap-negative (F-) HIV-1(LAI) was completely defective for viral spread in the MT-4 T-cell line, yet F- HIV-1 vectors were only 2- to 10-fold defective in various single-round transduction assays. To address these different findings, we analyzed the infectivity and nuclear localization phenotypes of two highly related T-cell-tropic strains, HIV-1(NL4-3) and a derivative of HIV-1(HXBc2) deficient for both Vpr and Net In stark contrast to the previous report, F- derivatives of both strains replicated efficiently in MT-4 cells. F- HIV-1(NL4-3) also spread like wild-type HIV-1(NL4-3) in infected Jurkat and primary T-cell cultures. In contrast, F- HIV-1(HXBc2) was replication defective in primary T cells. Results of real-time quantitative PCR assays, however, indicated that F- HIV-1(HXBc2) entered primary T-cell nuclei as efficiently as its wild-type counterpart. Thus, the F- HIV-1(HXBc2) growth defect did not appear to correlate with defective nuclear import. Consistent with this observation, wild-type nef restored replication to F- HIV-1(HXBc2) in primary T cells. Our results indicate that the central DNA flap does not play a major role in either preintegration complex nuclear import or HIV-1 replication in a variety of cell types. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI28691, AI45313, P30 AI028691, R01 AI039394, R37 AI039394] NR 52 TC 79 Z9 81 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 DEC PY 2002 VL 76 IS 23 BP 12078 EP 12086 DI 10.1128/JVI.76.23.12078-12086.2002 PG 9 WC Virology SC Virology GA 612PB UT WOS:000179083700030 PM 12414949 ER PT J AU Day, CL Lauer, GM Robbins, GK McGovern, B Wurcel, AG Gandhi, RT Chung, RT Walker, BD AF Day, CL Lauer, GM Robbins, GK McGovern, B Wurcel, AG Gandhi, RT Chung, RT Walker, BD TI Broad specificity of virus-specific CD4(+) T-helper-cell responses in resolved hepatitis C virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; PRIMERS PCR-SSP; NONSTRUCTURAL PROTEIN-3; EFFECTOR FUNCTION; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; VIRAL CLEARANCE; DEFICIENT MICE; HLA-B; EPITOPES AB Vigorous virus-specific CD4(+) T-helper-cell responses are associated with successful control of hepatitis C virus (HCV) and other human viral infections, but the breadth and specificity of responses associated with viral containment have not been defined. To address this we evaluated the HCV-specific CD4(+) T-helper-cell response in HCV antibody-positive persons who lack detectable plasma viremia, and compared this response to that in persons with chronic HCV infection. Peripheral blood mononuclear cells were stimulated with HCV proteins, followed by measurement of HCV-specific CD4'-T-cell responses to a comprehensive set of overlapping HCV peptides by intracellular gamma interferon production. In three persons with resolved HCV infection studied in detail, 13 to 14 epitopes were targeted, but none was recognized by all three. The 37 defined epitopes were predominantly distributed among the HCV proteins core, NS3, NS4, and NS5. In an expanded analysis of responses to these proteins in persons with resolved infection, an average of 10 epitopes was targeted, whereas in persons with chronic viremia never was more than one epitope targeted (P < 0.001). This comprehensive analysis of the breadth and specificity of HCV-specific T-helper-cell responses indicates that up to 14 viral epitopes can be simultaneously targeted by circulating virus-specific CD4(+) T helper cells in a controlled human viral infection. Moreover, these data provide important parameters for evaluation of candidate HCV vaccines, and provide rationale for immunotherapy in chronic HCV infection. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ New England Med Ctr, Div Infect Dis, Boston, MA 02111 USA. Lemuel Shattuck Hosp, Boston, MA USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Rm 5212D, Charlestown, MA 02129 USA. RI Robbins, Gregory/F-7988-2011; Yang, Chen/G-1379-2010; Day, Cheryl/J-9844-2012 FU NIAID NIH HHS [AI 31563, R01 AI031563, T32 AI007387, T332 AI 07387-12]; NIDDK NIH HHS [DK 57857, R01 DK057857] NR 53 TC 180 Z9 188 U1 0 U2 3 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 DEC PY 2002 VL 76 IS 24 BP 12584 EP 12595 DI 10.1128/JVI.76.24.12584-12595.2002 PG 12 WC Virology SC Virology GA 617DE UT WOS:000179344800019 PM 12438584 ER PT J AU Hazzard, WR AF Hazzard, WR TI Geriatrics at the crossroads - or simply early in the journey? SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 Univ Washington, VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. RP Hazzard, WR (reprint author), Univ Washington, VA Puget Sound Healthcare Syst, S-GEC-182,4660 S Columbian Way, Seattle, WA 98108 USA. NR 2 TC 6 Z9 6 U1 2 U2 2 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 DEC PY 2002 VL 57 IS 12 BP M806 EP M806 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 625JL UT WOS:000179813300012 PM 12456742 ER PT J AU Warshaw, G AF Warshaw, G TI Geriatrics at the crossroads - or simply early in the journey? Commentary SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 Univ Washington, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. RP Warshaw, G (reprint author), Univ Cincinnati, Med Ctr, Off Geriatr Med, 231 Albert Sabin Way,POB 670504, Cincinnati, OH 45267 USA. NR 2 TC 6 Z9 6 U1 1 U2 2 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 DEC PY 2002 VL 57 IS 12 BP M806 EP M807 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 625JL UT WOS:000179813300013 PM 12456741 ER PT J AU Thurberg, BL Rennke, H Colvin, RB Dikman, S Gordon, RE Collins, AB Desnick, RJ O'Callaghan, M AF Thurberg, BL Rennke, H Colvin, RB Dikman, S Gordon, RE Collins, AB Desnick, RJ O'Callaghan, M TI Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy SO KIDNEY INTERNATIONAL LA English DT Article DE renal disease; Fabry disease; X-linked recessive disorder; neutral glycosphingolipids; renoprotection; end-stage renal disease; Phase 3 trial ID ATYPICAL VARIANT; RENAL CHANGES; DISEASE; TRANSPLANTATION; HYPERTROPHY; RECURRENCE; SAFETY AB Background. Fabry disease, a lysosomal storage disease caused by deficient lysosomal alpha-galactosidase A activity, is characterized by globotriaosylceramide (GL-3) accumulation in multiple cell types, particularly the vasculature, leading to end organ failure. Accumulation in the kidney is responsible for progressive decline in renal function in male patients with the classical phenotype, resulting in renal failure in their third to fifth decades of life. With the advent of recombinant protein synthesis technology, enzyme replacement therapy has become a viable alternative to dialysis or renal transplantation, previously the only available treatment options for end-stage renal disease. Methods. The pre- and post-treatment renal biopsies were analyzed from fifty-eight Fabry patients enrolled in a Phase 3 double-blind, randomized, placebo-controlled trial followed by a six-month open label extension study of the recombinant human enzyme, alpha-galactosidase A (r-halphaGalA), administered IV at 1 mg/kg biweekly. The purpose of this investigation was to detail the pathologic changes in glycosphingolipid distribution and the pattern of post-treatment clearance in the kidney. Results. Baseline evaluations revealed GL-3 accumulations in nearly all renal cell types including vascular endothelial cells, vascular smooth muscle cells, mesangial cells and interstitial cells, with particularly dense accumulations in podocytes and distal tubular epithelial cells. After 11 months of r-halphaGal A treatment there was complete clearance of glycolipid from the endothelium of all vasculature as well as from the mesangial cells of the glomerulus and interstitial cells of the cortex. Moderate clearance was noted from the smooth muscle cells of arterioles and small arteries. Podocytes and distal tubular epithelium also demonstrated evidence for decreased GL-3, although this clearance was more limited than that observed in other cell types. No evidence of immune complex disease was found by immunofluorescence despite circulating anti-r-halphaGalA IgG antibodies. Conclusions. These findings indicate a striking reversal of renal glycosphingolipid accumulation in the vasculature and in other renal cell types, and suggest that long-term treatment with r-halphaGalA may halt the progression of pathology and prevent renal failure in patients with Fabry disease. C1 Genzyme Corp, Dept Pathol, Cambridge, MA USA. Genzyme Corp, Dept Preclin Biol, Cambridge, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Mt Sinai Sch Med, Dept Human Genet, New York, NY USA. RP O'Callaghan, M (reprint author), Genzyme Corp, Dept Preclin Biol, POB 9322,1 Mt Rd, Framingham, MA 01701 USA. FU NCRR NIH HHS [5 MO1 RR00071]; NICHD NIH HHS [5 P30 HD28822]; NIDDK NIH HHS [R29 DK 34045] NR 42 TC 189 Z9 199 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2002 VL 62 IS 6 BP 1933 EP 1946 DI 10.1046/j.1523-1755.2002.00675.x PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 617DV UT WOS:000179346600002 PM 12427118 ER PT J AU Rincon-Choles, H Kasinath, BS Gorin, Y Abboud, HE AF Rincon-Choles, H Kasinath, BS Gorin, Y Abboud, HE TI Angiotensin II and growth factors in the pathogenesis of diabetic nephropathy SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 3rd International Conference on Hypertension and the Kidney CY FEB, 2002 CL MADRID, SPAIN SP Hosp Gen, Dept Nephrol, Univ Gregorio Maranon, Spanish Soc Nephrol, Spanish Soc Hypertens, European Renal Assoc, European Dialysis & Transplant Assoc, European Soc Hypertens DE renin-angiotensin system; progressive renal disease; capillary permeability; hemodynamics; fibrosis; AGEs; transforming growth factor-beta ID FACTOR-BETA; GLOMERULAR NEPHRIN; CONVERTING ENZYME; RENAL EXPRESSION; RATS; SYSTEM; RECEPTORS; KIDNEY; KINASE AB The renin-angiotensin system (RAS) and growth factors mediate structural and functional changes during the course of diabetic nephropathy (DN). Studies in humans and experimental models with DN suggest their involvement in the development and progression of DN. Activation of renal tissue RAS and increased expression of growth factors have been demonstrated at early stages of the disease. Angiotensin II and growth factors alter renal hemodynamics and exert trophic changes in renal cells that eventually result in fibrosis through direct mechanisms or through the release of other mediators. Their effects are likely modulated by metabolic changes including high glucose and free fatty acids. While blockade of the RAS ameliorates DN in humans, such evidence for blockade of growth factors is still lacking. It is likely that susceptibility to the development of DN and therapeutic efficacy are modulated by genetic polymorphisms in components of the RAS and growth factors including their receptors and other target molecules. Approaches to understand the intricate relationship between these systems and the mechanism(s) by which they alter capillary permeability and result in structural changes are areas of fruitful investigation. C1 Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Div Nephrol, Dept Med, San Antonio, TX USA. RP Rincon-Choles, H (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 33 TC 11 Z9 12 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2002 VL 62 SU 82 BP S8 EP S11 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 613AC UT WOS:000179106800003 ER PT J AU Kieff, DA Busaba, N AF Kieff, DA Busaba, N TI Treatment of isolated sphenoid sinus inflammatory disease by endoscopic sphenoidotomy without ethmoidectomy SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern-Section of the Triological-Society CY JAN 25-27, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Triol Soc, Eastern Sect DE sphenoid sinusitis; endoscopic sinus surgery; stereotactic guidance; mucocele; fungoma ID MANAGEMENT; DIAGNOSIS; SURGERY AB Objectives/Hypothesis. Isolated chronic sphenoid sinusitis is a rare entity. The study was conducted to determine the efficacy of endoscopic sinus surgery with partial middle turbinectomy and without ethmoidectomy in treating isolated sphenoid opacification from inflammatory and infectious disease. Study Design: Case series of 20 patients generated by retrospective review of 307 consecutive patients who underwent surgical treatment for chronic rhinosinusitis. Methods: The medical records were reviewed for pertinent demographic, symptom, radiographic, and endoscopic data preoperatively, interoperatively, and postoperatively. All patients in the series underwent computed tomographic image-guided endoscopic sphenoid sinus surgery with partial middle turbinectomy. Results: The study population consisted of 12 male and 8 female patients between 28 and 75 years of age. Headache (15 patients) and/or postnasal drip (14 patients) were the presenting symptoms in 17 of the patients. Three patients were asymptomatic. Surgical findings included inspissated secretions (15 patients), fungal debris (2 patients), and mucopyoceles (3 patients). The 17 patients with preoperative symptoms were symptom free by 12 weeks postoperatively and have remained so with follow-up ranging from 12 months to 3.25 years (mean follow-up, 23.1 mo). There were no operative complications in the series. Conclusions: Endoscopic sphenoid sinus surgery without ethmoidectomy is effective for treating isolated sphenoid sinus opacification associated with inflammatory or infectious sinus disease. Partial middle turbinectomy at the time of surgery facilitates the approach, as well as postoperative cleaning and surveillance. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kieff, DA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2002 VL 112 IS 12 BP 2186 EP 2188 DI 10.1097/00005537-200212000-00011 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 624JE UT WOS:000179755900011 PM 12461338 ER PT J AU Stone, ME AF Stone, ME TI The Dana guide to brain health. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD DEC PY 2002 VL 127 IS 20 BP 103 EP 103 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 624JT UT WOS:000179757100038 ER PT J AU Fossella, FV Lynch, T Shepherd, FA AF Fossella, FV Lynch, T Shepherd, FA TI Second line chemotherapy for NSCLC: establishing a gold standard SO LUNG CANCER LA English DT Article DE docetaxel; NSCLC; gold standard ID CELL LUNG-CANCER; PHASE-II TRIAL; 2ND-LINE TREATMENT; DOCETAXEL; GEMCITABINE; AGENTS AB When compared with best supportive care alone, the second-line treatment of non-small cell lung cancer (NSCLC) with 75 mg/m(2) docetaxel significantly improved the 1-year survival rate (37 vs. 12%) and lengthened time to disease progression (median 12.3 vs. 7.0 weeks) in study TAX 317. Quality of life was superior with docetaxel and the need for tumor-related therapy was reduced. Docetaxel 75 mg/m(2) in this setting is safe, and offers clinically meaningful benefit to patients. These findings are supported by data from study TAX 320 in which a heavily pre-treated population of advanced NSCLC patients was randomized to receive docetaxel 100 mg/m(2), docetaxel 75 mg/m(2) or a comparator arm of either vinorelbine or ifosfamide. Treatment with either dose of docetaxel significantly increased the proportion of patients without disease progression at 26 weeks. By intent to treat analysis, 1-year survival was 32% in patients randomized to docetaxel 75 mg/m(2). This was significantly greater than the 19% 1-year survival rate in the comparator arm. Prior exposure to pactitaxel did not lessen the response rate or survival advantage of docetaxel in this second-line setting. Future development is likely to lie in the combination of docetaxel with novel molecular-targeted agents such as EGFR tyrosine kinase inhibitors. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. RP Fossella, FV (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd,Box 432, Houston, TX 77030 USA. NR 28 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD DEC PY 2002 VL 38 SU 4 BP S5 EP S12 AR PII S0169-5002(02)00167-8 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 640CC UT WOS:000180668200002 ER PT J AU Ruvinsky, I Chertkov, O Borue, XV Agulnik, SI Gibson-Brown, JJ Lyle, SR Silver, LM AF Ruvinsky, I Chertkov, O Borue, XV Agulnik, SI Gibson-Brown, JJ Lyle, SR Silver, LM TI Genetics analysis of mouse mutations Abnormal feet and tail and rough coat, which cause developmental abnormalities and alopecia SO MAMMALIAN GENOME LA English DT Article ID T-HAPLOTYPES; BRACHYURY; MICE; COMPLEX; KINASES; DEFECTS; CSK; TCT AB Mutations in the mouse Brachyury (T) gene are characterized by a dominant reduction of tail length and recessive lethality. Two quantitative trait loci. Brachyury-modifier 1 and 2 (Brm1 and Brm2) are defined by alleles that enhance the short-tail Brachyury phenotype. Here we report on a genetic analysis of a visable dominant mutation Abnormal feet and tail (Aft) located in the vicinity of Brm1. Affected animals display kinky tails and syndactyly in the hindlimbs, both likely resulting from a defect in apoptosis. We observed an unusual genetic incompatibility between Aft and certain genetic backgrounds. We show that Aft and T are likely to interact genetically, since some double heterozygotes are tailless. In addition to the tail and hindlimb phenotypes. Aft-bearing mutants display characteristic late-onset skin lesions. We therefore tested for allelism between Aft and a closely linked recessive mutation rough coat (rc) and found that these two mutations are likely nonallelic. Our results provide a valuable resource for the study of mammalian skin development and contribute to the genetic analysis of Brachyury function. C1 Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Washington Univ, Dept Biol, St Louis, MO 63130 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. RP Ruvinsky, I (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 8, Boston, MA 02114 USA. FU NICHD NIH HHS [HD-20275] NR 32 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 2002 VL 13 IS 12 BP 675 EP 679 DI 10.1007/s00335-002-2191-6 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 634KE UT WOS:000180337900001 PM 12514744 ER PT J AU Ossipova, O He, X Green, J AF Ossipova, Olga He, Xi Green, Jeremy TI Molecular cloning and developmental expression of Par-1/MARK homologues XPar-1A and XPar-1B from Xenopus laevis SO MECHANISMS OF DEVELOPMENT LA English DT Article DE molecular cloning; developmental expression; Par-1/MARK homologues; Xenopus laevis; serine-threonine kinase AB Par-1 encodes a serine/threonine kinase that is involved in asymmetric segregation of cell fate determinants in Caenorhabditis elegans and Drosophila embryos. Recent biochemical studies indicate an association of PAR-1 with the Dishevelled protein and suggest a role in so-called canonical Wnt signaling ( Nat. Cell Biol. 3 ( 2001) 628). Here we describe two Xenopus laevis cDNAs, which encode PAR-1 homologues designated XPar-1A and XPar-1B. Structurally, XPar-1A and XPar-1B are closely related to rat MARK proteins and human Par-1A and Par-1Ba, respectively. XPar-1A and XPar-1B are expressed both maternally and zygotically in an indistinguishable pattern. In the egg and cleavage stage embryos their transcripts are enriched in the animal pole of the embryo. During blastula and gastrula stages, cells in the animal and marginal regions continue to express both genes uniformly. Expression progresses vegetally towards and then through the blastopore lip concomitantly with the movements of epiboly and gastrulation. With the onset of neurulation, XPar-1A and XPar-1B transcripts are restricted to the neurectoderm. At tailbud and tadpole stages they are detected in the head region, including brain, eyes, otic vesicles, cement gland, branchial arches as well as spinal cord and somites. Therefore, this analysis suggests that the Xenopus par-1 homologues XPar-1A and XPar-1B are expressed in frog embryos both maternally and zygotically in a restricted pattern and may play a role in establishing polarity in early embryos as well as in organogenesis during later stages of development. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Med Sch, Dept Genet, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Med Sch, Dept Neurol, Children Hosp, Div Neurosci, Boston, MA 02115 USA. RP Green, J (reprint author), Harvard Med Sch, Dept Genet, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM jeremy_green@dfci.harvard.edu RI Green, Jeremy/F-3630-2010 OI Green, Jeremy/0000-0002-6102-2620 FU NICHD NIH HHS [HD 36345] NR 23 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 2002 VL 119 SU 1 BP S143 EP S148 AR PII S0925-4773(03)00107-2 DI 10.1016/S0925-4773(03)00107-2 PG 6 WC Developmental Biology SC Developmental Biology GA V43QV UT WOS:000202950500023 PM 14516676 ER PT J AU Glassman, PA Simon, B Belperio, P Lanto, A AF Glassman, PA Simon, B Belperio, P Lanto, A TI Improving recognition of drug interactions - Benefits and barriers to using automated drug alerts SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Annual Meeting of the VA HSR&D CY FEB, 2002 CL WASHINGTON, D.C. DE drug therapy; computer assisted; medication errors; attitude of health personnel; attitude toward computers; medical record systems; computerized ID DECISION-SUPPORT SYSTEMS; PHYSICIAN ORDER ENTRY; MEDICATION ERRORS; COMPUTER; CARE; EVENTS; INTERVENTION; IMPLEMENTATION; SATISFACTION; KNOWLEDGE AB BACKGROUND. Clinicians' perceptions about decision support systems may impact the effectiveness of these technologies. OBJECTIVE. To explore clinicians' baseline knowledge of common drug interactions and experiences with automated drug alerts within a provider order entry system as a means to better understand the potential benefits and barriers to using this technology. RESEARCH DESIGN. Cross-sectional survey. SUBJECTS. The study population comprised 263 clinicians practicing within a Southern California Veterans Affairs health care system that used VA's Computerized Patient Record System (CPRS). Response rate was 64%. MEASURES. A 67-item survey (19 questions) was developed to elicit information including: (1) computer use for patient-related activities; (2) recognition of drug interactions; and (3) benefits and barriers to using automated drug alerts. RESULTS. Clinicians correctly categorized 44% (range 11-64%) of all drug-drug pairs, 53% of interacting combinations, and 54% of contraindicated pairs. Providers also correctly categorized 55% (range 24-87%) of 11 drug-disease pairs and 62% of interacting combinations, and 53% of contraindicated pairs. Nearly 90% of clinicians thought drug alerts would be helpful to identify interactions yet 55% of clinicians perceived that the most significant barrier to utilizing existing alerts was poor signal to noise ratio, meaning too many nonrelevant warnings. CONCLUSIONS. Automated drug interaction alerts have the potential to dramatically increase clinicians' recognition of selected drug interactions. However, perceived poor specificity of drug alerts may be an important obstacle to efficient utilization of information and may impede the ability of such alerts to improve patient safety. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med 111G, VA HSR&D Ctr Excellence Study Healthcare Provider, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, VA HSR&D Ctr Excellence Study Healthcare Provider, Sepulveda, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Glassman, PA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med 111G, VA HSR&D Ctr Excellence Study Healthcare Provider, W Los Angeles Campus,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 40 TC 151 Z9 155 U1 3 U2 12 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 DEC PY 2002 VL 40 IS 12 BP 1161 EP 1171 DI 10.1097/01.MLR.0000036429.31445.E0 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 621ZM UT WOS:000179621500004 PM 12458299 ER PT J AU Swarztrauber, K Vickrey, BG Mittman, BS AF Swarztrauber, K Vickrey, BG Mittman, BS TI Physicians' preferences for specialty involvement in the care of patients with neurological conditions SO MEDICAL CARE LA English DT Article DE physician's practice patterns; referral and consultation; knowledge ID PARKINSONS-DISEASE; CAROTID ENDARTERECTOMY; REFERRAL RATES; UNITED-STATES; MANAGED-CARE; FINANCIAL INCENTIVES; MEDICAL OUTCOMES; STROKE PATIENTS; CONSULTATION; PATTERNS AB BACKGROUND. Recent changes in the US health care system have produced questions about the appropriate roles and responsibilities of generalist and specialist physicians within a primary care-centered health care delivery system. OBJECTIVES. To determine neurologists' and primary care physicians' preferences for specialist involvement in the management of common neurologic conditions and the factors influencing these preferences. RESEARCH DESIGN AND SUBJECTS. A self administered questionnaire was developed with the assistance of a multispecialty Advisory Board and sent to a stratified probability sample of 608 family physicians, 624 general internists, and 492 neurologists. MEASURES. The questionnaire contained three clinical scenarios, each followed by questions regarding respondent preferences for the primary care physician to manage alone, curb-side, or refer to a specialist. The questionnaire also contained knowledge questions corresponding to each scenario and physician and practice characteristics questions. RESULTS. Response rate was 60%. For all three scenarios, primary care physicians' preferences to involve a specialist differed substantially from neurologists' preferences, with nearly all neurologists preferring involvement of a specialist. Primary care physicians with less knowledge were more likely to prefer assistance from a neurologist. Physician age and practice setting influenced the type of assistance preferred (curbside vs. referral). Utilization management techniques and financial incentives had little influence on physician preferences to involve a specialist. CONCLUSIONS. The extensive disagreement between primary care physicians' and specialists' preferences for specialty involvement represents cause for considerable concern, supporting further efforts to identify where inappropriate referral processes are occurring and to implement mechanisms for improving the coordination and quality of primary and specialty care. C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Dept Neurol, Portland, OR USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Alzheimers Dis Res Ctr, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. RP Swarztrauber, K (reprint author), Oregon Hlth Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code L-226, Portland, OR 97201 USA. NR 71 TC 17 Z9 17 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2002 VL 40 IS 12 BP 1196 EP 1209 DI 10.1097/01.MLR.0000036601.97980.7C PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 621ZM UT WOS:000179621500007 PM 12458302 ER PT J AU Korthuis, PT Asch, S Mancewicz, M Shapiro, MF Mathews, WC Cunningham, WE McCutchan, JA Gifford, A Lee, ML Bozzette, SA AF Korthuis, PT Asch, S Mancewicz, M Shapiro, MF Mathews, WC Cunningham, WE McCutchan, JA Gifford, A Lee, ML Bozzette, SA TI Measuring medication - Do interviews agree with medical record and pharmacy data? SO MEDICAL CARE LA English DT Article DE HIV disease/AIDS; medications; cohort studies; methodology; epidemiology ID NATIONAL PROBABILITY SAMPLES; LOW-PREVALENCE DISEASES; SERVICES UTILIZATION; UNITED-STATES; HIV COST; ANTIRETROVIRAL THERAPY; ENDOMETRIAL CANCER; PRIMARY-CARE; LOW KAPPA; INFORMATION AB BACKGROUND. Medication measurement is crucial in assessing quality for chronic conditions yet agreement of alternate data sources remains uncertain. OBJECTIVES. To evaluate medication agreement between interviews, medical records, and pharmacy data; to assess data source contribution to attributing medication exposure; and to describe the impact of combining data sources on models that predict medication use. RESEARCH DESIGN. Prospective cohort study. SUBJECTS. Probability sample of HIV infected participants in the HIV Cost and Services Utilization Study. MEASURES. Medications reported in 2267 interviews, 1936 medical records, and 457 pharmacy records were compared using crude agreement, kappa, and the proportion of average positive and negative agreement. The percent of medications reported in each source alone was used to assess their relative contri- bution to attributing exposure status. We performed weighted logistic regression in alternate data sources. RESULTS. Kappa varied from 0.38 for nucleoside reverse transcriptase inhibitors to 0.70 for protease inhibitors, when comparing drug classes in interview versus medical record, interview versus pharmacy data, and medical record versus pharmacy data. The percentage of medications reported in medical records was greater than that reported in interviews or pharmacy data. Pharmacy data contributed little to the attribution of medication exposure. Adding medication data to interview data did not appreciably change analytic models predicting medication use. combining data sources does not change the results of analytic models predicting appropriate medication use.CONCLUSIONS. For specific medications, agreement between alternative data sources is fair to substantial, but is lower for key drug classes. Relying on one data source may lead to misclassification of drug exposure status, but combining data sources does not change the results of analytic models predicting appropriate medication use. C1 Univ Calif Los Angeles, Greater Los Angeles VA Syst, Los Angeles, CA 90073 USA. RAND Corp, Hlth Program, Santa Monica, CA 90407 USA. Univ Calif San Diego, San Diego, CA 92103 USA. San Diego VA Hlth Care Syst, San Diego, CA USA. Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. RP Korthuis, PT (reprint author), Univ Calif Los Angeles, Greater Los Angeles VA Syst, Bldg 500,Room 3233,11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. RI Mathews, William/E-4451-2010 OI Mathews, William/0000-0002-2352-0725 FU AHRQ HHS [U01 HS 08578] NR 33 TC 19 Z9 19 U1 0 U2 1 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 DEC PY 2002 VL 40 IS 12 BP 1270 EP 1282 DI 10.1097/01.MLR.0000036406.61316.B5 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 621ZM UT WOS:000179621500013 PM 12458308 ER PT J AU Cooper, RA Spaeth, DM Jones, DK Boninger, ML Fitzgerald, SG Guo, SF AF Cooper, RA Spaeth, DM Jones, DK Boninger, ML Fitzgerald, SG Guo, SF TI Comparison of virtual and real electric powered wheelchair driving using a position sensing joystick and an isometric joystick SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE wheelchair; controls; human-machine interface; human performance; virtual reality AB There are limited interface options for electric powered wheelchairs, which results in the inability of some individuals to drive independently. In addition, the development of new interface technologies will necessitate the development of alternative training methods. This study compares a conventional position sensing joystick to a novel isometric joystick during a driving task in a virtual environment and a real environment. The results revealed that there were few differences in task completion time and rootmean-square error (RMSE) between the two types of joysticks. There were significant correlations between the RMSE in the virtual environment and the real environment for both types of joysticks. The data indicate that performance in the virtual environment was representative of driving ability in the real environment, and the isometric joystick performed comparably to the position sensing joystick. (C) 2002 IPEM. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Bioengn & Phys Med & Rehabil, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Cent Michigan Univ, Dept Ind & Engn Technol, Mt Pleasant, MI 48859 USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, 5044 Forbes Tower, Pittsburgh, PA 15261 USA. OI Boninger, Michael/0000-0001-6966-919X NR 15 TC 29 Z9 29 U1 1 U2 3 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 DEC PY 2002 VL 24 IS 10 BP 703 EP 708 AR PII S1350-4533(02)00111-X DI 10.1016/S1350-4533(02)00111-X PG 6 WC Engineering, Biomedical SC Engineering GA 623TE UT WOS:000179718300008 PM 12460730 ER PT J AU Heneghan, C Flynn, J O'Keefe, M Cahill, M AF Heneghan, C Flynn, J O'Keefe, M Cahill, M TI Characterization of changes in blood vessel width and tortuosity in retinopathy of prematurity using image analysis SO MEDICAL IMAGE ANALYSIS LA English DT Article DE morphological processing; retinopathy of prematurity; segmentation; screening ID DIABETIC-RETINOPATHY; FILTERS AB Many retinal diseases are characterised by changes to retinal vessels. For example, a common condition associated with retinopathy of prematurity (ROP) is so-called plus disease, characterised by increased vascular dilation and tortuosity. This paper presents a general technique for segmenting out vascular structures in retinal images, and characterising the segmented blood vessels. The segmentation technique consists of several steps. Morphological preprocessing is used to emphasise linear structures such as vessels. A second derivative operator is used to further emphasise thin vascular structures, and is followed by a final morphological filtering stage. Thresholding of this image is used to provide a segmented vascular mask. Skeletonisation of this mask allows identification of points in the image where vessels cross (bifurcations and crossing points) and allows the width and tortuosity of vessel segments to be calculated. The accuracy of the segmentation stage is quite dependent on the parameters used, particularly at the thresholding stage. However, reliable measurements of vessel width and tortuosity were shown using test images. Using these tools, a set of images drawn from 23 subjects being screened for the presence of threshold ROP disease is considered. Of these subjects, I I subsequently required treatment for ROP, 9 had no evidence of ROP, and 3 had spontaneously regressed ROP. The average vessel width and tortuosity for the treated subjects was 96.8 mum and 1.125. The corresponding figures for the non-treated cohort were 86.4 mum and 1.097. These differences were statistically significant at the 99% and 95% significance level, respectively. Subjects who progressed to threshold disease during the course of screening showed an average increase in vessel width of 9.6 mum and in tortuosity of +0.008. Only the change in width was statistically significant. Applying a simple retrospective screening paradigm based solely on vessel width and tortuosity yields a screening test with a sensitivity and specificity of 82% and 75%. Factors confounding a more accurate test include poor image quality, inaccuracies in vessel segmentation, inaccuracies in measurement of vessel width and tortuosity, and limitations inherent in screening based solely on examination of the posterior pole. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Natl Univ Ireland Univ Coll Dublin, Dept Elect & Elect Engn, Dublin 4, Ireland. Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. Childrens Hosp, Dept Ophthalmol, Dublin 1, Ireland. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Heneghan, C (reprint author), Natl Univ Ireland Univ Coll Dublin, Dept Elect & Elect Engn, Dublin 4, Ireland. NR 31 TC 132 Z9 136 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 J9 MED IMAGE ANAL JI Med. Image Anal. PD DEC PY 2002 VL 6 IS 4 BP 407 EP 429 AR PII S1361-8415(02)00058-0 DI 10.1016/S1361-8415(02)00058-0 PG 23 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 623TG UT WOS:000179718500005 PM 12426111 ER PT J AU Franklin, ME Gonzalez, JJ AF Franklin, ME Gonzalez, JJ TI The endoluminal management of duodenal lesions SO MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES LA English DT Article DE endoluminal surgery; intraluminal surgery; laparoscopic surgery; laparoscopy; duodenal web; duodenal adenoma ID ASSISTED COLONOSCOPIC POLYPECTOMY; INTRAGASTRIC SURGERY; CYSTGASTROSTOMY AB Benign duodenal lesions such as adenomas and webs have traditionally been approached endoscopically. Unfortunately, endoscopic polypectomies are limited by the size and villous nature of the lesions as well as their locations within the lumen. Duodenal web resections may be restricted by the size of the opening leading to inadequate lumen size and recurrence. When these procedures fail, conventional open or laparoscopic surgery with its attendant morbidity is often necessary. Recent advances in camera optics and mini-laparoscopic instrumentation have expanded the laparoscopic options available to treat mucosal and submucosal lesions of the upper GI tract. Laparoscopic endoluminal surgery has evolved into a viable option for the treatment of many intragastric lesions. We have successfully extrapolated this concept to the treatment of proximal duodenal lesions. Successful resection of a duodenal web and a large tubulovillous adenoma are presented. Laparoendoscopic intraluminal management of benign duodenal lesions is safe, feasible, and effective. C1 UTHSC San Antonio, Texas Endosurg Inst, San Antonio, TX 78222 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Franklin, ME (reprint author), UTHSC San Antonio, Texas Endosurg Inst, 4242 E Southcross,Suite 1, San Antonio, TX 78222 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1364-5706 J9 MINIM INVASIV THER JI Minim. Invasive Ther. Allied Technol. PD DEC PY 2002 VL 11 IS 5-6 BP 297 EP 301 PG 5 WC Surgery SC Surgery GA 639VK UT WOS:000180649900015 ER PT J AU Weinstein, MH Signoretti, S Loda, M AF Weinstein, MH Signoretti, S Loda, M TI Diagnostic utility of immunohistochemical staining for p63, a sensitive marker of prostatic basal cells SO MODERN PATHOLOGY LA English DT Article DE basal cell; p63; high molecular weight; cytokeratin; prostate cancer ID P53 HOMOLOG; ANTIBODY 34-BETA-E12; EXPRESSION; CANCER; EPITHELIUM; PROLIFERATION; CULTURES; PROTEIN; BENIGN; LIMB AB Diagnostically reliable identification of prostatic basal cells has depended on staining for high molecular weight cytokeratin. The diagnosis of malignancy is often based on the absence of basal cells. False-negative staining is occasionally observed. Thus, a second method of identifying basal cells might prove useful. Selective expression of p63, a homologue of p53, has been demonstrated in prostatic basal cells. We investigated the diagnostic utility of p63 staining in 70 consecutive specimens for which the differential diagnosis included prostatic adenocarcinoma: 68 needle biopsies and 2 transurethral resection blocks. High molecular weight cytokeratin staining was the gold standard when material was available. A total of 61 specimens were diagnosed as carcinoma, 4 as atrophy, 2 as high-grade prostatic intraepithelial neoplasia, 2 as unclassified collections of benign glands, and 1 as carcinoma versus high-grade prostatic intraepithelial neoplasia. Sections mounted on charged slides were used for p63 staining for 14 specimens. Sections previously hematoxylin and eosin stained on uncharged slides were used for 56 specimens. In every case in which there was successful p63 staining (55 specimens), basal cells in benign lesions were properly marked and other cell types were not stained. Uninformative staining in the remaining 15 specimens was due to failure of tissue adherence in 14 specimens in which sections were on uncharged slides and, in I specimen, to poor positive internal control staining of benign glands. Thus, p63 staining was informative in 55 of 56 specimens (98%) for which there was material for examination. No case with satisfactory p63 and high molecular weight staining showed disagreement between the two stains. An additional group of 21 transurethral resection specimens was stained (p63 and high molecular weight cytokeratin). There was less false-negative staining for p63 compared with the case of high molecular weight cytokeratin. No false-positive staining was seen. We conclude that p63 staining is at least as sensitive and specific for the identification of basal cells in diagnostic prostate specimens as is high molecular weight cytokeratin staining. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weinstein, MH (reprint author), Wake Med Ctr, Dept Pathol, 3000 New Bern Ave, Raleigh, NC 27610 USA. FU NCI NIH HHS [R01-CA81755] NR 22 TC 78 Z9 80 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 DEC PY 2002 VL 15 IS 12 BP 1302 EP 1308 DI 10.1097/01.MP.0000038460.95912.6E PG 7 WC Pathology SC Pathology GA 629DC UT WOS:000180034300009 PM 12481011 ER PT J AU Malik, TH von Stechow, D Bronson, RT Shivdasani, RA AF Malik, TH von Stechow, D Bronson, RT Shivdasani, RA TI Deletion of the GATA domain of TRPS1 causes an absence of facial hair and provides new insights into the bone disorder in inherited tricho-rhino-phalangeal syndromes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; ZINC-FINGER PROTEIN; HEART TUBE FORMATION; DNA-BINDING DOMAIN; SYNDROME TYPE-I; NERVOUS-SYSTEM; ERYTHROID-DIFFERENTIATION; VENTRAL MORPHOGENESIS; HEMATOPOIETIC DEFECT; TARGETED DISRUPTION AB GATA transcription factors mediate cell differentiation in diverse tissues, and their dysfunction is associated with certain congenital human disorders. The six classical vertebrate GATA proteins, GATA-1 to GATA-6, are highly homologous, bear two tandem zinc fingers of the C, (GATA) type, and activate transcription. TRPS1, the only other vertebrate protein with the GATA motif, is a large, multitype zinc finger protein that harbors a single DNA-binding GATA domain and represses transcription. Monoallelic TRPS1 mutations cause two dominantly inherited human developmental disorders of the hair, face, and digits, tricho-rhino-phalangeal syndrome (TRPS) types I (MIM 190350) and III (MIM 190351); missense GATA domain mutations account for the more severe type III form. Here we report that heterozygous mice with deletions of the TRPS1 GATA domain (TRPS1(+/Deltagt)) display facial anomalies that overlap with findings for TRPS, whereas TRPS1(Deltagt/Deltagt) mice additionally reveal a complete absence of vibrissae. Unexpectedly, TRPS1(Deltagt/Deltagt) mice die of neonatal respiratory failure resulting from abnormalities of the thoracic spine and ribs. Heterozygotes also develop thoracic kyphoscoliosis with age and reveal structural deficits in cortical and trabecular bones. These findings directly implicate the GATA type zinc finger of TRPS1 in regulation of bone and hair development and suggest that skeletal abnormalities emphasized in descriptions of TRPS are only the extreme manifestations of a generalized bone dysplasia. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 1 Jimmy Fund Way, Boston, MA 02115 USA. NR 62 TC 51 Z9 56 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2002 VL 22 IS 24 BP 8592 EP 8600 DI 10.1128/MCB.22.24.8592-8600.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 620HF UT WOS:000179527400020 PM 12446778 ER PT J AU Vallejo, I Vallejo, M AF Vallejo, I Vallejo, M TI Pituitary adenylate cyclase-activating polypeptide induces astrocyte differentiation of precursor cells from developing cerebral cortex SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; CENTRAL-NERVOUS-SYSTEM; BONE MORPHOGENETIC PROTEINS; INHIBITORY FACTOR-RECEPTOR; ZONE PROGENITOR CELLS; PACAP RECEPTOR; MESSENGER-RNA; NEURONAL DIFFERENTIATION; CORTICAL PRECURSORS; TISSUE DISTRIBUTION AB Ciliary neurotrophic factor and bone morphogenetic proteins induce astrocytogenesis in the developing rat brain by stimulating STAT- and Smad-dependent signaling, respectively. We previously found that stimulation of the cAMP-dependent signaling pathway also triggers differentiation of cerebral cortical precursor cells into astrocytes, providing an additional mechanism to promote astrocyte differentiation. In this study, we show that pituitary adenylate cyclase-activating polypeptide (PACAP), but not the related vasoactive intestinal peptide, induces astrocyte differentiation of cortical precursor cells, even after a transient exposure. Cortical precursors were found to express predominantly the short isoform of the PACAP-specific PAC1 receptor, which couples to adenylate cyclase. Consistent with this notion, we determined that exposure of cortical precursors to PACAP resulted in a dose-dependent increase in cAMP production. Pretreatment of cells with the cAMP antagonist Rp-cAMPS prevented astrocyte differentiation. Thus, PACAP acts as an extracellular signal to trigger cortical precursor cell differentiation into astrocytes via stimulation of intracellular cAMP production. C1 Univ Autonoma Madrid, Consejo Super Invest Cient, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA USA. RP Vallejo, M (reprint author), Univ Autonoma Madrid, Consejo Super Invest Cient, Inst Invest Biomed Alberto Sols, Calle Arturo Duperier 4, Madrid 28029, Spain. OI Vallejo Fernandez de la Reguera, Inmaculada/0000-0002-7047-9219 FU NIDDK NIH HHS [DK-49670] NR 61 TC 37 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD DEC PY 2002 VL 21 IS 4 BP 671 EP 683 DI 10.1006/mcne.2002.1189 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 628ZQ UT WOS:000180026300013 PM 12504599 ER PT J AU Tsujikawa, K Ichijo, T Moriyama, K Tadotsu, N Sakamoto, K Sakane, N Fukada, S Furukawa, T Saito, H Yamamoto, H AF Tsujikawa, K Ichijo, T Moriyama, K Tadotsu, N Sakamoto, K Sakane, N Fukada, S Furukawa, T Saito, H Yamamoto, H TI Regulation of Lck and Fyn tyrosine kinase activities by transmembrane protein tyrosine phosphatase leukocyte common antigen-related molecule SO MOLECULAR CANCER RESEARCH LA English DT Article ID HIPPOCAMPAL CHOLINERGIC INNERVATION; RECEPTOR-LIKE PROTEIN; T-CELL DEVELOPMENT; THYMOCYTE DEVELOPMENT; INSULIN-RECEPTOR; MICE LACKING; PHOSPHOTYROSINE PHOSPHATASE; LAR; EXPRESSION; CD45 AB Leukocyte common antigen-related molecule (LAR) is a receptor-like protein tyrosine phosphatase (PTPase) with two PTPase domains. In the present study, we detected the expression of LAR in the brain, kidney, and thymus of mice using anti-LAR PTPase domain subunit monoclonal antibody (mAb) YU1. In the thymus, LAR was expressed on CD4(-)CD8(-) and CD4(-)CD8(low) thymocytes. The development of thymocytes in CD45 knockout mice is blocked partially in the maturation of CD4(-)CD8(-) to CD4(+)CD8(+). We postulated that LAR regulates Lck and Fyn in the immature thymocytes. Transfection of wild-type LAR activated extracellular signal-regulated kinase signal transduction pathway in CD45-deficient Jurkat cells stimulated with anti-CD3 mAb. LAR mutants, with Cys to Ser mutation in the catalytic center of PTPase D1, bound to tyrosine-phosphorylated Lck and Fyn, and LAR PTPase domain 2 was tyrosine phosphorylated by Fyn tyrosine kinase. The phosphorylated LAR was associated with Fyn Src homology 2 domain. Moreover, LAR dephosphorylated phosphorylated tyrosine residues in both the COOH terminus and kinase domain of Fyn in vitro. Our results indicate that Lck and Fyn would be substrates of LAR in immature thymocytes and that each LAR PTPase domain plays distinct functional roles in phosphorylation and dephosphorylation. C1 Osaka Univ, Grad Sch Pharmaceut Sci, Dept Immunol, Suita, Osaka 5650871, Japan. Kagoshima Univ, Inst Canc Res, Dept Canc Chemotherapy, Kagoshima, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Tsujikawa, K (reprint author), Osaka Univ, Grad Sch Pharmaceut Sci, Dept Immunol, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan. EM tujikawa@phs.osaka-u.ac.jp OI Fukada, So-ichiro/0000-0003-4051-5108 NR 50 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2002 VL 1 IS 2 BP 155 EP 163 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 659JA UT WOS:000181772500008 PM 12496362 ER PT J AU Anderson, KC Dalton, WS AF Anderson, KC Dalton, WS TI Synopsis of a research roundtable presented on cell signaling in myeloma: Regulation of growth and apoptosis - Opportunities for new drug discovery SO MOLECULAR CANCER THERAPEUTICS LA English DT Review ID MULTIPLE-MYELOMA; CONFERS RESISTANCE; IN-VIVO; THERAPY; LINES; INHIBITORS; MECHANISM; KINASES; DISEASE; BIOLOGY AB A wide variety of alterations affect important cell-signaling pathways involved in growth, survival, and migration of myeloma cells. Several of these pathways have been identified, and a number of potential anticancer agents are in development to block specific cell signaling proteins. The fifth experts' roundtable in multiple myeloma was convened in May 2001 to focus on this important issue. The roundtable brought together myeloma experts, researchers involved in cell signaling, industry scientists, and investigators studying other hematologic malignancies, with the single purpose of challenging current thought and increasing the collective knowledge in the evolving field of cell signaling and multiple myeloma. The session was cochaired by Dr. William S. Dalton of the H. Lee Moffitt Cancer Center and Dr. Kenneth C. Anderson of the Dana-Farber Cancer Institute. Sponsored by the Dana-Farber Cancer Institute, the roundtable was funded by the Multiple Myelonna Research Foundation and McCarty Cancer Foundation of Canada. C1 Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA. Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. RP Dalton, WS (reprint author), Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA. EM dalton@moffitt.usf.edu NR 28 TC 6 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2002 VL 1 IS 14 BP 1361 EP 1365 PG 5 WC Oncology SC Oncology GA 630CU UT WOS:000180090600015 PM 12516971 ER PT J AU Powell, SN Willers, H Xia, F AF Powell, SN Willers, H Xia, F TI BRCA2 keeps Rad51 in line: High-fidelity homologous recombination prevents breast and ovarian cancer? SO MOLECULAR CELL LA English DT Article ID REPAIR AB The mechanistic link between the BRCA2 protein, homologous recombination, and genomic instability has become clearer as a result of recent work describing the structures of different BRCA2 domains bound to Rad51 and to single-stranded DNA. C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA. RP Powell, SN (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Xia, Fen/G-3708-2013 NR 6 TC 31 Z9 34 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2002 VL 10 IS 6 BP 1262 EP 1263 DI 10.1016/S1097-2765(02)00789-X PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628BE UT WOS:000179971300005 PM 12504001 ER PT J AU Rooney, S Sekiguchi, J Zhu, CM Cheng, HL Manis, J Whitlow, S DeVido, J Foy, D Chaudhuri, J Lombard, D Alt, FW AF Rooney, S Sekiguchi, J Zhu, CM Cheng, HL Manis, J Whitlow, S DeVido, J Foy, D Chaudhuri, J Lombard, D Alt, FW TI Leaky Scid phenotype associated with defective V(D)J coding end processing in Artemis-deficient mice SO MOLECULAR CELL LA English DT Article ID DEPENDENT PROTEIN-KINASE; DNA-REPAIR PROTEIN; SEVERE COMBINED IMMUNODEFICIENCY; COMBINED IMMUNE-DEFICIENCY; RECOMBINATION IN-VIVO; CELL RECEPTOR-GAMMA; CATALYTIC SUBUNIT; GENE REARRANGEMENTS; NONSENSE MUTATION; GENOMIC STABILITY AB Radiosensitive severe combined immune deficiency in humans results from mutations in Artemis, a protein which, when coupled with DNA-dependent protein kinase catalytic subunit (DNA-PKcs), possesses DNA hairpin-opening activity in vitro. Here, we report that Artemis-deficient mice have an overall phenotype similar to that of DNA-PKcs-deficient mice-including severe combined immunodeficiency associated with defects in opening and joining V(D)J coding hairpin ends and increased cellular ionizing radiation sensitivity. While these findings strongly support the notion that Artemis functions with DNA-PKcs in a subset of NHEJ functions, differences between Artemis- and DNA-PKcs-deficient phenotypes, most notably decreased fidelity of V(D)J signal sequence joining in DNA-PKcs-deficient but not Artemis-deficient fibroblasts, suggest additional functions for DNA-PKcs. Finally, Artemis deficiency leads to chromosomal instability in fibroblasts, demonstrating that Artemis functions as a genomic caretaker. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NCI NIH HHS [CA92615]; NIAID NIH HHS [AI35714] NR 49 TC 176 Z9 181 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2002 VL 10 IS 6 BP 1379 EP 1390 DI 10.1016/S1097-2765(02)00755-4 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628BE UT WOS:000179971300017 PM 12504013 ER PT J AU Harker, N Naito, T Cortes, M Hostert, A Hirschberg, S Tolaini, M Roderick, K Georgopoulos, K Kioussis, D AF Harker, N Naito, T Cortes, M Hostert, A Hirschberg, S Tolaini, M Roderick, K Georgopoulos, K Kioussis, D TI The CD8 alpha gene locus is regulated by the Ikaros family of proteins SO MOLECULAR CELL LA English DT Article ID POSITION-EFFECT VARIEGATION; TRANSGENIC MICE; T-CELLS; TRANSCRIPTION FACTOR; DNA-BINDING; EXPRESSION; HETEROCHROMATIN; THYMOCYTES; CD8; LYT-2 AB Ikaros family members are important regulatory factors in lymphocyte development. Here we show that Ikaros may play an important role in CD4 versus CD8 lineage commitment decisions by demonstrating: (1) that it binds to regulatory elements in the endogenous CD8alpha locus in vivo using thymocyte chromatin immunoprecipitations, (2) that Ikaros suppresses position effect variegation of transgenes driven by CD8 regulatory elements, and (3) that mice with reduced levels of Ikaros and Aiolos show an apparent increase in CD4 populations with immature phenotype, i.e., cells that failed to activate the CD8alpha gene locus. We propose that Ikaros family members function as activators of the CD8alpha. gene locus and that their associated activities are critical for appropriate chromatin remodeling transitions during thymocyte differentiation and lineage commitment. C1 Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Kioussis, D (reprint author), Natl Inst Med Res, MRC, Div Mol Immunol, Mill Hill, London NW7 1AA, England. FU NIAID NIH HHS [R01-AI380342] NR 36 TC 106 Z9 110 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2002 VL 10 IS 6 BP 1403 EP 1415 DI 10.1016/S1097-2765(02)00711-6 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628BE UT WOS:000179971300019 PM 12504015 ER PT J AU Brodsky, AS Silver, PA AF Brodsky, AS Silver, PA TI A microbead-based system for identifying and characterizing RNA-protein interactions by flow cytometry SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID OLIGONUCLEOTIDE ARRAYS; MESSENGER-RNAS; IDENTIFICATION; HYBRIDIZATION; LIBRARIES; YEAST; POLYMORPHISMS; DENSITY; SITES; DNA AB We present a high throughput, versatile approach to identify RNA-protein interactions and to determine nucleotides important for specific protein binding. In this approach, oligonucleotides are coupled to microbeads and hybridized to RNA-protein complexes. The presence or absence of RNA and/or protein fluorescence indicates the formation of an oligo-RNA-protein complex on each bead. The observed fluorescence is specific for both the hybridization and the RNA-protein interaction. We find that the method can discriminate noncomplementary and mismatch sequences. The observed fluorescence reflects the affinity and specificity of the RNA-protein interaction. In addition, the fluorescence patterns footprint the protein recognition site to determine nucleotides important for protein binding. The system was developed with the human protein U1A binding to RNAs derived from U1 snRNA but can also detect RNA-protein interactions in total RNA backgrounds. We propose that this strategy, in combination with emerging coded bead systems, can identify RNAs and RNA sequences important for interacting with RNA-binding proteins on genomic scales. C1 Dana Farber Canc Inst, SM 922, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Brodsky, AS (reprint author), Dana Farber Canc Inst, SM 922, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM alex_brodsky@dfci.harvard.edu NR 21 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD DEC PY 2002 VL 1 IS 12 BP 922 EP 929 DI 10.1074/mcp.T200010-MCP200 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 721JV UT WOS:000185314000002 PM 12543929 ER PT J AU Raychowdhury, R Schafer, G Fleming, J Rosewicz, S Wiedenmann, B Wang, TC Hocker, M AF Raychowdhury, R Schafer, G Fleming, J Rosewicz, S Wiedenmann, B Wang, TC Hocker, M TI Interaction of early growth response protein 1 (Egr-1), specificity protein 1 (Sp1), and cyclic adenosine 3 ' 5 '-monophosphate response element binding protein (CREB) at a proximal response element is critical for gastrin-dependent activation of the chromogranin A promoter SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; A GENE; REGULATORY ELEMENT; EPITHELIAL-CELLS; RAT STOMACH; EXPRESSION; FAMILY; REPRESSION; SECRETION; PEPTIDES AB Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation. Gastrin elevated cellular and nuclear Egr-1 levels in a time-dependent manner and also increased Egr-1 binding to the CgA -92/-73 region. Disruption of this site reduced gastrin responsiveness without influencing basal promoter activity, while loss of Sp1 and/or CREB binding sites diminished basal and gastrin-stimulated CgA promoter activity. Ectopic Egr-1 overexpression potently stimulated the CgA promoter, whereas coexpression of Egr-1 with Sp1 and/or CREB resulted in additive effects. Functional analysis of Sp1-, Egr-1-, or CREB-specific promoter mutations in transfection studies confirmed the tripartite organization of the CgA -92/ -62 element. Signaling studies revealed that MAPK kinase 1 (MEK1)/ERK1/2 cascades are critical for gastrin-dependent Egr-1 protein accumulation as well as Egr-1 binding to the CgA promoter. Our studies for the first time identify Egr-1 as a nuclear target of gastrin and show that functional interplay of Egr-1, Sp1, and CREB is indispensable for gastrin-dependent CgA transactivation in gastric epithelial cells. C1 Humbolt Univ Berlin, Charite, Med Klin Schwerpunkt Gastorenterol Hepatol Endokr, D-13353 Berlin, Germany. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hocker, M (reprint author), Humbolt Univ Berlin, Charite, Med Klin Schwerpunkt Gastorenterol Hepatol Endokr, Augustenburg Pl 1,Campus Virchow Klinikum, D-13353 Berlin, Germany. FU NIDDK NIH HHS [R01 DK 48077] NR 46 TC 48 Z9 49 U1 0 U2 3 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 DEC PY 2002 VL 16 IS 12 BP 2802 EP 2818 DI 10.1210/me.2001-0292 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623EE UT WOS:000179689700012 PM 12456801 ER PT J AU Nakanishi, K Taniguchi, T Ranganathan, V New, HV Moreau, LA Stotsky, M Mathew, CG Kastan, MB Weaver, DT D'Andrea, AD AF Nakanishi, K Taniguchi, T Ranganathan, V New, HV Moreau, LA Stotsky, M Mathew, CG Kastan, MB Weaver, DT D'Andrea, AD TI Interaction of FANCD2 and NBS1 in the DNA damage response SO NATURE CELL BIOLOGY LA English DT Article ID NIJMEGEN BREAKAGE SYNDROME; FANCONI-ANEMIA PROTEINS; DOUBLE-STRAND BREAKS; ATAXIA-TELANGIECTASIA; S-PHASE; NUCLEAR-LOCALIZATION; COMPLEX; REPAIR; BRCA1; ATM AB Fanconi anaemia (FA) and Nijmegen breakage syndrome (NBS) are autosomal recessive chromosome instability syndromes with distinct clinical phenotypes. Cells from individuals affected with FA are hypersensitive to mitomycin C (MMC), and cells from those with NBS are hypersensitive to ionizing radiation. Here we report that both NBS cell lines and individuals with NBS are hypersensitive to MMC, indicating that there may be functional linkage between FA and NBS. In wild-type cells, MMC activates the colocalization of the FA subtype D2 protein (FANCD2) and NBS1 protein in subnuclear foci. Ionizing radiation activates the ataxia telangiectasia kinase (ATM)-dependent and NBS1-dependent phosphorylation of FANCD2, resulting in an S-phase checkpoint. NBS1 and FANCD2 therefore cooperate in two distinct cellular functions, one involved in the DNA crosslink response and one involved in the S-phase checkpoint response. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Great Ormond St Hosp Sick Children, Dept Haematol, London WC1N 3JH, England. Guys Kings & St Thomas Sch Med, Div Med & Mol Genet, London SE1 9RT, England. St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. RP Nakanishi, K (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Mathew, Christopher/G-3434-2015 OI Mathew, Christopher/0000-0003-4178-1838 NR 38 TC 179 Z9 185 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2002 VL 4 IS 12 BP 913 EP 920 DI 10.1038/ncb879 PG 8 WC Cell Biology SC Cell Biology GA 621CW UT WOS:000179571800010 PM 12447395 ER PT J AU Leader, B Lim, H Carabatsos, MJ Harrington, A Ecsedy, J Pellman, D Maas, R Leder, P AF Leader, B Lim, H Carabatsos, MJ Harrington, A Ecsedy, J Pellman, D Maas, R Leder, P TI Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes SO NATURE CELL BIOLOGY LA English DT Article ID MITOTIC SPINDLE; DROSOPHILA; GENE; MATURATION; CAPPUCCINO; POLARITY; HOMOLOG; MICE; EGGS; REORGANIZATION AB Successful reproduction in mammals requires a competent egg, which is formed during meiosis through two assymetrical cell divisions. Here, we show that a recently identified formin homology (FH) gene, formin-2 (Fmn2), is a maternal-effect gene that is expressed in oocytes and is required for progression through metaphase of meiosis I. Fmn2(-/-) oocytes cannot correctly position the metaphase spindle during meiosis I and form the first polar body. We demonstrate that Fmn2 is required for microtubule-independent chromatin positioning during metaphase I. Fertilization of Fmn2(-/-) oocytes results in polyploid embryo formation, recurrent pregnancy loss and sub-fertility in Fmn2(-/-) females. Injection of Fmn2 mRNA into Fmn2-deficient oocytes rescues the metaphase I block. Given that errors in meiotic maturation result in severe birth defects and are the most common cause of chromosomal aneuploidy and pregnancy loss in humans, studies of Fmn2 may provide a better understanding of infertility and birth defects. C1 Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Genet, Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. RP Leader, B (reprint author), Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, 200 Longwood Ave, Boston, MA 02115 USA. RI Lim, Hyunjung/D-5343-2011 OI Lim, Hyunjung/0000-0003-2191-666X NR 44 TC 194 Z9 203 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2002 VL 4 IS 12 BP 921 EP 928 DI 10.1038/ncb880 PG 8 WC Cell Biology SC Cell Biology GA 621CW UT WOS:000179571800011 PM 12447394 ER PT J AU Prokunina, L Castillejo-Lopez, C Oberg, F Gunnarsson, I Berg, L Magnusson, V Brookes, AJ Tentler, D Kristjansdottir, H Grondal, G Bolstad, AI Svenungsson, E Lundberg, I Sturfelt, G Jonssen, A Truedsson, L Lima, G Alcocer-Varela, J Jonsson, R Gyllensten, UB Harley, JB Alarcon-Segovia, D Steinsson, K Alarcon-Riquelme, ME AF Prokunina, L Castillejo-Lopez, C Oberg, F Gunnarsson, I Berg, L Magnusson, V Brookes, AJ Tentler, D Kristjansdottir, H Grondal, G Bolstad, AI Svenungsson, E Lundberg, I Sturfelt, G Jonssen, A Truedsson, L Lima, G Alcocer-Varela, J Jonsson, R Gyllensten, UB Harley, JB Alarcon-Segovia, D Steinsson, K Alarcon-Riquelme, ME TI A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans SO NATURE GENETICS LA English DT Article ID ALLELE-SPECIFIC HYBRIDIZATION; SIB-PAIR FAMILIES; HUMAN PD-1 GENE; AUTOIMMUNE-DISEASES; CROHNS-DISEASE; T-LYMPHOCYTES; EXPRESSION; IMMUNORECEPTOR; TOLERANCE; PEDIGREES AB Systemic lupus erythematosus (SLE, OMIM 152700) is a complex autoimmune disease that affects 0.05% of the Western population, predominantly women(1-4). A number of susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes and mutations is yet to be identified(5-9). We previously reported a susceptibility locus (SLEB2) for Nordic multi-case families(9,10). Within this locus, the programmed cell death 1 gene (PDCD1, also called PD-1) was considered the strongest candidate for association with the disease(11-14). Here, we analyzed 2,510 individuals, including members of five independent sets of families as well as unrelated individuals affected with SLE, for single-nucleotide polymorphisms (SNPs) that we identified in PDCD1. We show that one intronic SNP in PDCD1 is associated with development of SLE in Europeans (found in 12% of affected individuals versus 5% of controls; P=0.00001, r.r. (relative risk)=2.6) and Mexicans (found in 7% of affected individuals versus 2% of controls; P=0.0009, r.r.=3.5). The associated allele of this SNP alters a binding site for the runt-related transcription factor 1 (RUNX1, also called AML1) located in an intronic enhancer, suggesting a mechanism through which it can contribute to the development of SLE in humans. C1 Univ Uppsala, Rudbeck Labs, Inst Genet & Pathol, Med Genet Sect, S-75185 Uppsala, Sweden. Everygene AB, Uppsala, Sweden. Univ Uppsala, Rudbeck Labs, Inst Genet & Pathol, Sect Pathol, S-75185 Uppsala, Sweden. Univ Uppsala, Evolut Biol Ctr, Dept Comparat Physiol, S-75185 Uppsala, Sweden. Karolinska Inst, Rheumatol Unit, Stockholm, Sweden. Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden. Karolinska Inst, Ctr Genom & Bioinformat, Stockholm, Sweden. Labdpitalinn, Dept Rheumatol, Reykjavik, Iceland. Labdpitalinn, Ctr Rheumatol Res, Reykjavik, Iceland. Univ Bergen, Broegelmann Res Lab, Bergen, Norway. Haukeland Univ Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. Univ Lund Hosp, Dept Clin Immunol, S-22185 Lund, Sweden. Univ Lund Hosp, Dept Rheumatol, S-22185 Lund, Sweden. Inst Nacl Ciencias Med & Nutr Salvador Zubirdan, Dept Immunol & Rheumatol, Mexico City, DF, Mexico. Univ Oklahoma, Dept Med, Arthrit & Immunol Program, Oklahoma Med Res Fdn, Oklahoma City, OK USA. US Dept Vet Affairs, Oklahoma City, OK USA. RP Alarcon-Riquelme, ME (reprint author), Univ Uppsala, Rudbeck Labs, Inst Genet & Pathol, Med Genet Sect, Dag Hammarsjolds Vag 20, S-75185 Uppsala, Sweden. RI Hoiom, Veronica/F-4153-2012; OI Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Svenungsson, Elisabet/0000-0003-3396-3244; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154 NR 29 TC 467 Z9 486 U1 3 U2 21 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2002 VL 32 IS 4 BP 666 EP 669 DI 10.1038/ng1020 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 621MH UT WOS:000179593000022 PM 12402038 ER PT J AU Bardeesy, N DePinho, RA AF Bardeesy, N DePinho, RA TI Pancreatic cancer biology and genetics SO NATURE REVIEWS CANCER LA English DT Review ID EPIDERMAL GROWTH-FACTOR; NONPOLYPOSIS COLORECTAL-CANCER; PEUTZ-JEGHERS-SYNDROME; TUMOR-SUPPRESSOR GENE; K-RAS; INTRAEPITHELIAL NEOPLASIA; TELOMERE DYSFUNCTION; FACTOR RECEPTOR; FACTOR-ALPHA; IN-VITRO AB Pancreatic ductal adenocarcinoma is an aggressive and devastating disease, which is characterized by invasiveness, rapid progression and profound resistance to treatment. Advances in pathological classification and cancer genetics have improved our descriptive understanding of this disease; however, important aspects of pancreatic cancer biology remain poorly understood. What is the pathogenic role of specific gene mutations? What is the cell of origin? And how does the stroma contribute to tumorigenesis? A better understanding of pancreatic cancer biology should lead the way to more effective treatments. C1 Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 151 TC 659 Z9 682 U1 14 U2 104 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2002 VL 2 IS 12 BP 897 EP 909 DI 10.1038/nrc949 PG 13 WC Oncology SC Oncology GA 636HJ UT WOS:000180448300010 PM 12459728 ER PT J AU Hideshima, T Anderson, KC AF Hideshima, T Anderson, KC TI Molecular mechanisms of novel therapeutic approaches for multiple myeloma SO NATURE REVIEWS CANCER LA English DT Review ID HIGH-DOSE THERAPY; ENDOTHELIAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; ALLOGENEIC BONE-MARROW; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; DEXAMETHASONE-INDUCED APOPTOSIS; PROTEASOME INHIBITOR PS-341; STEM-CELL TRANSPLANTATION; OVERCOMES DRUG-RESISTANCE AB Multiple myeloma remains largely incurable despite conventional and high-dose therapies, and so novel biologically based treatment approaches are urgently required. Recent studies have characterized the molecular mechanisms by which multiple myeloma cell-host bone-marrow interactions regulate tumour cell growth, survival and migration in the bone-marrow microenvironment. These studies have not only enhanced our understanding of disease pathogenesis, but have also provided the framework for a new treatment model that targets the multiple myeloma cell in its bone-marrow microenvironment to overcome drug resistance and improve patient outcome. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 140 TC 304 Z9 311 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2002 VL 2 IS 12 BP 927 EP 937 DI 10.1038/nrc952 PG 11 WC Oncology SC Oncology GA 636HJ UT WOS:000180448300013 PM 12459731 ER PT J AU Chiocca, EA AF Chiocca, EA TI Oncolytic viruses SO NATURE REVIEWS CANCER LA English DT Review ID HERPES-SIMPLEX VIRUS; DEPENDENT PROTEIN-KINASE; SQUAMOUS-CELL CARCINOMA; CYTOKINE GENE-TRANSFER; RAS SIGNALING PATHWAY; LONG-TERM SURVIVAL; PHASE-I TRIAL; REPLICATION-COMPETENT; BRAIN-TUMORS; RIBONUCLEOTIDE REDUCTASE AB Although the cytotoxic effects of viruses are usually viewed in terms of pathogenicity, it is possible to harness this activity for therapeutic purposes. Viral genomes are highly versatile, and can be modified to direct their cytotoxicity towards cancer cells. These viruses are known as oncolytic viruses. How are viruses engineered to become tumour specific, and can they be used to safely treat cancer in humans?. C1 Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurol Serv, Charlestown, MA 02129 USA. RP Chiocca, EA (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurol Serv, East Bldg,13th St,Bldg 149, Charlestown, MA 02129 USA. NR 158 TC 191 Z9 199 U1 6 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2002 VL 2 IS 12 BP 938 EP 950 DI 10.1038/nrc948 PG 13 WC Oncology SC Oncology GA 636HJ UT WOS:000180448300014 PM 12459732 ER PT J AU Jara, A Chacon, C Felsenfeld, AJ AF Jara, A Chacon, C Felsenfeld, AJ TI Hyperphosphatemia modestly retards parathyroid hormone suppression during calcitriol-induced hypercalcemia in normal and azotemic rats SO NEPHRON LA English DT Article DE calcitriol; hyperparathyroidism; parathyroid hormone; phosphate; renal failure ID VITAMIN-D METABOLITES; TISSUE IN-VITRO; SECONDARY HYPERPARATHYROIDISM; GENE-EXPRESSION; SENSING RECEPTOR; CALCIUM RECEPTOR; PTH SECRETION; RENAL-FAILURE; UREMIC RATS; PHOSPHATE AB Background/Aims: In in vitro studies, a high phosphate concentration has been shown to directly stimulate parathyroid hormone (PTH) secretion in a normal calcium concentration and to reduce PTH suppression in a high calcium concentration. In hemodialysis patients during dialysis-induced hypercalcemia, the effect of hyperphosphatemia on PTH secretion was less than in vitro studies. Our goal was to determine whether hyperphosphatemia retards PTH suppression during calcitriol-induced hypercalcemia in azotemic rats with hyperparathyroidism. Methods: Rats underwent a two-stage 5/6 nephrectomy or sham operations. After surgery, rats received a high phosphate diet (P 1.2%, Ca 0.6%) for 4 weeks to induce hyperparathyroidism and then were placed on a normal diet (P 0.6%, Ca 0.6%) for two additional weeks to normalize serum calcium values in azotemic rats. At week 7, rats were divided into five groups and before sacrifice received at 24-hour intervals, three doses of calcitriol (CTR) or its vehicle. The five groups and dietary phosphate content were: group 1 - normal renal function (NRF) + 0.6% P + vehicle; group 2 - NRF + 0.6% P + CTR; group 3 - renal failure (RF) + 0.6% P + vehicle; group 4 RF + 1.2% P + CTR; and group 5 - RF + 0.6% P + CTR. Results: In the two CTR-treated groups with marked hypercalcemia (groups 2 and 5), 15.52 +/- 0.26 and 15.12 +/- 0.13 mg/dl, respectively, stepwise regression showed that hyperphosphatemia retarded PTH suppression. When the two azotemic groups treated with CTR (groups 4 and 5) were combined to expand the range of serum calcium values, stepwise regression showed that hypercalcemia suppressed and hyperphosphatemia modestly retarded PTH suppression. Similarly, in groups 4 and 5 combined, correlations were present between PTH and both serum calcium (r = -0.70, p < 0.001) and serum phosphate (r = 0.64, p = 0.001). Conclusions: Hypercalcemia and high doses of calcitriol markedly reduced PTH secretion in azotemic rats despite severe hyperphosphatemia. Even though hyperphosphatemia did retard PTH suppression during hypercalcemia, its effect was small. Copyright (C) 2002 S. Karger AG, Basel. C1 Pontificia Univ Catolica Chile, Dept Nephrol, Santiago, Chile. W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Jara, A (reprint author), Pontificia Univ Catolica Chile, Dept Nephrol, Marcoleta 345, Santiago, Chile. NR 35 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD DEC PY 2002 VL 92 IS 4 BP 883 EP 888 DI 10.1159/000065454 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 611FZ UT WOS:000179006900019 PM 12399635 ER PT J AU Andreassen, OA Dedeoglu, A Stanojevic, V Hughes, DB Browne, SE Leech, CA Ferrante, RJ Habener, JF Beal, MF Thomas, MK AF Andreassen, OA Dedeoglu, A Stanojevic, V Hughes, DB Browne, SE Leech, CA Ferrante, RJ Habener, JF Beal, MF Thomas, MK TI Huntington's disease of the endocrine pancreas: Insulin deficiency and diabetes mellitus due to impaired insulin gene expression SO NEUROBIOLOGY OF DISEASE LA English DT Article ID HEDGEHOG SIGNALING REGULATION; HOMEODOMAIN PROTEIN IDX-1; CREB-BINDING PROTEIN; EXPANDED CAG REPEAT; TRANSGENIC MICE; ISLET CELLS; FACTOR-I; NEURODEGENERATIVE DISEASES; TRANSCRIPTIONAL ACTIVATION; MEDIATED TRANSCRIPTION AB In a transgenic mouse model of the neurodegenerative disorder Huntington's disease (HD), age-dependent neurologic defects are accompanied by progressive alterations in glucose tolerance that culminate in the development of diabetes mellitus and insulin deficiency. Pancreatic islets from HD transgenic mice express reduced levels of the pancreatic islet hormones insulin, somatostatin, and glucagon and exhibit intrinsic defects in insulin production. Intranuclear inclusions accumulate with aging in transgenic pancreatic islets, concomitant with the decline in glucose tolerance. HD transgenic mice develop an age-dependent reduction of insulin mRNA expression and diminished expression of key regulators of insulin gene transcription, including the pancreatic homeoprotein PDX-1, E2A proteins, and the coactivators CBP and p300. Disrupted expression of a subset of transcription factors in pancreatic beta cells by a polyglutamine expansion tract in the huntingtin protein selectively impairs insulin gene expression to result in insulin deficiency and diabetes. Selective dysregulation of gene expression in triplet repeat disorders provides a mechanism for pleiotropic cellular dysfunction that restricts the toxicity of ubiquitously expressed proteins to highly specialized subpopulations of cells. (C) 2003 Elsevier Science (USA). C1 Massachusetts Gen Hosp, Lab Mol Endocrinol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurochem Lab, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Cornell Univ, New York Hosp, Med Ctr, Dept Neurol, New York, NY 10021 USA. RP Thomas, MK (reprint author), Massachusetts Gen Hosp, Lab Mol Endocrinol, Wellman 340,50 Blossom St, Boston, MA 02114 USA. OI Dedeoglu, Alpaslan/0000-0003-1156-0874; Andreassen, Ole A./0000-0002-4461-3568 FU NIA NIH HHS [AG12292]; NIDDK NIH HHS [DK55365, DK02476]; NINDS NIH HHS [NS31579] NR 85 TC 73 Z9 75 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2002 VL 11 IS 3 BP 410 EP 424 DI 10.1006/nbdi.2002.0562 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 643NC UT WOS:000180866500005 PM 12586550 ER PT J AU Pekary, AE Senanayake, S Sattin, A AF Pekary, AE Senanayake, S Sattin, A TI Cocaine regulates TRH-related peptides in rat brain SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE limbic system; cocaine; TRH-like peptides; HPLC; radioimmunoassay ID THYROTROPIN-RELEASING-HORMONE; MONKEY PREFRONTAL CORTEX; SEIZURES INCREASE LEVELS; CENTRAL-NERVOUS-SYSTEM; CEREBRAL-BLOOD-FLOW; NUCLEUS-ACCUMBENS; MICE LACKING; NORMAL WOMEN; SUBSTANCE-P; DOPAMINE AB Cocaine administration has previously been reported to alter the levels of prepro-TRH mRNA and TRH (pGlu-His-Pro-NH2) in the limbic system of rats (J. Neurochem. 60 (1993) 115 1). We have now demonstrated that a previously unrecognized family of TRH-like peptides is involved in the actions of cocaine. We treated young adult male Sprague-Dawley rats (five per group, 250 g body weight at sacrifice) for 2 weeks with either twice daily injections of saline (control group), twice daily injections of 15 mg/kg cocaine until sacrifice (chronic group), single injection of 15 mg/kg cocaine 2 h prior to sacrifice (acute group) or chronic cocaine injections replaced by saline injections 72 h prior to sacrifice (withdrawal group (WD)). Twelve different brain regions were dissected and immunoreactivity for TRH (TRH-IR), EEP (pGlu-Glu-Pro-NH2; EEP-IR) and related peptides were measured by radioimmunoassay (RIA). High pressure liquid chromatography (HPLC) revealed that in many brain regions EEP-IR and TRH-IR consisted of a mixture of TRH, and other TRH-like peptides including EEP, pGlu-Val-Pro-NH2) (Val(2)-TRH), pGlu-Tyr-Pro-NH2 (Tyr(2)-TRH), pGlu-Leu-Pro-NH2 (Leu(2)-TRH), and pGlu-Phe-Pro-NH2 (Phe(2)-TRH). Following i.p. injection, these TRH-like peptides readily crossed the blood-brain barrier but cleared very slowly from brain tissues. Acute cocaine produced a 4.1-fold increase in Val(2)-TRH level in medulla while Val(2)-TRH and Tyr(2)-TRH, increased 6.2- and 2.9-fold, respectively in pyriform cortex PYR. TRH and Leu(2)-TRH, decreased 47 and 93%, respectively in the nucleus accumbens (AM) while other EEP-IR peaks decreased 50-100% consistent with the significant decrease in total EEP-IR in the AMs following acute cocaine treatment. Because 2 h is too short a time to alter levels of neuropeptides via changes in the rate of biosynthesis, the acute cocaine-induced elevation or reduction in TRH and related peptides is most likely due to suppression or stimulation, respectively, of the corresponding peptide secretion rate. Because TRH and TRH-like peptides have antidepressant, analeptic and euphorigenic properties, we conclude that these endogenous substances are potential mediators of both the cocaine "high" and withdrawal symptoms. Published by Elsevier Science Ltd. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Biobehav Sci & Brain Res Inst, Los Angeles, CA 90073 USA. RP Pekary, AE (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, Bldg 114,Room 229,111301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM epekary@ucla.edu NR 75 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 EI 1872-9754 J9 NEUROCHEM INT JI Neurochem. Int. PD DEC PY 2002 VL 41 IS 6 BP 415 EP 428 AR PII S0197-0186(02)00022-0 PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 598VR UT WOS:000178297600006 ER PT J AU Moore, KA Baba, H Woolf, CJ AF Moore, KA Baba, H Woolf, CJ TI Gabapentin - Actions on adult superficial dorsal horn neurons SO NEUROPHARMACOLOGY LA English DT Article DE gabapentin; NMDA; synaptic transmission; spinal cord ID RAT SPINAL-CORD; SUBSTANTIA-GELATINOSA NEURONS; CURRENTS; SLICES; INFLAMMATION; INHIBITION; RESPONSES; RELEASE; ACID AB Despite identification of GABA(B) receptors with gb1a-gb2 composition and the alpha2delta calcium channel subunit as putative molecular targets for gabapentin (GBP), its cellular mechanism of action has remained elusive. Therefore, we have used an in vitro spinal cord slice preparation to study the effects of GBP on lamina 11 neurons. The frequency and amplitude of spontaneous EPSCs and IPSCs were unaffected by GBP, suggesting presynaptic neurotransmitter release is not regulated. Direct modulation of postsynaptic membrane excitability is also unlikely since the level of holding current required to maintain neurons at -70, 0 and +45 mV was unaffected by GBP. Effects on excitatory and inhibitory synaptic transmission were variable across the population. Primary afferent-evoked fast glutamatergic EPSCs were unaffected by GBP, while evoked NMDA receptor-mediated EPSCs and IPSCs were variably affected. In contrast, GBP enhanced responses to bath applied NMDA in 71% of neurons. Thus, in adult rat dorsal horn, synaptic and extrasynaptic NMDA receptors may be differentially regulated by GBP perhaps due to differences in subunit composition. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Moore, KA (reprint author), Univ Calif San Francisco, 513 Parnassus Ave, San Francisco, CA 94143 USA. FU NINDS NIH HHS [NS38253-01] NR 21 TC 36 Z9 36 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 2002 VL 43 IS 7 BP 1077 EP 1081 DI 10.1016/S0028-3908(02)00226-5 PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 639DY UT WOS:000180613400004 PM 12504913 ER PT J AU Schaechter, JD Kraft, E Hilliard, TS Dijkhuizen, RM Benner, T Finklestein, SP Rosen, BR Cramer, SC AF Schaechter, JD Kraft, E Hilliard, TS Dijkhuizen, RM Benner, T Finklestein, SP Rosen, BR Cramer, SC TI Motor recovery and cortical reorganization after constraint-induced movement therapy in stroke patients: A preliminary study SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE stroke; hemiparesis; rehabilitation; magnetic resonance imaging; motor cortex ID FUNCTIONAL MRI; CEREBRAL ACTIVATION; HEMIPARETIC STROKE; CORTEX ACTIVATION; FINGER MOVEMENTS; HUMAN BRAIN; INFARCTION; PLASTICITY; FORCE; FMRI AB Constraint-induced movement therapy (CIMT) is a physical rehabilitation regime that has been previously shown to improve motor function in chronic hemiparetic stroke patients. However the neural mechanisms supporting rehabilitation-induced motor recovery are poorly understood. The goal of this study was to assess motor conical reorganization after CIMT using functional magnetic resonance imaging (fMRI). In a repeated-measures design, 4 incompletely recovered chronic stroke patients treated with CIMT underwent motorfunction testing and fMRI. Five age-matched normal subjects were also imaged. A laterality index (LI) was determined from the fMRI data, reflecting the distribution of activation in motor cortices contralateral compared with ipsilateral to the moving hand. Pre-intervention fMRI showed a lower LI during affected band movement of stroke patients (LI = 0.23 +/- 0.07) compared to controls (LI unaffected patient band = 0.65 +/- 0.10; LI dominant normal hand = 0.65 +/- 0.11; LI nondominant normal band = 0.69 +/- 0.11; P < 0.05) due to trends toward increased ipsilateral motor conical activation. Motor function testing showed that patients made significant gains in functional use of the stroke-affected upper extremity (detected by the Motor Activity Log) and significant reductions in motor impairment (detected by the Fugl-Meyer Stroke Scale and the Wolf Motor Function Test) immediately after CIMT and these effects persisted at 6-month follow-up. The behavioral effects of CIMT were associated with a trend toward a reduced LI from pre-intervention to immediately post-intervention (LI = -0.01 +/- 0.06; P = 0.077) and 6 months post-intervention (LI = -0.03 +/- 0.15). Stroke-affected band movement was not accompanied by mirror movements during fMRI, and electromyographic measures of mirror recruitment under simulated fMRI conditions were not correlated with LI values. These data provide preliminary evidence that gains in motor Junction produced by CIMT in chronic stroke patients may be associated with a shift in laterality of motor conical activation toward the undamaged hemisphere. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Univ Ulm, Sch Med, D-89069 Ulm, Germany. Northeastern Univ, Dept Phys Therapy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. RP Schaechter, JD (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, 13th St,Bldg 149,Room 2301, Charlestown, MA 02129 USA. EM judith@nmr.mgh.harvard.edu RI Dijkhuizen, Richard/A-6506-2008 NR 51 TC 156 Z9 173 U1 2 U2 27 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD DEC PY 2002 VL 16 IS 4 BP 326 EP 338 DI 10.1177/0888439002239281 PG 13 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 845IJ UT WOS:000223235400003 PM 12462764 ER PT J AU Tarazi, FI Zhang, KH Baldessarini, RJ AF Tarazi, FI Zhang, KH Baldessarini, RJ TI Long-term effects of newer antipsychotic drugs on neuronal nitric oxide synthase in rat brain SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE autoradiography; frontal cortex; hippocampus; L-N-g-nitroarginine; olanzapine; quetiapine; risperidone ID REFLECT ABNORMALITIES; DIAPHORASE NEURONS; INHIBITION; BINDING AB Neuronal nitric oxide synthase (nNOS) catalyzes the synthesis of neuronal nitric oxide from L-arginine. Behavioral and neurochemical studies implicate neuronal nitric oxide in the pathophysiology of schizophrenia and in the actions of standard antipsychotic drugs. However, involvement of nNOS in the actions of newer antipsychotic drugs requires further investigation. Accordingly, density levels of nNOS, a marker for neuronal nitric oxide production, were examined in rat forebrain regions by computed autoradiography after repeated treatment (28 days) with three newer antipsychotic agents, olanzapine, risperidone, and quetiapine. No significant differences in nNOS levels were detected in representative cortical, limbic, and extrapyramidal brain regions of drug-treated vs vehicle-treated animals. The findings suggest that nNOS plays a minimal role in mediating the long-term actions of newer antipsychotic drugs. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-34006, MH-47370] NR 25 TC 27 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD DEC PY 2002 VL 7 IS 4 BP 297 EP 300 AR PII S1089-8603(02)00126-X DI 10.1016/S1089-8603(02)00126-X PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 625NH UT WOS:000179822200009 PM 12446179 ER PT J AU Frigoletto, FD Greene, MF AF Frigoletto, FD Greene, MF TI Is there a sea change ahead for obstetrics and gynecology? SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB A number of beneficial sociocultural reforms have occurred throughout our society, including a new work/family balance. This change, and a number of others, are challenging the dynamic balance within our specialty. We must advocate for appropriate social, political, and economic interventions that will realistically mesh with the health care needs of our nation, while preserving that which is best about the culture of American medicine. (Obstet Gynecol 2002;100:1342-3. (C) 2002 by The American College of Obstetricians and Gynecologists.) C1 Massachusetts Gen Hosp, Vincent Mem Obstet Gynecol Dept, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Frigoletto, FD (reprint author), 55 Fruit St,FND 416, Boston, MA 02114 USA. NR 6 TC 9 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2002 VL 100 IS 6 BP 1342 EP 1343 AR PII S0029-7844(02)02470-5 DI 10.1016/S0029-7844(02)02470-5 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 620GX UT WOS:000179526600028 PM 12468182 ER PT J AU Tanner, ACR Milgrom, PM Kent, R Mokeem, SA Page, RC Liao, SIA Riedy, CA Bruss, JB AF Tanner, ACR Milgrom, PM Kent, R Mokeem, SA Page, RC Liao, SIA Riedy, CA Bruss, JB TI Similarity of the oral microbiota of pre-school children with that of their caregivers in a population-based study SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Actinobacillus actinomycetemcomitans; Actinomyces; Bacteroides forsythus; caregiver microbiota; Porphyromonas gingivalis; pre-school children; Prevotella; Streptococcus mutans ID CARIES-ASSOCIATED MICROORGANISMS; ADULT PERIODONTITIS PATIENTS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS; SUBGINGIVAL MICROBIOTA; MUTANS STREPTOCOCCI; PREVOTELLA-INTERMEDIA; INITIAL ACQUISITION; YOUNG-CHILDREN; DENTAL-CARIES AB This study evaluated the similarity between the oral microbiota of young children and that of their adult caregivers. Oral samples from children (174 dentate and 18 pre-dentate) aged 6-36 months and their caregivers in Saipan were assayed using a DNA probe assay. Many species including Streptococcus mutans , Streptococcus sobrinus , Actinomyces species, Campylobacter rectus, Fusobacterium nucleatum, Prevotella intermedia , and Porphyromonas gingivalis were detected in dentate and pre-dentate children, whereas Bacteroides forsythus was detected only in dentate children. A higher percentage of children were positive for the detection of an individual species if the caregiver was also positive. There were significant relative risks of species detection between dentate children and their caregivers. By logistic regression, there were significant positive associations between species detection in caregiver and in child, but not between species detection and child age or maternal education level. In conclusion, dental pathogens were detected in young, including pre-dentate, children. The microbial profiles of children were strongly associated with the microbiota of their caregivers. C1 Forsyth Inst, Boston, MA 02115 USA. Univ Washington, Dept Dent Publ Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Dept Periodont, Seattle, WA 98195 USA. King Saud Univ, Riyadh, Saudi Arabia. Dept Periodont, Seattle, WA USA. RP Tanner, ACR (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. OI Milgrom, Peter/0000-0003-0784-9181 FU NIDCR NIH HHS [DE-07132, DE-09513, DE-14264, P01 DE-08555, P30 DE-09743, T35 DE-07150] NR 44 TC 27 Z9 28 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD DEC PY 2002 VL 17 IS 6 BP 379 EP 387 DI 10.1034/j.1399-302X.2002.170608.x PG 9 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 627CK UT WOS:000179911200008 PM 12485330 ER PT J AU Ayala, C Watkins, L Deschler, DG AF Ayala, C Watkins, L Deschler, DG TI Tension orbital pneumocele secondary to nasal obstruction from cocaine abuse: A case report SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Editorial Material ID CELLULITIS C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 2002 VL 127 IS 6 BP 572 EP 574 DI 10.1067/mhn.2002.129810 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 630BY UT WOS:000180088700013 PM 12501110 ER PT J AU Mao, JR AF Mao, JR TI Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy SO PAIN LA English DT Review ID ROSTRAL VENTROMEDIAL MEDULLA; PROTEIN-KINASE-C; MORPHINE-TOLERANCE; ANTINOCICEPTIVE TOLERANCE; HYPERALGESIA; MECHANISMS; NOCICEPTION; RECEPTORS; DYNORPHIN; FENTANYL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. FU NIDA NIH HHS [R01 DA 08835] NR 28 TC 237 Z9 250 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2002 VL 100 IS 3 BP 213 EP 217 AR PII S0304-3959(02)00422-0 DI 10.1016/S0304-3959(02)00422-0 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 624UQ UT WOS:000179780400002 PM 12467992 ER PT J AU Walker, RH Friedman, J Wiener, J Hobler, R Gwinn-Hardy, K Adam, A DeWolfe, J Gibbs, R Baker, M Farrer, M Hutton, M Hardy, J AF Walker, RH Friedman, J Wiener, J Hobler, R Gwinn-Hardy, K Adam, A DeWolfe, J Gibbs, R Baker, M Farrer, M Hutton, M Hardy, J TI A family with a tau P301L mutation presenting with parkinsonism SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE genetics; parkinsonism; progressive supranuclear palsy; dementia; tau ID FRONTOTEMPORAL DEMENTIA; EXTENDED HAPLOTYPE; GENE; DISEASE; CHROMOSOME-17; ASSOCIATION; POLYMORPHISMS; PHENOTYPE; MISSENSE; INSOMNIA AB We report a sib-pair with a tau P301L mutation. Unlike most previous cases with this mutation, parkinsonism, rather than dementing features were the predominant and presenting feature. We have also observed that the P301L mutation has occurred on the HI tau haplotype background. The haplotype background may influence the disease phenotype since in many previous Caucasian families with the P301L mutation, the haplotype background has been H2. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Mayo Clin Jacksonville, Labs Neurogenet, Dept Neurosci, Jacksonville, FL 32224 USA. Bronx Vet Adm Med Ctr, Dept Neurol, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Brown Univ, Sch Med, Dept Clin Neurosci, Providence, RI 02912 USA. Mem Hosp Rhode Isl, Div Neurol, Pawtucket, RI 02860 USA. VA Hudson Valley Healthcare Syst, Dept Psychol, Castle Point, NY 12511 USA. NINDS, Neurogenet Lab, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), Mayo Clin Jacksonville, Labs Neurogenet, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. RI Gwinn, Katrina/C-2508-2009; Hardy, John/C-2451-2009 NR 20 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD DEC PY 2002 VL 9 IS 2 BP 121 EP 123 AR PII S1353-8020(02)00003-2 DI 10.1016/S1353-8020(02)00003-2 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 619LM UT WOS:000179477500010 PM 12473404 ER PT J AU Autret, F Dauger, S Renolleau, S Eng, GV Kosofsky, BE Gressens, P Gaultier, C Gallego, J AF Autret, F Dauger, S Renolleau, S Eng, GV Kosofsky, BE Gressens, P Gaultier, C Gallego, J TI Ventilatory control in newborn mice prenatally exposed to cocaine SO PEDIATRIC PULMONOLOGY LA English DT Article DE cocaine; control of breathing; development; newborn; animal models ID CAROTID-BODY; NEONATAL RATS; RESPIRATORY CONTROL; BRAIN-DEVELOPMENT; CORTICAL-NEURONS; DEVELOPING SWINE; EARLY GESTATION; CEREBRAL WALL; IN-VITRO; HYPOXIA AB Infants born to mothers who used cocaine during pregnancy are at increased risk for neonatal death and respiratory impairments. Confounding factors such as multiple substance abuse make it difficult to isolate the effects of cocaine. We used a murine model to test the hypothesis that prenatal cocaine exposure may impair ventilatory responses to chemical stimuli in newborns. Seventy-two pregnant mice were randomly assigned to three groups: cocaine (COC), saline (SAL), and untreated (UNT). COC and SAL mice received subcutaneous injections of either 20 mg/kg of cocaine or a saline solution twice a day from gestational days 8-17. Ventilation (V'(E)) and tidal volume (V-T), both divided by body weight, and breath duration (T-TOT) were measured using whole-body plethysmography in freely moving COC (n = 47), SAL (n = 123), and UNT (n = 93) pups on postnatal day 2. The comparison between SAL and UNT pups showed significant differences in baseline breathing and in V'(E) responses to hypoxia, suggesting that maternal stress caused by injections affected the development of ventilatory control in pups. Baseline T-TOT was significantly longer in COC than in SAL pups. V'(E) responses to hypoxia were significantly smaller in COC than in SAL pups (+27 +/- 35% vs. +38 +/- 25%), but V'(E) responses to hypercapnia were similar (29 +/- 15% vs. 25 +/- 23%). Thus, breathing control was impaired by prenatal cocaine exposure, possibly because of abnormal development of neurotransmitter systems, such as the dopamine and serotonin systems. (C) 2002 Wiley-Liss, Inc. C1 Hop Robert Debre, INSERM, Lab Neurol & Physiol Dev, F-75019 Paris, France. Fac Med, Unite Rech Adaptat Physiol & Ccomportementales, Amiens, France. Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Hop Robert Debre, Serv Physiol, F-75019 Paris, France. RP Gallego, J (reprint author), Hop Robert Debre, INSERM, Lab Neurol & Physiol Dev, E9935,48 Blvd Serurier, F-75019 Paris, France. RI Gallego, Jorge/A-2239-2013; OI Gressens, Pierre/0000-0002-0909-4221 NR 53 TC 4 Z9 4 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 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD DEC PY 2002 VL 34 IS 6 BP 434 EP 441 DI 10.1002/ppul.10202 PG 8 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 619NA UT WOS:000179481100003 PM 12422341 ER PT J AU Biederman, J Heiligenstein, JH Faries, DE Galil, N Dittmann, R Emslie, GJ Kratochvil, CJ Laws, HF Schuh, KJ AF Biederman, J Heiligenstein, JH Faries, DE Galil, N Dittmann, R Emslie, GJ Kratochvil, CJ Laws, HF Schuh, KJ CA Atomoxetine ADHD Study Grp TI Efficacy of atomoxetine versus placebo in school-age girls with attention-deficit/hyperactivity disorder SO PEDIATRICS LA English DT Article DE atomoxetine; ADHD; school-age; girls; nonstimulant ID DEFICIT HYPERACTIVITY DISORDER; GENDER DIFFERENCES; ADHD; ADULTS; CHILDREN; BOYS AB Objective. The efficacy of atomoxetine was assessed in school-age girls with attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a potent inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors. Methods. A total of 291 children who were 7 to 13 years of age and met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for ADHD participated in I of 2 combined, double-blind, placebo-controlled, multisite, identical clinical trials. This intent-to-treat subset analysis examined the effects of atomoxetine versus placebo in 51 girls who were randomized to atomoxetine (n = 30) or placebo (n = 21) for 9 weeks. ADHD symptoms were assessed using parent- and investigator-rated scales. Results. Atomoxetine was superior to placebo on the following measures: the Attention-Deficit Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored Total Score; the Inattentive and Hyperactive/Impulsive subscales of the Attention-Deficit Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored Total Score; the ADHD Index subscale of the Conners' Parent Rating Scale-Revised: Short Form; and the Clinical Global Impressions of Severity of ADHD. Statistically significant efficacy was seen 1 week after randomization and remained so for the duration of the study. One patient from each of the atomoxetine and placebo groups discontinued the study as a result of an adverse event. Conclusion. Atomoxetine was found to be effective and well tolerated for the treatment of ADHD in school-age girls. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. Neurosci Inc, Bethesda, MD USA. Lilly Deutschland GmbH, Bad Homburg, Germany. Univ Hamburg, Psychosomat Dept, Childrens Hosp, Hamburg, Germany. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Nebraska, Med Ctr, Omaha, NE USA. RP Heiligenstein, JH (reprint author), Eli Lilly & Co, Lilly Corp Ctr, DC 2022, Indianapolis, IN 46285 USA. NR 25 TC 42 Z9 42 U1 0 U2 1 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 DEC PY 2002 VL 110 IS 6 AR e75 DI 10.1542/peds.110.6.e75 PG 7 WC Pediatrics SC Pediatrics GA 620TU UT WOS:000179549200010 PM 12456942 ER PT J AU Celedon, JC Litonjua, AA Ryan, L Weiss, ST Gold, DR AF Celedon, JC Litonjua, AA Ryan, L Weiss, ST Gold, DR TI Bottle feeding in the bed or crib before sleep time and wheezing in early childhood SO PEDIATRICS LA English DT Article DE bottle feeding; sleep time; wheezing ID GASTROESOPHAGEAL REFLUX; CHILDREN; ASTHMATICS; PERSISTENT; HISTORY; INFANTS; THERAPY; LIFE; RISK AB Objective. Bottle feeding in the bed or crib before sleep time has been associated with an increased risk of wheezing in the first year of life. We examined whether bottle feeding in the bed or crib before sleep time in the first year of life is associated with wheezing in the first 5 years of life. Methods. In a prospective cohort study of 448 children with parental history of atopy followed from birth, we examined the relation between the number of bimonthly parental reports of bottle feeding in the bed or crib before sleep time in the first year of life (range: 0-6 reports) and parental report of wheezing in the first 5 years of life. Additional outcome measures included recurrent wheezing (greater than or equal to2 episodes of wheezing in the previous year) and asthma (physician-diagnosed asthma and greater than or equal to1 episode of wheezing in the previous year) at the age of 5 years. Results. The risk of recurrent wheezing and asthma at 5 years of age increased significantly with each additional report of bottle feeding in the bed or crib before sleep time in the first year of life. The risk of wheezing between the ages of I and 5 years increased with each additional report of bottle feeding in the bed or crib before sleep time in the first year of life. As an example, a child whose parents reported bottle feeding in the bed or crib before sleep time on 3 occasions in the first year of life had 1.5 times higher risk of wheezing between the ages of 1 and 5 years than a child whose parents did not report bottle feeding in the bed or crib before sleep time in the first year of life (95% confidence interval for relative risk: 1.12-2.12). Conclusions. Among children with parental history of atopy, bottle feeding in the bed or crib before sleep time in the first year of life is a risk factor for recurrent wheezing and asthma at 5 years of age and a risk factor for wheezing between the ages of 1 and 5 years. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Celedon, JC (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NHLBI NIH HHS [KO1 HL04370-01A1]; NIAID NIH HHS [AIEHS35786] NR 16 TC 10 Z9 10 U1 0 U2 0 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 DEC PY 2002 VL 110 IS 6 AR e77 DI 10.1542/peds.110.6.e77 PG 5 WC Pediatrics SC Pediatrics GA 620TU UT WOS:000179549200012 PM 12456944 ER PT J AU Sipols, AJ Bayer, J Bennett, R Figlewicz, DP AF Sipols, AJ Bayer, J Bennett, R Figlewicz, DP TI Intraventricular insulin decreases kappa opioid-mediated sucrose intake in rats SO PEPTIDES LA English DT Article DE insulin; kappa opioid; palatability; food intake ID FOOD-INTAKE; SELF-STIMULATION; MESSENGER-RNA; PALATABILITY; BRAIN; DYNORPHIN-(1-13); SENSITIZATION; HYPERPHAGIA; SELECTION; AGONISTS AB The hormone insulin acts in the central nervous system (CNS) as a regulator of body adiposity and food intake. Recent work from our laboratory has provided evidence that one way by which insulin may decrease food intake is by decreasing the rewarding properties of food. Evidence from others suggests that endogenous opioids may mediate the palatable properties of foods, and insulin may decrease nonfood-related reward via interaction with some CNS kappa opioid systems. In the present study we examined the ability of insulin to interact with exogenous or endogenous kappa opioids to modulate feeding of palatable sucrose pellets by nondeprived rats. Insulin (5 mU intracerebroventricular (i.c.v.), t = -3 h) completely reversed the ability of the exogenous kappa agonist U50,488 (26 mug, i.c.v., t = -15 min) to stimulate 90-min sucrose feeding (211 +/- 32% reduced to 125 +/- 23% of 90-min baseline intake). Further, i.c.v. insulin (5 mU, t = -3 h) interacted with a subthreshold dose of the kappa receptor antagonist norbinaltorphimine (5 mug, i.c.v., t = -15 min) to decrease the 90-min sucrose intake baseline (77 +/- 11% versus 109 +/- 10% of 90 min baseline intake, insulin/norbinaltorphimine versus norbinaltorphimine). Together these studies provide new evidence that insulin in the CNS may decrease the action of CNS kappa opioid system(s) that mediate palatable feeding. (C) 2002 Elsevier Science Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Seattle, WA 98108 USA. Univ Latvia, Inst Clin & Expt Med, Riga, Latvia. Univ Latvia, Fac Med, Riga, Latvia. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, 1660 So Columbian Way,Seattle Div, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01 DK40963] NR 34 TC 26 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2002 VL 23 IS 12 BP 2181 EP 2187 AR PII S0196-9781(02)00246-2 DI 10.1016/S0196-9781(02)00246-2 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 641WJ UT WOS:000180769800013 PM 12535697 ER PT J AU Monks, NR Bordignon, SAL Ferraz, A Machado, KR Faria, DH Lopes, RM Mondin, CA de Souza, ICC Lima, MFS da Rocha, AB Schwartsmann, G AF Monks, NR Bordignon, SAL Ferraz, A Machado, KR Faria, DH Lopes, RM Mondin, CA de Souza, ICC Lima, MFS da Rocha, AB Schwartsmann, G TI Anti-tumour screening of Brazilian plants SO PHARMACEUTICAL BIOLOGY LA English DT Article DE cytotoxic activity; human tumour cell lines; organic and aqueous extracts; Brazil ID DRUG DISCOVERY; NATURAL-PRODUCTS AB Organic and aqueous extracts of 145 Brazilian plants (538 extracts) from 34 families were evaluated for anti-tumour activity against the human tumour cell lines HT29 and NCI-H460. Of the extracts tested, 117 (22%) demonstrated cytotoxicity against one or both of the cell lines at a concentration of 100 mug/ml.. Of special interest are the families Anacardiaceae, Annonaceae, Asteraceae, Celestraceae, Leguminosae (Fabaceae), Meliaceae and Myrtaceae, which contain a high proportion of active species. On the basis of these results we are further examining the cytotoxic species, with the objective of isolating and identifying the active phytochemicals. These results also confirm the continuing importance of natural product screening models, alongside targeted drug development, in the discovery of new anti-neoplastic pharmacophores. C1 Univ Luterana Brazil, Ctr Integrtado Canc, Canoas, Brazil. Hosp Clin Porto Alegre, S Amer Off Anticanc Drug Dev, Porto Alegre, RS, Brazil. RP Monks, NR (reprint author), Dana Farber Canc Inst, Smith Bldg,Rm 936A,44 Binney St, Boston, MA 02115 USA. RI Monks, Noel/B-5886-2013; Schwartsmann, Gilberto/G-4256-2016 OI Monks, Noel/0000-0001-6587-9827; Schwartsmann, Gilberto/0000-0002-7850-1644 NR 17 TC 11 Z9 12 U1 0 U2 5 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PD DEC PY 2002 VL 40 IS 8 BP 603 EP 616 PG 14 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 651TY UT WOS:000181339200010 ER PT J AU Mata, M Glorioso, JC Fink, DJ AF Mata, M Glorioso, JC Fink, DJ TI Targeted gene delivery to the nervous system using herpes simplex virus vectors SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE gene therapy; herpes simplex virus; neurotrophic factor; neuropathy; pain; enkephalin ID MEDIATED EXPRESSION; DELETION MUTANTS; MOTOR-NEURONS; TYPE-1 ICP27; DEGENERATION; BCL-2; PROTEINS AB Neurotrophic factors are highly potent macromolecules with protean effects. Although they are highly effective in vitro and in animal models in vivo, they have not been successfully applied to the treatment of human disease. Our laboratories have developed recombinant herpes simplex virus (HSV)-based vectors, that we have demonstrated may be used to deliver and express neurotrophic factor genes in dorsal root ganglion neurons to protect against the development of neuropathy in animal models, without causing systemic side effects. In a similar fashion, we have demonstrated that a vector expressing proenkephalin to mediate the release of opioid peptides from afferent nerve terminals in the spinal cord can be used to produce a localized antinociceptive effect in animal models of pain. Targeted gene delivery using HSV-based vectors offers a means to utilize short-lived peptides to produce specific effects in the nervous system. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, GREC, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Biochem & Mol Genet, Pittsburgh, PA 15261 USA. RP Fink, DJ (reprint author), S-520 BST,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 21 TC 11 Z9 12 U1 1 U2 1 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 DEC PY 2002 VL 77 IS 4-5 BP 483 EP 488 AR PII S0031-9384(02)00908-3 DI 10.1016/S0031-9384(02)00908-3 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 638TZ UT WOS:000180588400006 PM 12526987 ER PT J AU Pereira, P Reddy, VB Kounga, K Bello, Y Lerner, E AF Pereira, P Reddy, VB Kounga, K Bello, Y Lerner, E TI Maxadilan activates PAC1 receptors expressed in Xenopus laevis melanophores SO PIGMENT CELL RESEARCH LA English DT Article DE maxadilan; pituitary adenylate cyclase activating peptide; melanophores; Xenopus laevis; PACI receptor ID ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; VASODILATOR PEPTIDE; POLYPEPTIDE; LIGANDS AB Functional interactions between ligands and their cognate receptors can be investigated using the ability of melanophores from Xenopus laevis to disperse or aggregate their pigment granules in response to alterations in the intracellular levels of second messengers. We have examined the response of long-term lines of cultured melanophores from X. laevis to pituitary adenylate cyclase activating peptide ( PACAP), a neuropeptide with vasodilatory activity, and maxadilan, a vasodilatory peptide present in the salivary gland extracts of the blood feeding sand fly. Pituitary adenylate cyclase activating peptide increased the intracellular levels of cyclic adenosine monophosphate ( cAMP) and induced pigment dispersion in the pigment cells, confirming that melanophores express an endogenous PACAP receptor. Maxadilan did not induce a response in non-transfected melanophores. When the melanophores were transfected with complementary DNA (cDNA) from the three different members of the PACAP receptor family, maxadilan induced pigment dispersion specifically and cAMP accumulation in melanophores transfected with the cDNA for PAC1 receptors but not VPAC1 or VPAC2 receptors. melanophore line was generated that stably expresses the PAC1 receptor. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Lerner, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Cutaneous Biol Res Ctr, MGH E,13th St,Bldg 149, Charlestown, MA 02129 USA. FU NIAMS NIH HHS [R01 AR42005] NR 13 TC 11 Z9 13 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD DEC PY 2002 VL 15 IS 6 BP 461 EP 466 DI 10.1034/j.1600-0749.2002.02077.x PG 6 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 618HE UT WOS:000179412000010 PM 12453189 ER PT J AU Hsieh, MH Goodman, HM AF Hsieh, MH Goodman, HM TI Molecular characterization of a novel gene family encoding ACT domain repeat proteins in Arabidopsis SO PLANT PHYSIOLOGY LA English DT Article ID HOMOSERINE DEHYDROGENASE-I; SITE-DIRECTED MUTAGENESIS; ESCHERICHIA-COLI; THREONINE DEAMINASE; EFFECTOR-BINDING; D-3-PHOSPHOGLYCERATE DEHYDROGENASE; ACETOHYDROXYACID SYNTHASE; RESPONSE-REGULATOR; ASPARTOKINASE-I; NITROGEN AB In bacteria, the regulatory ACT domains serve as amino acid-binding sites in some feedback-regulated amino acid metabolic enzymes. We have identified a novel type of ACT domain-containing protein family in Arabidopsis whose members contain ACT domain repeats (the "ACR" protein family). There are at least eight ACR genes located on each of the five chromosomes in the Arabidopsis genome. Gene structure comparisons indicate that the ACR gene family may have arisen by gene duplications. Northern-blot analysis indicates that each member of the ACR gene family has a distinct expression pattern in various organs from 6-week-old Arabidopsis. Moreover, analyses of an ACR3 promoter-beta-glucuronidase (GUS) fusion in transgenic Arabidopsis revealed that the GUS activity formed a gradient in the developing leaves and sepals, whereas low or no GUS activity was detected in the basal regions. In 2-week-old Arabidopsis seedlings grown in tissue culture, the expression of the ACR gene family is differentially regulated by plant hormones, salt stress, cold stress, and light/dark treatment. The steady-state levels of ACR8 mRNA are dramatically increased by treatment with abscisic acid or salt. Levels of ACR3 and ACR4 mRNA are increased by treatment with benzyladenine. The amino acid sequences of Arabidopsis ACR proteins are most similar in the ACT domains to the bacterial sensor protein GlnD. The ACR proteins may function as novel regulatory or sensor proteins in plants. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Goodman, HM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NR 37 TC 21 Z9 35 U1 0 U2 3 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD DEC PY 2002 VL 130 IS 4 BP 1797 EP 1806 DI 10.1104/pp.007484 PG 10 WC Plant Sciences SC Plant Sciences GA 628JL UT WOS:000179990100025 PM 12481063 ER PT J AU Murphy, JC Neale, D Bromley, B Benacerraf, BR Copel, JA AF Murphy, JC Neale, D Bromley, B Benacerraf, BR Copel, JA TI Hypoechogenicity of fetal long bones: a new ultrasound marker for arthrogryposis SO PRENATAL DIAGNOSIS LA English DT Article DE osteoporosis; arthrogryposis; bone disease; fetal; ultrasound ID MULTIPLEX CONGENITA; DIAGNOSIS AB Objective To demonstrate osteopenia associated with arthrogryposis. Methods & Results We describe 3 cases of fetal arthrogryposis seen prenatally with the sonographic feature of severe hypoechogenicity of the long bones. This manifestation of presumed osteopenia is thought to represent osteoporosis secondary with absent fetal movement. Conclusion We describe hypoechogenicity of the fetal bones as a new sonographic feature of arthrogryposis, Copyright (C) 2002 John Wiley Sons. Ltd. C1 Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD DEC PY 2002 VL 22 IS 13 BP 1219 EP 1222 DI 10.1002/pd.492 PG 4 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 630KV UT WOS:000180106800011 PM 12478637 ER PT J AU Koepsell, T Reiber, G Simmons, KW AF Koepsell, T Reiber, G Simmons, KW TI Behavioral risk factors and use of preventive services among veterans in Washington State SO PREVENTIVE MEDICINE LA English DT Article DE medicine; preventive; veterans; health behavior ID SMOKING AB Background. Little is known about the special preventive health needs of U.S. veterans and the 3.6 million users of VA health care. Methods. The Washington State version of the 1999 Behavioral Risk Factor Survey included three new questions about veteran status and use of VA health care. Data on this population-based sample of 3,608 adults were used to compare sociodemographic, health, and behavioral characteristics between veterans and non-veterans and between VA users and nonusers. Results. Veterans were nearly 13 years older than nonveterans. VA users were socioeconomically worse off and had poorer health status than nonusers. Current smoking among males was more common among veterans than among nonveterans (24% vs 18%). This difference persisted after controlling for age, race, education, and income and held across all age groups. Use of several screening tests varied little in relation to veteran or VA user status. Conclusions. The BRFSS has become a rich source of data on veteran health. Veterans and VA users have distinct sociodemographic profiles that must be considered when comparing health-related characteristics. Cigarette smoking is especially prevalent among veterans-an excess unexplained by sociodemographic differences. (C) 2002 American Health Foundation and Elsevier Science (USA). C1 US Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Washington State Dept Hlth, Ctr Hlth Stat, Olympia, WA 98504 USA. RP Koepsell, T (reprint author), VAPSHCS, Seattle Epidemiol Res & Informat Ctr, Box 152E,1660 S Columbia Way, Seattle, WA 98108 USA. NR 8 TC 24 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2002 VL 35 IS 6 BP 557 EP 562 DI 10.1006/pmed.2002.1121 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 621ZJ UT WOS:000179621100004 PM 12460523 ER PT J AU Sonawalla, SB Farabaugh, AH Leslie, VM Pava, JA Matthews, JD Fava, M AF Sonawalla, SB Farabaugh, AH Leslie, VM Pava, JA Matthews, JD Fava, M TI Early drop-outs, late drop-outs and completers: differences in the continuation phase of a clinical trial (vol 26, pg 415, 2002) SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Correction DE age; clinical trial; completers; early drop-outs; late drop-outs; major depression ID DEPRESSION; TERMINATION; FLUOXETINE; COST AB Objective: The purpose of this study was to assess the differences between early (EDs), late drop-outs (LDs) and completers in the continuation phase of a clinical trial. Methods: The authors studied 119 outpatients who were treatment responders in an 8-week open trial with fluoxetine 20 mg/day, and who were then enrolled in a 26-week clinical trial comparing the efficacy of fluoxetine versus fluoxetine and cognitive behavior therapy (CBT). Patients were assessed using the Structured Clinical Interview for DSM-III-R-Axis I (SCID-Patient Edition), Hamilton Depression Rating Scale (HAMD-17) and the following self-rated scales: Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Anxiety Sensitivity Index (ASI) and the Symptom Questionnaire (SQ) prior to starting the 26-week continuation phase. We defined 'EDs' as patients who dropped out either at or prior to Visit 2 (which was at 2 months into the 6-month continuation phase); those dropping out at Visit 3 or later were defined as 'LDs' (ED< 2 months and LD > 2 months). The Kruskal-Wallis and the Mann-Whitney U tests were used for data analysis. Results: Of the 119 outpatients, 83 were completers (mean age: 42.1 +/- 9.0 years, 46 [55%] women, age of onset of major depressive disorder [MDD] = 24.3 +/- 12.5 years), 11 were EDs (mean age: 38.1 +/- 13.0 years, 4 [36%] women, age of onset of MDD = 22.0 +/- 11.1 years) and 25 were LDs (mean age: 35.2 +/- 10.4 years, 12 [48%] women, age of onset of MDD = 24.6 +/- 11.6 years). LDs were significantly younger than completers (P <.01). There was no significant difference in age between EDs and LDs, nor between EDs and completers. EDs and completers were depressed for a longer period of time compared to LDs (P<.05). EDs also had significantly greater overall impairment in social adjustment compared to completers (P<.05). Conclusions: Our data suggest that LDs are significantly younger than completers, although age is not a predictor between EDs and LDs. Further, EDs and completers are depressed for a longer duration than LDs, and EDs have significantly greater social impairment compared to completers. Our study identified some patient characteristics significantly associated with dropping out of a long-term clinical trial. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02114 USA. RP Sonawalla, SB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 23 TC 0 Z9 0 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD DEC PY 2002 VL 26 IS 7-8 BP 1413 EP + AR PII S0278-5846(02)00269-5 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 619HH UT WOS:000179470200025 ER PT J AU Petty, MA Lo, EH AF Petty, MA Lo, EH TI Junctional complexes of the blood-brain barrier: permeability changes in neuroinflammation SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; PROTEIN-KINASE-C; NEUTROPHIL TRANSENDOTHELIAL MIGRATION; CELL ADHERENS JUNCTIONS; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; TIGHT JUNCTION; MULTIPLE-SCLEROSIS AB A wide range of central nervous system (CNS) disorders include neuroinflammatory events that perturb blood-brain barrier (BBB) integrity. Mechanisms by which the BBB responds to physiological and pathological stimuli involve signaling systems in the tight and adherens junctions of the cerebral endothelium. In this review, we examine the molecular composition and regulatory mediators that control BBB permeability and assess how these mediators may be dysregulated in stroke, multiple sclerosis, brain tumors, and meningioencephalitis. An understanding of these molecular substrates in BBB regulation may lead to new approaches for enhancing CNS drug delivery and ameliorating brain edema after injury and inflammation. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Aventis Pharmaceut Inc, CNS Pharmacol, Bridgewater, NJ 08807 USA. Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Harvard, MA USA. RP Petty, MA (reprint author), Aventis Pharmaceut Inc, CNS Pharmacol, Route 202-206,POB 6800, Bridgewater, NJ 08807 USA. FU NINDS NIH HHS [R01-NS40529, R01-NS37074, P50-NS10828, R01-NS38731] NR 142 TC 197 Z9 200 U1 3 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD DEC PY 2002 VL 68 IS 5 BP 311 EP 323 AR PII S0301-0082(02)00128-4 DI 10.1016/S0301-0082(02)00128-4 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 648HL UT WOS:000181145000001 PM 12531232 ER PT J AU Krykbaev, RA Tsantili, P Jeffrey, PD Margolies, MN AF Krykbaev, RA Tsantili, P Jeffrey, PD Margolies, MN TI Modifying specificity of antidigoxin antibodies using insertional mutagenesis SO PROTEIN SCIENCE LA English DT Article DE antibody specificity; bacteriophage display; digoxin; insertional mutagenesis ID AFFINITY; PROTEIN; DIGOXIN; COMPLEMENTARITY; REPERTOIRE; ANALOGS; REGION; SITE AB Certain antibodies (Abs) elicited using. the cardiac glycoside digoxin (digoxigenin tridigitoxoside) bind preferentially to analogs that differ from digoxin by substitutions on the cardenolide rings, the lactone, or by the presence or absence of attached sugars. Antibody 26-10 binds equally well to digoxin and digitoxin, which differ only by the presence in the former and the absence in the latter of an hydroxyl group at C12. Other antidigoxin Abs, however, can distinguish between these ligands by three orders of magnitude in binding. Inspection of the structure of Fab 26-10 complexed. with digoxin shows a gap in complementarity in the region between the digoxin O12 and LCDR3. We proposed that insertions in LCDR3 might result in Abs that bind digitoxin preferentially. We produced libraries of mutants displayed on bacteriophage which were randomized at LCDR3 and contained LCDR3 insertions. Mutants were selected by panning against digoxin and analogs. The mutants bound digitoxin preferentially up to 47-fold greater than digoxin. The mutants that bound well to digitoxin demonstrated a consensus sequence including the substitution of Trp at position L:94. Using site-directed mutagenesis, the binding to digitoxin was shown to be maximized by the combination of an insertion and L:Trp94 mutation, moving the L 94 side chain closer to digoxin. We also selected mutants that bound preferentially to gitoxin, which, like digitoxin, lacks the 12-hydroxyl, increasing relative binding to gitoxin up to 600-fold compared to the unmutated Ab 26-10. C1 Massachusetts Gen Hosp, Dept Surg, Antibody Engn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Cellular Biochem & Biophys, New York, NY 10021 USA. RP Margolies, MN (reprint author), Massachusetts Gen Hosp, Dept Surg, Antibody Engn Lab, 15 Parkman St,WACC 465, Boston, MA 02114 USA. FU NCI NIH HHS [CA24432]; NHLBI NIH HHS [HL47415] NR 27 TC 2 Z9 2 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 2002 VL 11 IS 12 BP 2899 EP 2908 DI 10.1110/ps.0223402 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 617FV UT WOS:000179352000014 PM 12441388 ER PT J AU Thompson, R Kane, VR Sayers, SL Brown, GK Coyne, JC Katz, IR AF Thompson, R Kane, VR Sayers, SL Brown, GK Coyne, JC Katz, IR TI An assessment of suicide in an urban VA Medical Center SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID OF-VETERANS-AFFAIRS; COMPLETED SUICIDE; PSYCHIATRIC-PATIENTS; AFFECTIVE-DISORDERS; PREVENTION CENTERS; YOUNG MEN; AGE; DEPRESSION; POPULATION; PREDICTION AB This study characterizes those patients of an urban VA Medical Center (VAMC) who had committed suicide. A cause-of-death search of the 1,075 veterans from the VAMCs case rolls who died during 1998 was conducted. For confirmed and suspected suicides, a chart review was conducted, noting psychiatric history and recent contact with the VAMC. Nineteen patients were either confirmed or suspected suicides. Few of these patients had made recent contact with the VAMC, although the majority of them had received psychiatric services from the VA at some time. The proportion of deaths due to suicide was similar in African American and White patients. Rates of suicide were elevated, primarily because of the high proportion of patients receiving psychiatric treatment. Elderly suicides were less likely to have had psychiatric services or previous psychiatric diagnoses than were younger suicides. Patients with past contact with psychiatric services may be especially at risk of suicide, particularly as contact with these services diminishes. Elderly patients in medical settings with undiagnosed or undertreated psychiatric disorders are also likely to have elevated risk for suicide. These findings demonstrate the importance of acknowledging that risk factors for suicide are specific to sites or populations; this information can be used in allocating resources for developing site-specific strategies for prevention. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illnes Res Educ & Clin Ctr, Philadelphia, PA USA. RP Thompson, R (reprint author), Univ Penn, Dept Psychiat, 11 Gates HUP,3400 Spruce St, Philadelphia, PA 19104 USA. RI Thompson, Richard/G-5408-2011 OI Thompson, Richard/0000-0003-0127-513X NR 36 TC 5 Z9 5 U1 1 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 2002 VL 65 IS 4 BP 326 EP 337 DI 10.1521/psyc.65.4.326.20234 PG 12 WC Psychiatry SC Psychiatry GA 631AU UT WOS:000180145100008 ER PT J AU Mueller, NJ Walter, RB Linscheid, P Schaffner, A Schoedon, G AF Mueller, NJ Walter, RB Linscheid, P Schaffner, A Schoedon, G TI Differential inhibition of constitutive and inducible nitric oxide synthase in vascular endothelial cells by analogues of tetrahydrobiopterin SO PTERIDINES LA English DT Article DE inflammation; vascular endothelial cell, nitric oxide synthase; pteridine; tetrahydrobiopterin; 4-amino-tetrahydrobiopterin, 5-methyl-tetrahydrobiopterin ID SMOOTH-MUSCLE CELLS; MESSENGER-RNA; PROINFLAMMATORY CYTOKINES; DEPENDENT VASODILATION; INDUCTION; CLONING; 4-AMINO-TETRAHYDROBIOPTERIN; MODULATION; EXPRESSION; ENDOTOXIN AB In the vasculature, a physiologic production of nitric oxide (NO) is maintained by endothelial nitric oxide synthase (eNOS). Induction of inducible nitric oxide synthase (iNOS) under inflammatory conditions (e.g. septic shock) resulting in high levels of nitric oxide (NO) is believed to be partly responsible for the pathophysiologic changes in the vascular system that occur under inflammatory conditions (e.g. septic shock). Both NOS isoforms are dependent on the obligatory cofactor tetrahydrobiopterin (BH4). We investigated the selectivity and potency of the BH4 analogues 4-amino-BH4 and 5-methyl-BH4 in inhibiting eNOS and iNOS in a murine vascular endothelial cell (MVEC) model expressing either eNOS or iNOS under physiologic and inflammatory conditions, respectively. Exogenous BH4 and its precursor sepiapterin both enhanced physiologic eNOS activity in resting MVEC, while 4-amino-BH4 slightly inhibited eNOS. 5-methyl-BH4 did not have any effect on eNOS. BH4, sepiapterin, and 5-methyl-BH4 had no effect on iNOS in inflammatory activated MVEC. In contrast, 4-amino-BH4 selectively inhibited iNOS with a potency comparable to the unselective NOS inhibitor Nomega-monomethyl-L-arginine (L-NMMA). The present study demonstrates that 4-amino-BH4 selectively and potently inhibits iNOS in vascular endothelial cells, while its effect on eNOS is minimal. The selective inhibition of iNOS is a promising strategy for the treatment of inflammatory conditions with high output of NO. Further in vivo studies are required to determine whether inhibition of NO production by analogues of BH4 offers any advantage compared to inhibition by L-arginine analogues. C1 Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Univ Hosp, Dept Med, Res Unit, Med Clin B, Zurich, Switzerland. RI Walter, Roland/C-1064-2008; Mueller, Nicolas/B-6864-2013 OI Walter, Roland/0000-0002-9268-3341; Mueller, Nicolas/0000-0002-1059-3191 NR 33 TC 0 Z9 0 U1 1 U2 1 PU INT SOC PTERIDINOLOGY PI INNSBRUCK PA C/O DR. ERIKA ARTNER-DWORZAK, UNIV INNSBRUCK, FRITZ PREGL STRASSE 3, A-6020 INNSBRUCK, AUSTRIA SN 0933-4807 J9 PTERIDINES JI Pteridines PD DEC PY 2002 VL 13 IS 4 BP 126 EP 132 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 667TN UT WOS:000182249100005 ER PT J AU Zarifi, MK Astrakas, LG Poussaint, TY du Plessis, A Zurakowski, D Tzika, AA AF Zarifi, MK Astrakas, LG Poussaint, TY du Plessis, A Zurakowski, D Tzika, AA TI Prediction of adverse outcome with cerebral lactate level and apparent diffusion coefficient in infants with perinatal asphyxia SO RADIOLOGY LA English DT Article DE asphyxia; brain, diffusion; brain, MR; cerebral palsy; infants, central nervous system; infants, newborn; magnetic resonance (MR), spectroscopy ID MAGNETIC-RESONANCE SPECTROSCOPY; ISCHEMIC BRAIN INJURY; PROTON MR SPECTROSCOPY; ACUTE HYPOXIA-ISCHEMIA; BIRTH ASPHYXIA; BLOOD-FLOW; NEUROLOGICAL OUTCOMES; ENERGY METABOLITES; HYDROGEN CLEARANCE; CONCURRENT CHANGES AB PURPOSE: To compare the predictive value for adverse outcome of quantitative cerebral lactate level and of apparent diffusion coefficient (ADC) in infants with perinatal asphyxia in the early postnatal period. MATERIALS AND METHODS: Lactate-choline ratios determined with proton magnetic resonance (MR) spectroscopy and ADC determined with diffusion MR imaging in basal ganglia and thalami in 26 full-term neonates (age range, 1-10 days) were compared with severity of acute hypoxic-ischemic encephalopathy and long-term clinical outcome. Differences in metabolites between outcome groups were evaluated with the nonparametric Kruskal-Wallis test and the Dunn test. Logistic regression was performed to examine the predictive value of each metabolite for differentiating normal from abnormal or fatal clinical outcome. The likelihood ratio test was used to assess the statistical significance of each metabolite. RESULTS: Logistic regression confirmed that lactate-choline ratio could be used to differentiate normal (n = 5) from abnormal (n = 14) or fatal (n = 6) outcome (P < .001) The probability of an adverse outcome exceeded 95% for a lactate-choline ratio of 1.0. Even when analyses were restricted to the early postnatal period, lactate-choline ratio was still a significant predictor of adverse outcome (P = .001). Although ADC images were useful in clinical examination of these infants, quantitative ADC were not predictive of outcome (P = .82). CONCLUSION: Higher lactate-choline ratios in basal ganglia and thalami of infants with perinatal asphyxia were predictive of worse clinical outcomes. Absolute ADC in the same brain regions did not indicate a statistically significant relationship with clinical outcome. Cerebral lactate level is useful in identifying infants who would benefit from early therapeutic intervention. (C) RSNA, 2002. C1 Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat, Childrens Hosp, Boston, MA 02115 USA. RP Tzika, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 51 Blossom St,Rm 261, Boston, MA 02114 USA. RI Astrakas, Loukas/F-5918-2011 NR 74 TC 63 Z9 69 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2002 VL 225 IS 3 BP 859 EP 870 DI 10.1148/radiol.2253011797 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 618MA UT WOS:000179420800034 PM 12461272 ER PT J AU Rabinov, JD Lee, PL Barker, FG Louis, DN Harsh, GR Cosgrove, GR Chiocca, EA Thornton, AF Loeffler, JS Henson, JW Gonzalez, RG AF Rabinov, JD Lee, PL Barker, FG Louis, DN Harsh, GR Cosgrove, GR Chiocca, EA Thornton, AF Loeffler, JS Henson, JW Gonzalez, RG TI In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: Initial experience SO RADIOLOGY LA English DT Article DE brain, biopsy; brain, effects of irradiation on; brain neoplasms, diagnosis; brain neoplasms, MR; brain neoplasms, MR spectroscopy; radiations, injurious effects ID MAGNETIC-RESONANCE SPECTROSCOPY; HUMAN BRAIN-TUMORS; IN-VIVO; PROTON SPECTROSCOPY; THERAPY; METABOLITES; QUANTITATION; MULTICENTER; RESOLUTION; NECROSIS AB PURPOSE: To determine if 3-T magnetic resonance (MR) spectroscopy allows accurate distinction of recurrent tumor from radiation effects in patients with gliomas of grade II or higher. MATERIALS AND METHODS: This blinded prospective study included 14 patients who underwent in vivo 3-T MR spectroscopy prior to stereotactic biopsy. All patients received a previous diagnosis of glioma (grade II or higher) and high-dose radiation therapy (>54 Gy). Prior to MR spectroscopy, conventional MR imaging was performed at 1.5 T to identify a gadolinium-enhanced region within the irradiated volume. Diagnosis was assigned by means of histopathologic analysis of the biopsy samples. RESULTS: Sixteen of 17 biopsy locations could be classified as predominantly tumor or predominantly radiation effect on the basis of the ratio of choline at the biopsy site to normal creatine level by using a value greater than 1.3 as the criterion for tumor. The remaining case, classified as recurrent tumor on the basis of MR spectroscopy results, was diagnosed as predominantly radiation effect on the basis of histopathologic findings. Disease in this patient progressed to biopsy-proven recurrence within 3 months. Overall, the ratio of choline at the biopsy site to normal creatine level was significantly elevated (unpaired two-tailed Student t test, P < .002) in those biopsy samples composed predominantly of tumor (n = 9) compared with those containing predominantly radiation effects (n = 8). The ratio was not significantly different between the two histopathologic groups. CONCLUSION: In vivo 3-T MR spectroscopy has sufficient spatial resolution and chemical specificity to allow distinction of recurrent tumor from radiation effects in patients with treated gliomas. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Therapy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA. RP Rabinov, JD (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Gray 2, Boston, MA 02114 USA. FU NCI NIH HHS [1R01CA83159, 1R21CA80113] NR 40 TC 87 Z9 99 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2002 VL 225 IS 3 BP 871 EP 879 DI 10.1148/radiol.2253010997 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 618MA UT WOS:000179420800035 PM 12461273 ER PT J AU Lee, MS Gunton, KB Fischer, DH Brucker, AJ AF Lee, MS Gunton, KB Fischer, DH Brucker, AJ TI Ocular manifestations of remote lighning strike SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID ELECTRICAL INJURIES C1 Univ Penn, Sch Med, Scheie Eye Inst, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Hosp, Philadelphia, PA 19107 USA. RP Brucker, AJ (reprint author), Univ Penn, Sch Med, Scheie Eye Inst, Philadelphia, PA 19104 USA. NR 7 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD DEC PY 2002 VL 22 IS 6 BP 808 EP 810 DI 10.1097/00006982-200212000-00023 PG 3 WC Ophthalmology SC Ophthalmology GA 627UQ UT WOS:000179954900023 PM 12476114 ER PT J AU Montezuma, SR Rizzo, JF Ziv, OR AF Montezuma, SR Rizzo, JF Ziv, OR TI Combined vitrectomy lens and contact electrode for ERG recording during surgery SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID LIGHT-EMITTING DIODE; ELECTRORETINOGRAM C1 Vet Adm Med Ctr Jamaica Plain, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. RP Rizzo, JF (reprint author), Vet Adm Med Ctr Jamaica Plain, Ctr Innovat Visual Rehabil, Mail Stop 151E,150 S Huntington Ave, Boston, MA 02130 USA. NR 16 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD DEC PY 2002 VL 22 IS 6 BP 828 EP 829 DI 10.1097/00006982-200212000-00034 PG 2 WC Ophthalmology SC Ophthalmology GA 627UQ UT WOS:000179954900034 PM 12476122 ER PT J AU Jain, RK AF Jain, RK TI Seminars in Oncology - Introduction SO SEMINARS IN ONCOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Steele Lab Tumor Biol, 100 Blossom St,Box 7, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2002 VL 29 IS 6 SU 16 BP 1 EP 2 DI 10.1053/sonc.2002.37762 PG 2 WC Oncology SC Oncology GA 648TK UT WOS:000181166500001 ER PT J AU Jain, RK AF Jain, RK TI Tumor angiogenesis and accessibility: Role of vascular endothelial growth factor SO SEMINARS IN ONCOLOGY LA English DT Review ID SOLID TUMORS; RADIATION; ANTIBODY; MACROMOLECULES; HIF-1-ALPHA; XENOGRAFTS; INCREASES; BLOCKADE; DELIVERY; VESSELS C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Steele Lab Tumor Biol, 100 Blossom St,Box 7, Boston, MA 02114 USA. NR 30 TC 214 Z9 221 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2002 VL 29 IS 6 SU 16 BP 3 EP 9 DI 10.1053/sonc.2002.37265 PG 7 WC Oncology SC Oncology GA 648TK UT WOS:000181166500002 PM 12516032 ER PT J AU Anderson, KC AF Anderson, KC TI Moving disease biology from the laboratory to the clinic SO SEMINARS IN ONCOLOGY LA English DT Review ID MULTIPLE-MYELOMA CELLS; MARROW STROMAL CELLS; THERAPEUTIC APPLICATIONS; DRUG-RESISTANCE; GROWTH; TUMOR; THALIDOMIDE; EXPRESSION; ADHESION C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Biney St, Boston, MA 02115 USA. NR 14 TC 18 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2002 VL 29 IS 6 SU 17 BP 17 EP 20 DI 10.1053/sonc.2002.34072 PG 4 WC Oncology SC Oncology GA 648TM UT WOS:000181166700005 PM 12520480 ER PT J AU Oh, WK Small, EJ AF Oh, WK Small, EJ TI Complementary and alternative therapies in prostate cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID CHINESE HERBAL PREPARATION; PC-SPES; ETHANOLIC EXTRACTS; CLINICAL-TRIAL; IN-VITRO; CELLS; SUPPLEMENTATION; APOPTOSIS; CARCINOMA; RISK C1 Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 34 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2002 VL 29 IS 6 BP 575 EP 584 DI 10.1053/sonc.2002.50007 PG 10 WC Oncology SC Oncology GA 627UD UT WOS:000179953800006 PM 12516040 ER PT J AU Monga, TN AF Monga, TN TI Special issue: Sexuality and cancer - Introduction SO SEXUALITY AND DISABILITY LA English DT Editorial Material C1 Houston VA Med Ctr, Rehabil Care Line Execut RCL117, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Monga, TN (reprint author), Houston VA Med Ctr, Rehabil Care Line Execut RCL117, 2002 Holcomb Blvd, Houston, TX 77030 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD WIN PY 2002 VL 20 IS 4 BP 235 EP 237 DI 10.1023/A:1021653312501 PG 3 WC Rehabilitation SC Rehabilitation GA 639EA UT WOS:000180613600002 ER PT J AU Henson, HK AF Henson, HK TI Breast cancer and sexuality SO SEXUALITY AND DISABILITY LA English DT Article DE breast cancer; sexuality; quality of life; female self-concept ID QUALITY-OF-LIFE; BODY-IMAGE; PSYCHOSOCIAL-ASPECTS; OVARIAN FAILURE; FOLLOW-UP; MASTECTOMY; THERAPY; SURGERY; IMPACT; RECONSTRUCTION AB Breast cancer is the most common form of cancer among women today. With early detection and advanced treatment options, survival rates are continuing to improve, but not without some long-term physical and emotional side effects. This article reviews the eftects. of breast cancer in general and breast cancer treatment specifically on sexuality in cancer survivors. How the cancer and its treatment may affect women at different ages is discussed. The psychological impact of cancer therapy on both the patient and her spouse are noted; and options for treatment interventions are reviewed. C1 Houston VA Med Ctr, Rehabil Care Line RCL117, Houston, TX 77030 USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. RP Henson, HK (reprint author), Houston VA Med Ctr, Rehabil Care Line RCL117, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 90 TC 47 Z9 48 U1 5 U2 10 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD WIN PY 2002 VL 20 IS 4 BP 261 EP 275 DI 10.1023/A:1021657413409 PG 15 WC Rehabilitation SC Rehabilitation GA 639EA UT WOS:000180613600004 ER PT J AU Monga, U AF Monga, U TI Sexual functioning in cancer patients SO SEXUALITY AND DISABILITY LA English DT Review DE cancer; sexual functioning; infertility; pregnancy ID SILDENAFIL CITRATE VIAGRA; INDUCED OVARIAN FAILURE; TESTICULAR CANCER; HODGKINS-DISEASE; SEMEN CRYOPRESERVATION; ERECTILE DYSFUNCTION; RADIATION-THERAPY; PROSTATE-CANCER; RETROPERITONEAL LYMPHADENECTOMY; CYCLOPHOSPHAMIDE THERAPY AB Controversy exists regarding the extent and nature of sexual problems in cancer patients. The incidence of sexual problems varies in published studies irrespective of the cancer site. Most of the studies are retrospective and descriptive in design and many do not take into account the preexisting physical, psychosocial, sexual, and marital problems. However, it is clear that sexual problems are common in cancer patients and may be caused by all the available treatment options. Management of sexual problems in this patient population has not been systematically studied. This article reviews prevalence of sexual problems that result from various treatment modalities (such as surgery, radiotherapy, and chemotherapy) and describes guidelines for management of sexuality related issues in cancer survivors. C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. RP Monga, U (reprint author), Radiotherapy Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 126 TC 10 Z9 11 U1 5 U2 7 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD WIN PY 2002 VL 20 IS 4 BP 277 EP 295 DI 10.1023/A:1021609530248 PG 19 WC Rehabilitation SC Rehabilitation GA 639EA UT WOS:000180613600005 ER PT J AU Tan, G Waldman, K Bostick, R AF Tan, G Waldman, K Bostick, R TI Psychosocial issues, sexuality, and cancer SO SEXUALITY AND DISABILITY LA English DT Article DE psychological; sexuality; cancer ID LONG-TERM SURVIVORS; QUALITY-OF-LIFE; BREAST-CANCER; PROSTATE-CANCER; GYNECOLOGIC CANCER; SELF-SCHEMA; DEPRESSION; WOMEN; MEN; DYSFUNCTION AB It is well-documented in the literature that psychosocial factors play a significant role in the development and progress of, adaptation to, and survival from cancer Cancer and its treatment often lead to psychiatric co-morbidity, precipitate spiritual crisis, compel lifestyle changes, and disrupt family and social relationships. One area most affected by cancer is quality of life, including sexual functioning. Cancer treatment may increase risk of infertility, difficulty with intimacy and sexuality, employment discrimination, increased general distress, and fear of recurrence. In addition to describing the psychosocial impact of cancer and its treatment, and discussing how psychosocial factors affect sexuality and sexual functioning, this paper concludes with options available to manage the sexual problems and related psychosocial issues in order to restore optimal sexual functioning. C1 Houston VA Med Ctr, Mental Hlth Care Line, Houston, TX 77030 USA. Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA. RP Tan, G (reprint author), Houston VA Med Ctr, Mental Hlth Care Line, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 96 TC 21 Z9 22 U1 3 U2 6 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD WIN PY 2002 VL 20 IS 4 BP 297 EP 318 DI 10.1023/A:1021661614318 PG 22 WC Rehabilitation SC Rehabilitation GA 639EA UT WOS:000180613600006 ER PT J AU Shah, MK Hugghins, SY AF Shah, MK Hugghins, SY TI Characteristics and outcomes of patients with Goodpasture's syndrome SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID ANTIGLOMERULAR BASEMENT-MEMBRANE; ANTIBODY-MEDIATED DISEASE; NORMAL RENAL-FUNCTION; PULMONARY HEMORRHAGE; INDUCED GLOMERULONEPHRITIS; WEGENERS-GRANULOMATOSIS; DIABETES-MELLITUS; LUNG HEMORRHAGE; GBM NEPHRITIS; VASCULITIS AB Background. Goodpasture's syndrome is a rare disorder characterized by pulmonary hemorrhage, glomerulonephritis, and antiglomerular basement membrane antibodies. Methods. Case reports of Goodpasture's syndrome between 1993 and 2000 were identified using MEDLINE. Each case was reviewed for clinical manifestations, laboratory features, pathophysiology, treatment options, and outcomes. Results. Eighty-five cases of Goodpasture's syndrome were reported in the English language literature. The mean age of patients in this review was 44 years. Most patients had multiple risk factors. Smoking was strongly associated with pulmonary hemorrhage. Most patients presented with hemoptysis and crackles. More than 90% had antiglomerular basement membrane antibodies, and 80% had crescenteric glomerulonephritis on renal biopsy. Conclusion. Most patients were treated with immunosuppression and plasma exchange and were alive at follow-up. Patients-with either pulmonary or renal signs and symptoms should be evaluated for Goodpasture's syndrome, since early diagnosis-allows prompt treatment and improved outcome. C1 Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Shah, MK (reprint author), 10 Summer St,Suite 303S, Malden, MA 02148 USA. NR 81 TC 22 Z9 26 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD DEC PY 2002 VL 95 IS 12 BP 1411 EP 1418 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 645JJ UT WOS:000180972200012 PM 12597309 ER PT J AU Samsa, G Oddone, EZ Horner, R Daley, J Henderson, W Matchar, DB AF Samsa, G Oddone, EZ Horner, R Daley, J Henderson, W Matchar, DB TI To what extent should quality of care decisions be based on health outcomes data? Application to carotid endarterectomy SO STROKE LA English DT Article DE carotid endarterectomy; complications; quality improvement ID AFFAIRS SURGICAL RISK; VOLUME; ADJUSTMENT; MORTALITY; OPERATIONS; HOSPITALS; PROGRAM AB Background and Purpose-Most quality improvement methods implicitly assume that facilities with high complication rates are likely to have substandard processes of care, a stable characteristic that, in the absence of intervention, will persist over time. We assessed the extent to which this holds true for carotid endarterectomy. Methods-Using data from the Department of Veterans Affairs National Surgical Quality Improvement Project, we classified facilities on the basis of 30-day complications of carotid endarterectomy (stroke, myocardial infarction, death) during 1994 to 1995 (period 1, n=3389) and then compared these groups of facilities for complication rates during 1996 to 1997 (period 2, n=4453). Results-Despite wide variation in facility-specific complication rates, the correlation between rates in periods 1 and 2 was low (Spearman correlation coefficient, 0.04; P=0.01) Facility-specific rates did not show greater correlation when we examined only facilities with higher volumes patients in different clinical categories (asymptomatic, transient ischemic attack, stroke). Comorbid illness profiles were similar between the 2 time periods. Conclusions-Most of the facility-specific differences in complication rates in period 1 were not maintained into period 2. Many apparent quality improvement problems may not be as large as they first appear, especially when based on few complications per facility. The inability, in practice, to estimate complication rates at a high degree of precision is a fundamental difficulty for clinical policy making regarding procedures with complication rates such as carotid endarterectomy. C1 Duke Univ, Med Ctr, Ctr Clin Hlth Policy Res, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. Vet Adm Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Partners Healthcare Syst, Boston, MA USA. Boston VA Med Ctr, Boston, MA USA. Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Outcomes Program, Denver, CO 80202 USA. RP Samsa, G (reprint author), Duke Univ, Med Ctr, Ctr Clin Hlth Policy Res, Suite 220,1st Union Bldg,2200 W Main St, Durham, NC 27705 USA. OI Matchar, David/0000-0003-3020-2108 NR 14 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2002 VL 33 IS 12 BP 2944 EP 2949 DI 10.1161/01.STR.0000038095.20079.F6 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 625QL UT WOS:000179827100043 PM 12468795 ER PT J AU Franklin, ME Gonzalez, JJ AF Franklin, ME Gonzalez, JJ TI Laparoscopic placement of hepatic artery catheter for regional chemotherapy infusion - Technique, benefits, and complications SO SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES LA English DT Article ID PROSPECTIVE RANDOMIZED TRIAL; COLORECTAL LIVER METASTASES; INTRAARTERIAL FLOXURIDINE; PUMP PLACEMENT; CANCER; CARCINOMA; FLUOROURACIL; SURVIVAL AB Approximately 15% to 18% of patients diagnosed with colorectal cancers present with metastases confined to the liver. Although many may undergo a liver resection procedure, some will not be candidates for surgery or will have recurrence of liver disease within the first 2 years after liver metastasis resection. For this subset of patients, regional hepatic chemotherapy, including intra-arterial chemotherapy, has been shown to improve control of the disease and, in some cases, proton,, survival. With the advent of laparoscopic surgery and its application to more and more advanced procedures, the possibility of laparoscopic placement of a chemotherapy infusion catheter in the hepatic artery with all the advantages of a minimally invasive approach appears to be a viable alternative in our hands. From November 1993 through February 2002, 20 patients (12 male, 8 female) successfully underwent laparoscopic placement of a hepatic artery infusion catheter at the Texas Endosurgery Institute. Correct placement of the catheter was confirmed by methylene blue injections via the hepatic artery catheter at the time of surgery. Chemotherapy was generally initiated in the immediate postoperative period. Mean age was 68.3 years (range, 46-82). Twelve of the patients (60%) had previously undergone abdominal surgery. There were 27 major laparoscopic procedures performed at the time of hepatic artery catheter placement. There were no conversions to an open procedure. Mean operative time was 186 minutes (range, 125-280). and mean blood loss was 132 mL (range, 20-300). These values include the 27 major concurrent laparoscopic procedures performed at the time of catheter placement, including 18 cholecystectomies, 7 colectomies, and 2 liver resections. Median hospital stay was 3 days (range, 3-25). with a median return to regular diet of 3 days. There were no intraoperative complications and no deaths secondary to catheter placement. There were 2 late complications, for an overall rate of 10%. For all 17 patients with residual hepatic disease whose chemotherapy was successfully instituted, regression of the metastases was evident by abdominal computed tomographic criteria and CEA levels. Laparoscopic hepatic artery catheterization is both feasible and safe. It incurs all the benefits of a minimally invasive procedure and can be performed at the time of laparoscopic colectomy to avoid the necessity of a second procedure. C1 Texas Endosurg Inst, San Antonio, TX 78222 USA. Univ Texas, Hlth Care Ctr, Dept Surg, San Antonio, TX 78285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Franklin, ME (reprint author), Texas Endosurg Inst, 4242 E Southcross,Suite 1, San Antonio, TX 78222 USA. NR 33 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1530-4515 J9 SURG LAPARO ENDO PER JI Surg. Laparosc. Endosc. Pct. Tech. PD DEC PY 2002 VL 12 IS 6 BP 398 EP 407 DI 10.1097/00129689-200212000-00003 PG 10 WC Surgery SC Surgery GA 629LD UT WOS:000180050400003 PM 12496545 ER PT J AU Aiello, LP AF Aiello, LP TI The potential role of PKC beta in diabetic retinopathy and macular edema SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE diabetes; diabetic retinopathy; macular edema; protein kinase C ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; RETINAL NEOVASCULARIZATION; VASCULAR COMPLICATIONS; CELL GROWTH; IN-VIVO; INHIBITION; ACTIVATION; ISOFORM; PHOTOCOAGULATION AB Diabetic retinopathy is one of the most debilitating complications of diabetes mellitus. Despite major advances in understanding the pathogenesis of this disease and the efficacy of current therapies, diabetic retinopathy remains the leading cause of new-onset blindness among working-age people. The mainstay of current therapy, laser photocoagulation, is useful in preventing blindness and severe vision loss but is not often effective in restoring lost visual acuity. In addition, troublesome side effects and potentially serious complications may occur. Diabetic retinopathy is characterized by a progression of abnormalities. Nonproliferative retinopathy results from a series of biochemical and cellular changes that ultimately cause progressive retinal ischemia. The subsequent elaboration of growth factors in response to ischemia leads to the development of proliferative retinopathy, which is characterized by aberrant neovacularization of the retina-potentially leading to severe, irreversible visual loss. Increased retinal vascular leakage may also occur at any stage in this process, resulting in macular edema and possible progressive visual impairment. Although numerous biochemical factors are thought to play a role in the development of retinopathy, activation of protein kinase C (PKC), specifically the beta isoform of PKC (PKC beta), is implicated for both the early and late-stage manifestations of retinopathy. Studies suggest that orally administered LY333531, a beta-isoform specific PKC inhibitor, may be effective in ameliorating retinopathy progression, proliferation, and retinal vascular leakage. The status of ongoing clinical trials aimed at addressing the efficacy of PKC beta with regard to diabetes-induced retinal complications and perspectives on the role of PKC beta are presented. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 48 TC 95 Z9 95 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD DEC PY 2002 VL 47 SU 2 BP S263 EP S269 AR PII S0039-6257(02)00391-0 DI 10.1016/S0039-6257(02)00391-0 PG 7 WC Ophthalmology SC Ophthalmology GA 627LT UT WOS:000179935200005 PM 12507628 ER PT J AU Mandelkern, M Raines, J AF Mandelkern, Mark Raines, Jonathan TI Positron Emission Tomography in Cancer Research and Treatment SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article AB Positron emission tomography (PET), the imaging of pharmaceuticals labeled with positron-emitting radionuclides, is a rapidly growing modality for the diagnosis and management of cancer. PET yields high-quality images characterizing substrate metabolism, cellular proliferation, receptor density, and other parameters that can be used to identify cancer and evaluate its response to therapies. The technique mainly utilized in cancer management is FOG-PET, which exploits the abnormal glucose metabolism of cancer cells first characterized by Warburg. We discuss the principles of PET, the currently available instrumentation and radiopharmaceuticals, the efficacy of FOG-PET in the management of cancer, and the prospects for near-term advances in cancer using PET. C1 [Mandelkern, Mark] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA. [Mandelkern, Mark; Raines, Jonathan] Greater Los Angeles VA Healthcare Syst, Dept Imaging, Los Angeles, CA USA. RP Mandelkern, M (reprint author), Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA. EM markm@uci.edu NR 97 TC 9 Z9 10 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2002 VL 1 IS 6 BP 423 EP 439 PG 17 WC Oncology SC Oncology GA V28FZ UT WOS:000208668000003 PM 12625770 ER PT J AU Kim, YR Savellano, MD Weissleder, R Bogdanov, A AF Kim, Young Ro Savellano, Mark D. Weissleder, Ralph Bogdanov, Alexei, Jr. TI Steady-state and Dynamic Contrast MR Imaging of Human Prostate Cancer Xenograft Tumors: A Comparative Study SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE angiogenesis; MRI; optical imaging; interstitial space; absolute blood volume; water exchange AB Understanding tumor vascular physiology is critically important for developing non-invasive, molecularly targeted diagnostic agents and therapies. In this study, using three different human prostate cancer xenografts (MDA PCa 2b, PC3, and LnCap), structural and physiological parameters of neoplastic vasculature and interstitum were explored with a widely available magnetic resonance imaging (MRI) pulse sequence (3D SPGR: spoiled gradient echo). Using dual injection technique employing two T1 contrast agents of different molecular masses (Weissleder, R., Cheng, H. C., Marecos, E., Kwong, K. K., Bogdanov, A., Jr. Eur. J. Cancer 34, 1448-1454 (1998)), steady state (SS) MRI measurements and dynamic contrast agent enhancement (DCE) MRI measurements were simultaneously acquired and analyzed using a two-compartment model for calculating parameters reflecting tumoral architecture and physiology. In particular, interstitial volume and vascular permeability were independently quantified using these two different MRI techniques. Relative vascular water exchange rate, calculated by the flip angle (FA) dependence of measured blood volume using SS technique, and vascular permeability of contrast agent, extrapolated from DCE MRI, were compared. It was found that the SS and DCE techniques were comparable and yielded similar qualitative results for extravascular compartment (interstitial volume). However, the permeability (water exchange rate and contrast agent vascular permeability) values were in disagreement. The results of MR studies are important for interpreting optical imaging results obtained using long-circulating of tumor-associated enzymatic activity. C1 [Kim, Young Ro; Savellano, Mark D.; Weissleder, Ralph; Bogdanov, Alexei, Jr.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5406, Charlestown, MA 02129 USA. EM abogdanov@helix.mgh.harvard.edu FU NIH [T32CA79443, RO1CA74424, P50CA86355, R21CA85657] FX Authors gratefully acknowledge the financial support from NIH grants T32CA79443, RO1CA74424, P50CA86355, R21CA85657. NR 23 TC 10 Z9 10 U1 3 U2 5 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2002 VL 1 IS 6 BP 489 EP 495 PG 7 WC Oncology SC Oncology GA V28FZ UT WOS:000208668000009 PM 12625776 ER PT J AU Lewandrowski, KU Bondre, S Hile, DD Thompson, BMJ Wise, DL Tomford, WW Trantolo, DJ AF Lewandrowski, KU Bondre, S Hile, DD Thompson, BMJ Wise, DL Tomford, WW Trantolo, DJ TI Porous poly(propylene fumarate) foam coating of orthotopic cortical bone grafts for improved osteoconduction SO TISSUE ENGINEERING LA English DT Article ID DEMINERALIZED BONE; ALLOGRAFTS; OSTEOINDUCTION; CEMENT AB A porous biodegradable scaffold coating for perforated and demineralized cortical bone allografts could maintain immediate structural recovery and subsequently allow normal healing and remodeling by promoting bony ingrowth and avoiding accelerated graft resorption. This new type of osteoconductive surface modification should improve allograft incorporation by promoting new bone growth throughout the biodegradable scaffold, hence encasing the graft with the recipient's own bone. We investigated the feasibility of augmenting orthotopically transplanted cortical bone grafts with osteoconductive biodegradable polymeric scaffold coatings. Five types of bone grafts were prepared: type 1, untreated fresh-frozen cortical bone grafts (negative control); type II, perforated and partially demineralized cortical bone grafts without additional coating (positive control); type III, perforated and partially demineralized cortical bone coated with a low-porosity poly(propylene fumarate) (PPF) foam; type IV, perforated and partially demineralized cortical bone coated with a medium-porosity PPF foam; and type V, perforated and partially demineralized cortical bone coated with a high-porosity PPF foam. Grafts were implanted into the rat tibial diaphysis. Fixation was achieved with an intramedullary threaded K-wire. Two sets of animals were operated on. Animals were killed in groups of eight with one set being killed 12 weeks, and the other 16 weeks, postoperatively. Radiographic, histologic, and histomorphometric analyses of grafts showed that the amount of new bone forming around the foam-coated grafts was significantly higher than that in the type I control group (uncoated) or that in type II group (perforated and partially demineralized cortical bone grafts). Although all foam formulations appeared initially equally osteoconductive, histologic evaluation of medium-porosity PPF foam-based coatings appeared to result in a sustained response 16 weeks postoperatively. Significant resorption was present in perforated and partially demineralized cortical bone graft allografts, with some accompanying new bone formation occurring primarily within the laser holes. Therefore, PPF foam-coated cortical bone grafts appeared to be better protected from excessive bone resorption, as frequently seen with invasion of fibrovascular tissue. Biomechanical analysis of the PPF foam-coated grafts corroborated findings of the morphometric analysis in that the failure strength at the allograft-host bone junction sites of all PPF-coated cortical bone grafts was higher than in the uncoated controls. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthoped Res Labs, Boston, MA 02114 USA. Albany Med Coll, Albany, NY 12208 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [AR 45062, R43 AR 46608] NR 28 TC 9 Z9 9 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 2002 VL 8 IS 6 BP 1017 EP 1027 DI 10.1089/107632702320934119 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 621EW UT WOS:000179576400012 PM 12542947 ER PT J AU Rong, Y Sugumaran, G Silbert, JE Spector, M AF Rong, Y Sugumaran, G Silbert, JE Spector, M TI Proteoglycans synthesized by canine intervertebral disc cells grown in a type I collagen-glycosaminoglycan matrix SO TISSUE ENGINEERING LA English DT Article ID AGGREGATING PROTEOGLYCANS; EXTRACELLULAR-MATRIX; NUCLEUS PULPOSUS; CHONDROCYTES; CULTURE; HETEROGENEITY; REGENERATION; METABOLISM; ALGINATE; ANNULUS AB The objective, of this study was to determine the characteristics of proteoglycans synthesized by canine annulus fibrosus cells expanded in number in monolayer culture through passage 4 and subsequently grown in a type I collagen-glycosaminoglycan matrix to be employed for tissue engineering. Newly synthesized [S-35]sulfate-labeled proteoglycans were analyzed by gel chromatography, including sequential digestion with enzymes and nitrous acid. After 1 week in culture, the percentage of cell-associated,, aggregated proteoglycans synthesized in type I collagen-glycosaminoglycan matrices was 52% compared with 38% by the cells in monolayer. The percentage of aggregated proteoglycan in each group increased only slightly with the addition of exogenous hyaluronic acid, but remained significantly different from each other. There were at least three different hydrodynamic sizes of proteoglycans both in the collagen-glycosaminoglycan matrix and in monolayer; the average size was larger in the collagen matrices and the glycosaminoglycan chains were longer. The proteoglycans contained chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate. The results provide a foundation for future investigations of collagen-glycosaminoglycan matrices for intervertebral disc tissue engineering. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Singapore Gen Hosp, Dept Expt Surg, Singapore 0316, Singapore. Edith Nourse Rogers Mem Vet Adm Med Ctr, Bedford, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol Allergy, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, MRB 106,75 Francis St, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR41649] NR 24 TC 42 Z9 42 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 2002 VL 8 IS 6 BP 1037 EP 1047 DI 10.1089/107632702320934137 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 621EW UT WOS:000179576400014 PM 12542949 ER PT J AU Thompson, CA Colon-Hernandez, P Pomerantseva, I MacNeil, BD Nasseri, B Vacanti, JP Oesterle, SN AF Thompson, CA Colon-Hernandez, P Pomerantseva, I MacNeil, BD Nasseri, B Vacanti, JP Oesterle, SN TI A novel pulsatile, laminar flow bioreactor for the development of tissue-engineered vascular structures SO TISSUE ENGINEERING LA English DT Article ID ARTERIES AB Exposure of vascular cell-seeded, tubular, biodegradable polymers to pulsatile flow conditions has been proposed as a method to develop tissue-engineered blood vessels by "maturing" structural integrity, and increasing collagen content, suture retention, burst pressure, and tissue formation. These in vitro tissue-engineered arteries demonstrate contractile responses to pharmacologic agents and express markers of vascular differentiation. Current methods to induce pulsatile flow in a bioreactor system are limited by the creation of nonphysiologic pressure waveforms and noncompliant reservoirs to house the tissue-engineered vascular constructs. We have developed a novel method for the in vitro development of tubular vascular structures by using a mechanical ventilator to induce pulsatile, laminar flow into a fluid column, resulting in pressurized waveforms similar to mammalian physiology. The vascular constructs are housed in semicompliant tubing to facilitate an additional variable of circumferential stretch as a potential signaling mechanism. This approach more closely approximates mammalian physiology and we hypothesize that it will facilitate mechanical signaling necessary for the development of tissue-engineered vessels for clinical applications. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Catheterizat Labs,Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tissue Engn Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Thompson, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Catheterizat Labs,Cardiac Unit, Blake 950,55 Fruit St, Boston, MA 02114 USA. NR 9 TC 26 Z9 28 U1 2 U2 7 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 2002 VL 8 IS 6 BP 1083 EP 1088 DI 10.1089/107632702320934173 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA 621EW UT WOS:000179576400018 PM 12542953 ER PT J AU Dzik, S AF Dzik, S TI Nitric oxide: Nature's third respiratory gas SO TRANSFUSION LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Blood Transfus Serv, Boston, MA 02114 USA. NR 1 TC 5 Z9 5 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2002 VL 42 IS 12 BP 1532 EP 1533 DI 10.1046/j.1537-2995.2002.00288.x PG 2 WC Hematology SC Hematology GA 626TF UT WOS:000179888700002 PM 12473129 ER PT J AU Lam, BCH Blumwald, E AF Lam, BCH Blumwald, E TI Domains as functional building blocks of plant proteins SO TRENDS IN PLANT SCIENCE LA English DT Editorial Material ID PLECKSTRIN HOMOLOGY DOMAIN; DYNAMIN-LIKE PROTEIN; TRANSCRIPTION FACTORS; ARABIDOPSIS-THALIANA; SIGNALING DOMAINS; DATABASE; FAMILIES; IDENTIFICATION; TRAFFICKING; RECOGNITION AB Emerging evidence in eukaryotic systems suggests that many proteins of diverse cellular processes are made up of protein domains that are well defined in both sequence and structure. This article updates the identification of many 'classic' eukaryotic protein domains in various plant cellular processes, with particular emphasis on the non-catalytic categories. We discuss the importance of domains to plant-protein functions and cellular networking, and the emergence of plant-specific, domains. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Calif Davis, Dept Pomol, Davis, CA 95616 USA. RP Lam, BCH (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM eblumwald@ucdavis.edu NR 30 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1360-1385 J9 TRENDS PLANT SCI JI Trends Plant Sci. PD DEC PY 2002 VL 7 IS 12 BP 544 EP 549 AR PII S1360-1385(02)02337-3 DI 10.1016/S1360-1385(02)02337-3 PG 6 WC Plant Sciences SC Plant Sciences GA 624XW UT WOS:000179788200012 PM 12475496 ER PT J AU Krieger, JN Ross, SO Penson, DF Riley, DE AF Krieger, JN Ross, SO Penson, DF Riley, DE TI Symptoms and inflammation in chronic prostatitis/chronic pelvic pain syndrome SO UROLOGY LA English DT Article ID NONBACTERIAL PROSTATITIS; PROSTATODYNIA; MEN; CLASSIFICATION; OBSTRUCTION; VALIDATION AB Objectives. To evaluate the possibility that patients with inflammatory and noninflammatory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) might present with different symptoms. Patients with CP/CPPS present with characteristic symptoms without bacteriuria. The new National Institutes of Health consensus suggests that CP/CPPS can be divided into inflammatory and noninflammatory categories. Methods. Standardized symptom surveys were completed by 130 subjects who met the criteria for CP/CPPS after clinical examination and urethral, urine, expressed prostatic secretion (EPS), and seminal fluid analysis evaluations. Results. When classified by either EPS or postprostatic massage urine (VB3) findings, subjects with and without inflammation had similar symptoms. However, when classified using the combination of EPS, VB3, and seminal fluid analysis, subjects with inflammatory CP/CPPS had more severe (P <0.02) and more frequent symptoms, in particular, difficulty reaching erection (P <0.01), weak urinary stream (P <0.01), urinary frequency (P = 0.03), and penile pain (P = 0.04). Conclusions. The increased severity and frequency of symptoms among patients with inflammatory CP/ CPPS provide empirical support for the new consensus classification on the basis of the combination of EPS, VB3, and seminal fluid analysis findings. (C) 2002, Elsevier Science Inc. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA 98108 USA. Univ Washington, Dept Urol, Sch Med, Seattle, WA 98108 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Pathobiol, Seattle, WA 98108 USA. RP Krieger, JN (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Urol Sect, 112 GU,1660 S Columbian Way,Campus Mail Box 35828, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01 DK38955] NR 25 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 2002 VL 60 IS 6 BP 959 EP + AR PII S0090-4295(02)01963-5 DI 10.1016/S0090-4295(02)01963-5 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 626TC UT WOS:000179888500004 PM 12475649 ER PT J AU Vaughan, D Imperato-Mcginley, J McConnell, J Matsumoto, AM Bracken, B Roy, J Sullivan, M Pappas, F Cook, T Daurio, C Meehan, A Stoner, E Waldstreicher, J AF Vaughan, D Imperato-Mcginley, J McConnell, J Matsumoto, AM Bracken, B Roy, J Sullivan, M Pappas, F Cook, T Daurio, C Meehan, A Stoner, E Waldstreicher, J TI Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia SO UROLOGY LA English DT Article ID ACUTE URINARY RETENTION; EFFICACY; SAFETY; NEED AB Objectives. To evaluate the effects of finasteride, a specific type II 5-alpha-reductase inhibitor, on symptoms of benign prostatic hyperplasia, prostate volume, and urinary flow during a 7 to 8-year period. Methods. A total of 190 men with symptomatic benign prostatic hyperplasia and enlarged prostates entered one of two Phase II double-blind 3 to 6-month studies. Of these, 156 patients continued taking open-label finasteride, and more than 70 patients completed 7 to 8 years of treatment. The symptoms were scored using a patient self-administered modified Boyarsky symptom questionnaire. Prostate volume was measured by magnetic resonance imaging or ultrasonography, and the maximal urinary flow rate was assessed noninvasively. Results. Treatment with finasteride for 7 to 8 years led to sustained improvement in symptoms, reduction in prostate volume (28% from baseline), and increased urinary flow (median 2.5 mL/s from baseline). Decreases in dihydrotestosterone (86%) and prostate-specific antigen (54%) levels were also maintained. Long-term finasteride treatment was safe and generally well tolerated. Conclusions. Long-term treatment with finasteride was well tolerated and resulted in durable symptom relief and improvement in prostate volume and urinary flow. (C) 2002, Elsevier Science Inc. C1 Merck Res Labs, Rahway, NJ 07065 USA. Cornell Univ, Ctr Med, New York, NY USA. Univ Texas, Dallas, TX 75230 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. Univ Cincinnati, Edmond, OK USA. Mercy Res Clin, San Diego, CA USA. RP Waldstreicher, J (reprint author), Merck Res Labs, RY34-A212,126 E Lincoln Ave, Rahway, NJ 07065 USA. NR 17 TC 43 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 2002 VL 60 IS 6 BP 1040 EP 1044 AR PII S0090-4295(02)01971-4 DI 10.1016/S0090-4295(02)01971-4 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 626TC UT WOS:000179888500021 PM 12475666 ER PT J AU Cario, E Gerken, G Podolsky, DK AF Cario, E Gerken, G Podolsky, DK TI "For whom the bell tolls!" - Innate defense mechanisms and survival strategies of the intestinal epithelium against lumenal pathogens SO ZEITSCHRIFT FUR GASTROENTEROLOGIE LA English DT Review DE innate immunity; intestinal epithelium; host defense; mucosa; toll-like receptors; nods; apoptosis ID INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; LIPOPOLYSACCHARIDE-BINDING PROTEIN; PROINFLAMMATORY GENE-EXPRESSION; PATTERN-RECOGNITION RECEPTOR; SIGNAL-TRANSDUCTION PATHWAY; DERMAL ENDOTHELIAL-CELLS; BACTERIAL LIPOPOLYSACCHARIDE; ESCHERICHIA-COLI; IMMUNE-RESPONSES AB The intestinal epithelium serves as an essential defensive barrier of the mucosal immune system that forms a bipolar interface between the diverse populations of microbes of the lumen and subjacent immune cells present in the lamina propria. Intestinal epithelial cells express various pattern recognition receptors poised to recognize microbial "pathogen-associated molecular patterns" as "non-self'' and to rapidly initiate innate immune responses of survival and active defense strategies against lumenal pathogens. Current understanding of the variety of innate immune features present in intestinal epithelium to maintain homeostasis is summarized and the mechanisms through which dysregulation may play a central role in initiation and perpetuation of inflammatory bowel disease are discussed. C1 Univ Essen Gesamthsch, Div Gastroenterol & Hepatol, Inst Grp 1CR9, D-45147 Essen, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. RP Cario, E (reprint author), Univ Essen Gesamthsch, Div Gastroenterol & Hepatol, Inst Grp 1CR9, Virchowstr 171, D-45147 Essen, Germany. FU NIDDK NIH HHS [DK41557, DK43351] NR 150 TC 31 Z9 31 U1 0 U2 0 PU DEMETER VERLAG GEORG THIEME VERLAG PI STUTTGART PA PETRA SCHLAGENHAUF, RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0044-2771 J9 Z GASTROENTEROL JI Z. Gastroent. PD DEC PY 2002 VL 40 IS 12 BP 983 EP 990 DI 10.1055/s-2002-36159 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 636EF UT WOS:000180441000006 PM 12518264 ER PT J AU Choe, EY Schoenberger, ES Groopman, JE Park, IW AF Choe, EY Schoenberger, ES Groopman, JE Park, IW TI HIV Nef inhibits T cell migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 NEF; SIGNALING PATHWAYS; TYROSINE KINASE; SH3 DOMAIN; PROTEIN; ACTIVATION; CHEMOTAXIS; RECEPTOR; EXPRESSION; COMPLEX AB Nef is a viral regulatory protein of the human immunodeficiency virus (HIV) that has been shown to contribute to disease progression. Among its putative effects on T cell functions are the down-regulation of CD4 and major histocompatibility class I surface molecules. These effects occur in part via Nef interactions with intracellular signaling molecules. We sought to better characterize the effects of HIV Nef on T cell function by examining chemotaxis in response to stromal cell-derived factor-1alpha (SDF-1alpha) as well as CXCR4 signaling molecules. Here, we report the novel observation that HIV Nef inhibited chemotaxis in response to SDF-1alpha in both Jurkat T cells and primary peripheral CD4+ T lymphocytes. Our data indicate that HIV Nef altered critical downstream molecules in the CXCR4 pathway, including focal adhesion kinases. These findings suggest that HIV Nef may blunt the T cell response to chemokines. Because T lymphocyte migration is an integral component of host defense, HIV Nef may thereby contribute to the pathogenesis of AIDS. C1 Harvard Univ, Sch Med, Inst Med,Div Expt Med, Beth Israel Deaconess Med Ctr,BIDMC, Boston, MA 02115 USA. RP Groopman, JE (reprint author), Harvard Univ, Sch Med, Inst Med,Div Expt Med, Beth Israel Deaconess Med Ctr,BIDMC, 4 Blackfan Circle,Rm 351, Boston, MA 02115 USA. EM jgroopma@caregroup.harvard.edu FU NHLBI NIH HHS [HL53745, HL61940]; NIDA NIH HHS [DA5008] NR 50 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 2002 VL 277 IS 48 BP 46079 EP 46084 DI 10.1074/jbc.M204698200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620JB UT WOS:000179529300050 PM 12354773 ER PT J AU Stanislaus, R Gilg, AG Singh, AK Singh, I AF Stanislaus, R Gilg, AG Singh, AK Singh, I TI Immunomodulation of experimental autoimmune encephalomyelitis in the Lewis rats by Lovastatin SO NEUROSCIENCE LETTERS LA English DT Article DE Lovastatin; statins; autoimmunity; Th1; Th2; experimental autoimmune encephalomyelitis; multiple sclerosis; splenocytes ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; MULTIPLE-SCLEROSIS; MICE; CELLS; CYTOKINES; IL-6 AB Previous studies; have demonstrated the immunomodulatory potential of Lovastatin, a hydroxy methyl glutaryl-CoA reductase inhibitor, in lessening the clinical and histological manifestations in the neuroinflammatory animal model experimental autoimmune encephalomyelitis (EAE) (Neurosci. Lett., 269 (1999) 71, and J. Neurosci. Res., 66 (2001) 155). To determine the mechanism behind the observed amelioration of EAE by Lovastatin, we examined the cytokine profile of stimulated splenocytes from control, EAE and Lovastatin treated EAE rats. Splenocytes from Lovastatin-treated EAE rats showed decreased levels of interferon-gamma, a Th1 type cytokine, while interleukin (IL)-10, a Th2 type cytokine, was markedly increased as compared to untreated EAE animals. In addition, we also observed reduced levels of IL-6 and nitric oxide production in lipopolysaccharide-stimulated splenocytes isolated from Lovastatin-treated animals. This study documents for the first time that Lovastatin induces a bias towards Th2 cytokines ex vivo, and as a result may be of therapeutic value for cell-mediated diseases such as multiple sclerosis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40810] NR 17 TC 52 Z9 60 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 29 PY 2002 VL 333 IS 3 BP 167 EP 170 AR PII S0304-3940(02)00943-6 DI 10.1016/S0304-3940(02)00943-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 619MR UT WOS:000179480200004 PM 12429374 ER PT J AU Altfeld, M Allen, TM Yu, XG Johnston, MN Agrawal, D Korber, BT Montefiori, DC O'Connor, DH Davis, BT Lee, PK Maier, EL Harlow, J Goulder, PJR Brander, C Rosenberg, ES Walker, BD AF Altfeld, M Allen, TM Yu, XG Johnston, MN Agrawal, D Korber, BT Montefiori, DC O'Connor, DH Davis, BT Lee, PK Maier, EL Harlow, J Goulder, PJR Brander, C Rosenberg, ES Walker, BD TI HIV-1 superinfection despite broad CD8(+) T-cell responses containing replication of the primary virus SO NATURE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; TYPE-1 INFECTION; IMMUNE-RESPONSES; VIREMIA; LYMPHOCYTES; DISCONTINUATION; VACCINATION; PREVENTION; MACAQUES; AIDS AB Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection(1-3). A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8(+) T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8(+) T-cell responses. The declining CD8(+) T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8(+) T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02129 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. Nuffield Dept Med, Dept Pediat, Oxford OX3 7LJ, England. RP Walker, BD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02129 USA. RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778; o'connor, david/0000-0003-2139-470X NR 27 TC 233 Z9 241 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 28 PY 2002 VL 420 IS 6914 BP 434 EP 439 DI 10.1038/nature01200 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 619TZ UT WOS:000179494700044 PM 12459786 ER PT J AU Rottbauer, W Saurin, AJ Lickert, H Shen, XT Burns, CG Wo, ZG Kemler, R Kingston, R Wu, C Fishman, M AF Rottbauer, W Saurin, AJ Lickert, H Shen, XT Burns, CG Wo, ZG Kemler, R Kingston, R Wu, C Fishman, M TI Reptin and pontin antagonistically regulate heart growth in zebrafish embryos SO CELL LA English DT Article ID CHROMATIN REMODELING COMPLEX; BETA-CATENIN; BRANCH MIGRATION; BINDING-PROTEIN; COLON-CARCINOMA; RUVB PROTEINS; DNA HELICASE; CYCLIN D1; C-MYC; EXPRESSION AB Organ size is precisely regulated during development, but the control mechanisms remain obscure. We have isolated a mutation in zebrafish, liebeskummer (lik), which causes development of hyperplastic embryonic hearts. lik encodes Reptin, a component of a DNA-stimulated ATPase complex. The mutation activates ATPase activity of Reptin complexes and causes a cell-autonomous proliferation of cardiomyocytes to begin well after progenitors have fashioned the primitive heart tube. With regard to heart growth, beta-catenin and Pontin, a DNA-stimulated ATPase that is often part of complexes with Reptin, are in the same genetic pathways. Pontin reduction phenocopies the cardiac hyperplasia of the lik mutation. Thus, the Reptin/Pontin ratio serves to regulate heart growth during development, at least in part via the beta-catenin pathway. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Max Planck Inst Immunbiol, Dept Mol Embryol, D-79108 Freiburg, Germany. NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Fishman, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. RI Lickert, Heiko/K-9045-2013 FU NHLBI NIH HHS [5R01HL49579, T32 HL007208, 1R01HL63206]; NIDDK NIH HHS [5R01DK55383] NR 40 TC 112 Z9 115 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 27 PY 2002 VL 111 IS 5 BP 661 EP 672 DI 10.1016/S0092-8674(02)01112-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 621MV UT WOS:000179594500008 PM 12464178 ER PT J AU Sheetz, MJ King, GL AF Sheetz, MJ King, GL TI Molecular understanding of hyperglycemia's adverse effects for diabetic complications SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; GLYCATION END-PRODUCTS; ALDOSE REDUCTASE INHIBITOR; NERVE-CONDUCTION-VELOCITY; PKC-BETA INHIBITOR; VITAMIN-E SUPPLEMENTATION; EPITHELIUM-DERIVED FACTOR; ELEVATED GLUCOSE-LEVELS; NITRIC-OXIDE SYNTHASE AB Diabetic complications are the major cause of morbidity and mortality in persons with diabetes. Chronic hyperglycemia is a major initiator of diabetic microvascular complications (eg, retinopathy, neuropathy, nephropathy). Glucose,processing uses a variety of diverse metabolic pathways; hence, chronic hyperglycemia can induce multiple cellular changes leading to complications. Several predominant well-researched theories have been proposed to explain how hyperglycemia can produce the neural and vascular derangements that a re hallmarks of diabetes. These theories can be separated into those that emphasize the toxic effects of hyperglycemia and its pathophysiological derivatives (such as oxidants,,hyperosmolarity, or glycation products) on tissues directly and those that ascribe pathophysiological importance to a sustained alteration in cell signaling pathways (such as changes in phospholipids or kinases) induced by the products of glucose metabolism. This article summarizes these theories and the potential therapeutic interventions that may prevent diabetic complications in the presence of hyperglycemia, control of which is often difficult with current therapeutic options. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Lilly Res Labs, Indianapolis, IN USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Room 4504, Boston, MA 02215 USA. FU NEI NIH HHS [R01 EY05110] NR 151 TC 494 Z9 513 U1 12 U2 126 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 27 PY 2002 VL 288 IS 20 BP 2579 EP 2588 DI 10.1001/jama.288.20.2579 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 618AL UT WOS:000179394500025 PM 12444865 ER PT J AU Wiest, FC Ferris, TG Gokhale, M Campbell, EG Weissman, JS Blumenthal, D AF Wiest, FC Ferris, TG Gokhale, M Campbell, EG Weissman, JS Blumenthal, D TI Preparedness of internal medicine and family practice residents for treating common conditions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PRACTITIONERS SELF-ASSESSMENT; PRIMARY-CARE; AUSCULTATORY SKILLS; KNOWLEDGE; OUTCOMES; VALIDITY; PREFERENCES; PHYSICIANS; TRAINEES; FEMALE AB Context Although both internal medicine (IM) and family practice (FP) physicians frequently provide care for the same common adult conditions, IM. and FP residency programs differ in their training emphases. Objective To assess differences in IM and FP residents' self-perceived preparedness to diagnose and treat common adult medical conditions. Design, Setting, and Participants Cross-sectional analysis of a national survey administered in the spring of 1998 to residents in their final year of residency at US academic health centers. A total of 279 IM residents in 25 programs and 326 FP residents in 75 programs responded to the survey. Main Outcome Measures Residents' self-rated preparedness to diagnose and treat 4 inpatient conditions (acute myocardial infarction, diabetic ketoacidosis, acute asthma, and acute renal failure) and 8 outpatient conditions (diabetes, hypertension, low back pain, vaginitis, headache, depression, upper respiratory tract infection, and hyperlipidemia), controlling for resident sex, race/ethnicity, US medical school graduate status, intent to subspecialize, and estimates of exposure to patients in inpatient and outpatient settings. Results Internal medicine residents were more likely to report being very prepared for all 4 inpatient conditions (Pless than or equal to.001), while FP residents were more likely to report being very prepared for 5 of 8 outpatient conditions (Pless than or equal to.05). Differences between IM and FP residents persisted in multivariate Analyses for all inpatient conditions and some outpatient conditions. Exposure to patients in inpatient and outpatient settings varied by specialty and was significantly associated with resident self-report of preparedness for a majority of conditions investigated. Conclusions Internal medicine and FP residents report differences in preparedness to manage common adult conditions. These differences were consistent with the emphasis on an inpatient setting for IM residents and on off ice-based care for FP residents. C1 Massachusetts Gen Hosp, Div Gen Med, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Washington, Dept Med, Seattle, WA USA. Dept Vet Affairs Puget Sound Healthcare Syst, Robert Wood Johnson Clin Scholars Program, Seattle, WA USA. RP Ferris, TG (reprint author), Massachusetts Gen Hosp, Div Gen Med, Inst Hlth Policy, 50 Staniford St, Boston, MA 02114 USA. FU PHS HHS [00850] NR 31 TC 47 Z9 48 U1 0 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 NOV 27 PY 2002 VL 288 IS 20 BP 2609 EP 2614 DI 10.1001/jama.288.20.2609 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 618AL UT WOS:000179394500031 PM 12444870 ER PT J AU Caldera, A Dec, GW AF Caldera, A Dec, GW TI Hyperhomocysteinemia and transplant coronary artery disease SO TRANSPLANTATION LA English DT Article ID ALLOGRAFT VASCULAR-DISEASE; ENDOTHELIAL-CELL INJURY; CHRONIC-RENAL-FAILURE; PROTEIN-C ACTIVATION; METHYLENETETRAHYDROFOLATE REDUCTASE; HEART-TRANSPLANTATION; TOTAL HOMOCYSTEINE; RISK FACTOR; RECIPIENTS; PLASMA AB Background. Transplant coronary artery disease (TCAD) is a major cause of morbidity and mortality among heart transplant recipients. A variety of immunologic and nonimmunologic mechanisms are involved in the pathogenesis of the disease. Hyperhomocysteinemia has been recognized as an important risk factor for atherosclerotic vascular disease. The purpose of this article is to evaluate the prevalence of hyperhomocysteinemia in heart transplant recipients but more specifically to assess the published literature regarding the association between hyperhomocysteinemia and TCAD. Methods. A MEDLINE search using the key words hyperhomocysteinemia, transplant coronary artery disease, and heart transplant was performed. Results. Hyperhomocysteinemia has been commonly found among heart transplant recipients (average prevalence 51% to 76%). Worsening renal function and impaired vitamin metabolism seem to be the major causes of hyperhomocysteinemia in this particular population. TCAD has been found to be more prevalent and severe among patients with higher serum homocysteine levels. Vitamin supplementation is safe and effective in reducing serum homocysteine among heart transplant recipients. Conclusion. A large, long-term, double-blind, placebo-controlled prospective trial aimed at assessing the clinical significance of homocysteine-lowering therapy on the natural history of TCAD seems warranted. C1 Harvard Univ, Massachusetts Gen Hosp, Heart Failure & Transplantat Unit, Boston, MA 02114 USA. Albert Einstein Med Ctr, Dept Med, Philadelphia, PA 19141 USA. RP Dec, GW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Heart Failure & Transplantat Unit, Bigelow 645,55 Fruit St, Boston, MA 02114 USA. NR 50 TC 7 Z9 8 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2002 VL 74 IS 10 BP 1359 EP 1364 DI 10.1097/01.TP.0000034032.95956.6F PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 618TG UT WOS:000179432900001 PM 12451231 ER PT J AU Buhler, LH Spitzer, TR Sykes, M Sachs, DH Delmonico, FL Tolkoff-Rubin, N Saidman, SL Sackstein, R McAfee, S Dey, B Colby, C Cosimi, AB AF Buhler, LH Spitzer, TR Sykes, M Sachs, DH Delmonico, FL Tolkoff-Rubin, N Saidman, SL Sackstein, R McAfee, S Dey, B Colby, C Cosimi, AB TI Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; DONOR LEUKOCYTE INFUSIONS; NONLETHAL PREPARATIVE REGIMEN; MIXED CHIMERISM; CONDITIONING REGIMEN; CYNOMOLGUS MONKEYS; LONG-TERM; RECIPIENTS; LEUKEMIA; TRANSFUSIONS AB Background. Two patients with end-stage renal disease secondary to multiple myelomas were treated with combined kidney and bone marrow transplantation in an effort to achieve donor-specific allotolerance through the induction of mixed lymphohematopoietic chimerism. Methods. Two female patients (55 and 50 years of age) with end-stage renal disease secondary to kappa light-chain multiple myelomas received a nonmyeloablative conditioning regimen that consisted of 61 mg/kg cyclophosphamide intravenously (IV) on days -5 and -4; 15 mg/kg equine anti-thymocyte globulin (ATGAM) IV on days -1, +1, and +3; and thymic irradiation (700 cGy) on day -1. On day 0, the recipients underwent kidney transplantation, followed by IV in fusion of donor bone marrow (2.7 x 10(8) and 3.8 x 10(8) /kg nucleated cells, respectively) obtained from a human leukocyte antigen (HILA)-matched sibling. Cyclosporine A was administered IV at a dose of 5 mg/kg on days - 1, then continued orally at 8 to 12 mg/kg per day until days +73 and +77, respectively, after which no further immunosuppression was given. Donor leukocyte infusions (1 x 10(7) /kg CD3 + T cells) were administered in an attempt to enhance the graft-versus-myeloma effect (days +66 and + 112 in the first patient and day + 78 in the second patient). Hematopoietic chimerism was monitored weekly by microsatellite assays. Results. Multilineage lymphohematopoietic chimer ism (50%-80% donor CD3+ or CD3- cells, or both) was first detected during the second posttransplant week and was maintained for approximately 12 weeks, after which there was a gradual decline to undetectable. levels (< 1% donor cells) after day 105 in the first patient and after day 123 in the second patient. In both recipients, the blood urea nitrogen and creatinine levels returned to normal within 3 days. No rejection episodes have occurred. Quantification of urinary kappa light chains revealed a decline from 28 mg/dL to undetectable levels (< 2.5 mg/dL) within 29 days in the first case and from 99.8 mg/dL to < 10 mg/dL within 50 days in the second case. Both patients continue with normal kidney function and sustained anti-tumor responses, while receiving no immunosuppression for nearly 4 years and 2 years, respectively. Conclusions. This nonmycloablative regimen followed by combined HLA-matched donor bone marrow and renal allotransplantation is the first example of an intentional and clinically applicable approach to inducing renal allograft tolerance and achieving potent and sustained antitumor effects in patients with multiple myeloma. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Bone Marrow Transplantat Unit, Boston, MA USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Histocompatibil Lab, Boston, MA USA. RP Cosimi, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [1R01 CA79988-01A1]; NHLBI NIH HHS [5R01 HL63430-02, P01 HL18646]; NIAID NIH HHS [R01 AI37692] NR 31 TC 192 Z9 203 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2002 VL 74 IS 10 BP 1405 EP 1409 DI 10.1097/01.TP.0000034627.37442.A4 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 618TG UT WOS:000179432900011 PM 12451240 ER PT J AU Tremblay, J Chen, HF Peng, JZ Kunes, J Vu, MD Sarkissian, SD deBlois, D Bolton, AE Gaboury, L Marshansky, V Gouadon, E Hamet, P AF Tremblay, J Chen, HF Peng, JZ Kunes, J Vu, MD Sarkissian, SD deBlois, D Bolton, AE Gaboury, L Marshansky, V Gouadon, E Hamet, P TI Renal ischemia-reperfusion injury in the rat is prevented by a novel immune modulation therapy SO TRANSPLANTATION LA English DT Article ID ACUTE TUBULAR-NECROSIS; ISCHEMIA/REPERFUSION INJURY; CELL-DEATH; BLOOD-PRESSURE; FAILURE; APOPTOSIS; HEAT; KIDNEY; EXPRESSION; PRETREATMENT AB Background. Vasogen Inc.'s (Mississauga, Ontario, Canada) immune modulation therapy (IMT) is a therapy in which cells from the patient's own blood are modified by ex vivo exposure to specific physicochemical stressors, including oxidation, ultraviolet (UV) light, and an elevated temperature. The therapy has been shown to have a beneficial effect in models of inflammation and vascular diseases. This study tested the hypothesis that IMT can prevent renal ischemia-reperfusion (I/R) injury in rats. Methods. Whole blood was collected from syngeneic age-matched donors by cardiac puncture. it was treated with a combination of controlled physiochemical stressors consisting of elevated temperature, a gas mixture of medical oxygen containing ozone, and UV light. The treated blood (150 muL) was injected in the gluteal muscle. Control animals received the same volume of untreated blood or physiological saline. Transient (45 or 60 minutes) left-renal ischemia was produced with simultaneous contralateral nephrectomy in treated and control spontaneously hypertensive rats (SHR). Young and old male and female rats were studied. Plasma creatinine, diuresis, and the survival rates of each group were compared. Renal apoptosis-necrosis was estimated by DNA laddering, histology, and in situ terminal deoxynucleotidyl transferase assay. mRNA levels of several regulators of apoptosis-regeneration were determined in control and post-ischemic kidneys by Northern blotting. Results. IMT pretreatment of SHR significantly reduced renal I/R injury compared with equivalent placebo treatments consisting of untreated blood- or saline-injected SHR, as evidenced by a significant increase of the survival rate curves in young and old male SHR, which correlated with 24-hour postischemic diuresis. The increases in plasma creatinine following renal 1111 were significantly lower in IMT-treated young male and old female SHR compared with saline or untreated blood-injected controls. Dilution analysis showed that the protective effect of treated blood was lost by dilution. Loss of epithelial cells was reduced in IMT-treated rats, with a significant decline in the peak of apoptosis 12 hours after acute ischemic renal injury. IMT did not modify the pattern of mRNA levels of several genes involved in the inflammation and regeneration processes.. Conclusion. Our data demonstrate that IMT prevents the destruction of kidney tissue and the resulting animal death caused by renal I/R injury. C1 CHUM, Hotel Dieu, Ctr Rech, Mol Med Lab, Montreal, PQ, Canada. Acad Sci Czech Republ, Prague, Czech Republic. Vasogen Inc, Mississauga, ON, Canada. Massachusetts Gen Hosp, Charlestown, MA USA. RP Hamet, P (reprint author), CHUM, Hotel Dieu, Ctr Rech, Mol Med Lab, 3850 St Urbain, Montreal, PQ, Canada. RI Kunes, Jaroslav/B-7079-2012; Tremblay, Johanne/E-2154-2013; Cossette, Suzanne/I-8008-2016 NR 71 TC 13 Z9 16 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2002 VL 74 IS 10 BP 1425 EP 1433 DI 10.1097/01.TP.0000034208.20704.E1 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 618TG UT WOS:000179432900015 PM 12451244 ER PT J AU Bagley, J Tian, C Sachs, DH Iacomini, J AF Bagley, J Tian, C Sachs, DH Iacomini, J TI T cells mediate resistance to genetically modified bone marrow in lethally irradiated recipients SO TRANSPLANTATION LA English DT Article ID IMMUNE-RESPONSE; MIXED CHIMERISM; TOLERANCE; CD40; LIGAND; LYMPHOCYTES; EXPRESSION; ALLOGRAFTS; INDUCTION; ANTIBODY AB Background. In order for gene therapy to attain clinical relevance, efficient engraftment and long-term survival of cells that express transduced genes of interest must be achieved. In this study, we examined the extent to which host T cells affect engraftment of syngeneic bone marrow cells engineered to express a retrovirally transduced allogeneic major histocompatibility complex class-I gene. Methods. B10.AKM mice were preconditioned with lethal irradiation or lethal irradiation plus transient CD4 and CD8 T-cell depletion in addition to CD40-CD154 costimulatory blockade and were then reconstituted with syngeneic bone marrow cells transduced with retroviruses that carried the gene that encoded H-2K(b) (K-b). Expression of K-b on bone marrow-derived cells was then analyzed, and induction of tolerance to K-b was evaluated. Results. Mice conditioned using CD4 and CD8 T-cell depletion in addition to CD40-CD154 costimulatory blockade and lethal irradiation showed a significant increase in the frequency of bone marrow-derived cells that expressed K-b when compared to animals that received lethal irradiation alone. Survival of allogeneic skin grafts that expressed K-b was significantly prolonged in animals conditioned with anti-CD4, anti-CD8, and co-stimulatory blockade in addition to lethal irradiation (median survival time, 81 days) when compared to mice that received irradiation alone (mean survival time, 31 days; P = 0.001). Conclusions. Radioresistant host T cells significantly affect the ability to induce tolerance by gene therapy by affecting engraftment of transduced cells that expressed allogeneic major histocompatibility complex class-I genes in the absence of host T-cell depletion and costimulatory blockade, even after lethal irradiation. Thus, radioresistant host T cells are a significant barrier to engraftment of transduced bone marrow progenitors and to the induction of tolerance by gene therapy. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149-5210,13th St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI43619, T32 AI07529, R01 AI44268] NR 25 TC 13 Z9 13 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 NOV 27 PY 2002 VL 74 IS 10 BP 1454 EP 1460 DI 10.1097/01.TP.0000034625.87602.3B PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 618TG UT WOS:000179432900019 PM 12451248 ER PT J AU Nieland, TJF Penman, M Dori, L Krieger, M Kirchhausen, T AF Nieland, TJF Penman, M Dori, L Krieger, M Kirchhausen, T TI Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; CHOLESTERYL ESTER UPTAKE; APOPROTEIN-A-I; SCAVENGER RECEPTOR; CELLULAR UPTAKE; DEFICIENT MICE; EXPRESSION; METABOLISM; SURFACE; BINDING AB The high-density lipoprotein (HDL) receptor, scavenger receptor, class B, type I (SR-BI), mediates both the selective uptake of lipids, mainly cholesterol esters, from HDL to cells and the efflux of cholesterol from cells to lipoproteins. The mechanism underlying these lipid transfers is distinct from classic receptor-mediated endocytosis, but it remains poorly understood. To investigate SR-BI's mechanism of action and in vivo function, we developed a high-throughput screen to identify small molecule inhibitors of SIR-BI-mediated lipid transfer in intact cells. We identified five compounds that in the low nanomolar to micromolar range block lipid transport (BLTs), both selective uptake and efflux. The effects of these compounds were highly specific to the SR-BI pathway, because they didn't interfere with receptor-mediated endocytosis or with other forms of intracellular vesicular traffic. Surprisingly, all five BLTs enhanced, rather than inhibited, HDL binding by increasing SR-BI's binding affinity for HDL (decreased dissociation rates). Thus, the BLTs provide strong evidence for a mechanistic coupling between HDL binding and lipid transport and may serve as a starting point for the development of pharmacologically useful modifiers of SR-BI activity and, thus, HDL metabolism. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Krieger, M (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL52212, HL64737, HL66105, P01 HL066105, R01 HL052212, R01 HL064737]; NIGMS NIH HHS [GM62566, P01 GM062566] NR 36 TC 142 Z9 142 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 2002 VL 99 IS 24 BP 15422 EP 15427 DI 10.1073/pnas.222421399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000033 PM 12438696 ER PT J AU Chen, CZ Li, M de Graaf, D Monti, S Gottgens, B Sanchez, MJ Lander, ES Golub, TR Green, AR Lodish, HF AF Chen, CZ Li, M de Graaf, D Monti, S Gottgens, B Sanchez, MJ Lander, ES Golub, TR Green, AR Lodish, HF TI Identification of endoglin as a functional marker that defines long-term repopulating hematopoietic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BONE-MARROW; IN-VIVO; C-FOS; EXPRESSION; GENE; DIFFERENTIATION; PRECURSORS; PHENOTYPE; SUBSET; MOUSE AB We describe a strategy to obtain highly enriched long-term repopulating (LTR) hematopoietic stem cells (HSCs) from bone marrow side-population (SIP) cells by using a transgenic reporter gene driven by a stem cell enhancer. To analyze the gene-expression profile of the rare HSC population, we developed an amplification protocol termed "constant-ratio PCR," in which sample and control cDNAs are amplified in the same PCR. This protocol allowed us to identify genes differentially expressed in the enriched LTR-HSC population by oligonucleotide microarray analysis using as little as 1 mg of total RNA. Endoglin, an ancillary transforming growth factor 13 receptor, was differentially expressed by the enriched HSCs. Importantly, endoglin-positive cells, which account for 20% of total SIP cells, contain all the LTR-HSC activity within bone marrow SP. Our results demonstrate that endoglin, which plays important roles in angiogenesis and hematopoiesis, is a functional marker that defines LTR HSCs. Our overall strategy may be applicable for the identification of markers for other tissue-specific stem cells. C1 Nine Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 2XY, England. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02142 USA. RP Lodish, HF (reprint author), Nine Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RI Sanchez, Maria Jose/P-4716-2016; OI Sanchez, Maria Jose/0000-0003-3464-6224; Monti, Stefano/0000-0002-9376-0660; Gottgens, Berthold/0000-0001-6302-5705 NR 34 TC 105 Z9 113 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 2002 VL 99 IS 24 BP 15468 EP 15473 DI 10.1073/pnas.202614899 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000041 PM 12438646 ER PT J AU Harth, G Horwitz, MA Tabatadze, D Zamecnik, PC AF Harth, G Horwitz, MA Tabatadze, D Zamecnik, PC TI Targeting the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex as a therapeutic strategy against tuberculosis: Proof of principle by using antisense technology SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE phosphorothioate oligodeoxyribonucleotides mRNA secondary structure; inhibition of translation initiation; drug design ID PROTECTIVE IMMUNITY; IN-VIVO; OLIGONUCLEOTIDES; ANTIGEN; PROTEIN; OLIGODEOXYNUCLEOTIDES; PHOSPHOROTHIOATES; PURIFICATION; REPLICATION; INHIBITION AB We have investigated the effect of sequence-specific antisense phosphorothioate-modified oligodeoxyribonucleotides (PS-ODNs) targeting different regions of each of the 30/32-kDa protein complex (antigen 85 complex) encoding genes on the multiplication of Mycobacterium tuberculosis. Single PS-ODNs to one of the three mycolyl transferase transcripts, added either once or weekly over the 6-wk observation period, inhibited bacterial growth by up to 1 log unit. A combination of three PS-ODNs specifically targeting all three transcripts inhibited bacterial growth by approximate to2 logs; the addition of these PS-ODNs weekly for 6 wk was somewhat more effective than a one-time addition. Targeting the 5' end of the transcripts was more inhibitory than targeting internal sites; the most effective PS-ODNs and target sites had minimal or no secondary structure. The effect of the PS-ODNs was specific, as mismatched PS-ODNs had little or no inhibitory activity. The antisense PS-ODNs, which were highly stable in M. tuberculosis cultures, specifically blocked protein expression by their gene target. PS-ODNs targeting the transcript of a related 24-kDa protein (mpt51) had little inhibitory effect by themselves and did not increase the effect of PS-ODNs against the three members of the 30/32-kDa protein complex. The addition of PS-ODNs against the transcripts of glutamine synthetase I (glnA1) and alanine racemase (alr) modestly increased the inhibitory efficacy of the 30/32-kDa protein complex-specific PS-ODNs to approximate to2.5 logs. This study shows that the three mycolyl transferases are highly promising targets for antituberculous therapy by using antisense or other antimicrobial technologies. C1 Univ Calif Los Angeles, Sch Med, Ctr Hlth Sci 37 121, Dept Med,Div Infect Dis, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Horwitz, MA (reprint author), Univ Calif Los Angeles, Sch Med, Ctr Hlth Sci 37 121, Dept Med,Div Infect Dis, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NIAID NIH HHS [AI 42925] NR 20 TC 52 Z9 58 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 2002 VL 99 IS 24 BP 15614 EP 15619 DI 10.1073/pnas.242612299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000066 PM 12427974 ER PT J AU Mylonakis, E Ausubel, FM Perfect, JR Heitman, J Calderwood, SB AF Mylonakis, E Ausubel, FM Perfect, JR Heitman, J Calderwood, SB TI Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; AERUGINOSA VIRULENCE FACTORS; PSEUDOMONAS-AERUGINOSA; SALMONELLA-TYPHIMURIUM; FUNGAL DEVELOPMENT; GENE; HOST; PROTEIN; TRANSFORMATION; ASPERGILLOSIS AB We found that the well-studied nematode Caenorhabditis elegans can use various yeasts, including Cryptococcus laurentii and Cryptococcus kuetzingii, as a sole source of food, producing similar brood sizes compared with growth on its usual laboratory food source Escherichia coli OP50. C elegans grown on these yeasts had a life span similar to (C laurentii) or longer than (C kuetzingii) those fed on E. coli. However, the human pathogenic yeast Cryptococcus neoformans killed C elegans, and the C neoformans polysaccharide capsule as well as several C neoformans genes previously shown to be involved in mammalian virulence were also shown to play a role in C elegans killing. These included genes associated with signal transduction pathways (GPA1, PKA1, PKR1, and RAP), laccase production (LAC1), and the alpha mating type. C neoformans adenine auxotrophs, which are less virulent in mammals, were also less virulent in C elegans. These results support the model that mammalian pathogenesis of C neoformans may be a consequence of adaptations that have evolved during the interaction of C neoformans with environmental predators such as free-living nematodes and amoebae and suggest that C elegans can be used as a simple model host in which C neoformans pathogenesis can be readily studied. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Duke Univ, Med Ctr, Div Infect Dis, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. NR 65 TC 177 Z9 185 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 NOV 26 PY 2002 VL 99 IS 24 BP 15675 EP 15680 DI 10.1073/pnas.232568599 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000076 PM 12438649 ER PT J AU Schackman, BR Freedberg, KA Weinstein, MC Losina, E Zhang, H Goldie, S AF Schackman, BR Freedberg, KA Weinstein, MC Losina, E Zhang, H Goldie, S TI Cost-effectiveness implications of the timing of antiretroviral therapy in HIV-infected adults SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEASE INHIBITORS; METABOLIC ABNORMALITIES; CARDIOVASCULAR-DISEASE; FAT DISTRIBUTION; PLUS INDINAVIR; IMPACT; LIPODYSTROPHY; MANAGEMENT; RESISTANCE AB Background: The appropriate time to initiate antiretroviral therapy is controversial for human immunodeficiency virus (HIV)-infected patients with CD4 cell counts between 200/muL and 350/muL and low levels of HIV RNA, potentially leading to barriers to treatment access. Objective: To examine the effect of cholesterol changes and fat redistribution symptoms on the clinical benefits and cost-effectiveness of early antiretroviral therapy in these patients. Methods: We used a state-transition model to compare initiating antiretroviral therapy at CD4 cell counts of 350/muL (early therapy) with initiating therapy at CD4 cell counts of 200/muL (deferred therapy) in patients with HIV RNA levels of 10000 to 30000 copies/mL. Data were from randomized clinical trials, cohort studies, and other published literature. Results: If cholesterol changes associated with antiretroviral therapy resulted in a permanent increase in coronary heart disease risk, life expectancy with early therapy was 16.54 years (vs 16.66 years without this risk) and with deferred therapy was 13.73 years (vs 13.80 years without this risk). Early therapy was a more efficient use of resources (ie, dominated) compared with deferred therapy. Early therapy cost $13000 per quality-adjusted life-year compared with no therapy with or without increased coronary heart disease risk, and $17000 to $24000 per quality-adjusted life-year taking into account the quality-of-life reduction in patients with fat distribution symptoms. Early therapy had a higher quality-adjusted life expectancy than deferred therapy as long as this quality-of-life reduction was 70% or less. Conclusions: Changes in cholesterol or quality of life associated with antiretroviral therapy do not justify limiting access to early HIV treatment. The effect of fat redistribution symptoms on quality of life will determine the optimal choice of early vs deferred therapy for an individual patient. C1 Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. RP Schackman, BR (reprint author), Cornell Univ, Weill Med Coll, Dept Publ Hlth, Div Outcomes & Effectiveness Res, 411 E 69th St, New York, NY 10021 USA. FU NIAID NIH HHS [P30 AI42851, P30 AI042851, R01 AI042006, R01 AI42006]; NLM NIH HHS [LM07092-07, T15 LM007092]; ODCDC CDC HHS [U64/CCU119525, U64/CCU114927] NR 65 TC 54 Z9 55 U1 0 U2 0 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 NOV 25 PY 2002 VL 162 IS 21 BP 2478 EP 2486 DI 10.1001/archinte.162.21.2478 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 619HZ UT WOS:000179471700012 PM 12437408 ER PT J AU Mukherjee, S AF Mukherjee, S TI Resident aliens - Are medical residents working too hard? SO NEW REPUBLIC LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mukherjee, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW REPUBLIC INC PI WASHINGTON PA 1220 19TH ST NW SUITE 600, WASHINGTON, DC 20036 USA SN 0028-6583 J9 NEW REPUBLIC JI New Repub. PD NOV 25 PY 2002 VL 227 IS 22 BP 14 EP 18 PG 5 WC Political Science SC Government & Law GA 617GW UT WOS:000179354800011 ER PT J AU Mann, MA Tyler, KL Knipe, DM Fields, BN AF Mann, MA Tyler, KL Knipe, DM Fields, BN TI Type 3 reovirus neuroinvasion after intramuscular inoculation: Viral genetic determinants of lethality and spinal cord infection SO VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MOLECULAR-BASIS; MAMMALIAN REOVIRUSES; SIGMA-1 PROTEIN; M1 GENE; VIRULENCE; GROWTH; MICE; PATHOGENESIS; PARTICLES AB To better understand the mechanisms by which neurotropic viruses invade peripheral nerve pathways and produce CNS disease, we defined the type 3 (T3) reovirus genes that are determinants of the capacity of reovirus T3 strain Dearing (T3D) and T3 clone 9 (C9) to infect the spinal cord and kill mice after hindlimb injection. T3D and C9 viruses are both highly virulent (LD50 < 10(1) PFU) after intracranial injection of neonatal mice. However, C9 is significantly more lethal than T3D after either intramuscular injection (LD50 < 10(1) vs LD50 10(4) PFU) or peroral injection (LD50 10(3.4) vs LD50 > 10(8.3) PFU). Using reassortant viruses containing different combinations of genes derived from T3D and C9, we found that the S1 gene, encoding the cell attachment protein sigma 1 and the nonstructural protein sigma 1 s, and the L3 gene, encoding the core shell protein lambda 1 were the primary determinants of lethality after intramuscular injection. The L3 gene and the L2 gene encoding spike protein, lambda 2, determined differences in spinal cord titer after intramuscular injection. A C9 x T3D mono-reassortant containing all T3D genes except for the C9-derived L3 was lethal after peroral injection. These studies indicate that the S1, L2, and L3 genes all play a potential role in neuroinvasiveness and provide the first identification of a role in pathogenesis for the L3 gene. (C) 2002 Elsevier Science (USA). C1 Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Denver VA Med Ctr, Neurol Serv, Denver, CO 80262 USA. RP Mann, MA (reprint author), Columbia Univ Coll Phys & Surg, 630 W 168th St,11-519, New York, NY 10032 USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NINDS NIH HHS [P50 NS16998, P01 NS35138] NR 37 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 2002 VL 303 IS 2 BP 213 EP 221 DI 10.1006/viro.2002.1698 PG 9 WC Virology SC Virology GA 628GL UT WOS:000179984700001 PM 12490384 ER PT J AU Larsen, JE Sjostrom, H Noren, O Vogel, LK AF Larsen, JE Sjostrom, H Noren, O Vogel, LK TI Serpins are apically secreted from MDCK cells independently of their raft association SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Madin-Darby canine kidney cells; rafts; serpins; apical targeting ID DARBY CANINE KIDNEY; INFLUENZA-VIRUS HEMAGGLUTININ; GPI-ANCHORED PROTEINS; TRANS-GOLGI NETWORK; EPITHELIAL-CELLS; TRANSMEMBRANE DOMAIN; PLASMA-MEMBRANE; SORTING SIGNAL; N-GLYCANS; CHOLESTEROL DEPLETION AB It has been suggested that detergent-resistant membranes (DRMs), also known as lipid rafts, are involved in vectorial transport of proteins to the apical surface. In this report we use Madin-Darby canine kidney (MDCK) cells expressing the apically secreted Cl-esterase inhibitor, the non-sorted antithrombin or chimeras of serpins to study the possible connection between DRM association and apical targeting of secretory proteins. We found newly synthesised C1-esterase inhibitor associated with DRMs in MDCK cells, whereas antithrombin was not. However, two chimeric proteins, secreted mainly from the apical membrane, do not associate with DRMs. Based on these observations we suggest that apical targeting and association with DRMs are two independent events for secretory serpins. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Copenhagen, Panum Inst, Dept Med Biochem & Genet, Biochem Lab C, DK-2200 Copenhagen, Denmark. RP Larsen, JE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 47 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 22 PY 2002 VL 299 IS 1 BP 35 EP 41 AR PII S0006-291X(02)02577-9 DI 10.1016/S0006-291X(02)02577-9 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 619UW UT WOS:000179496700007 PM 12435386 ER PT J AU Maynard, CJ Cappai, R Volitakis, I Cherny, RA White, AR Beyreuther, K Masters, CL Bush, AI Li, QX AF Maynard, CJ Cappai, R Volitakis, I Cherny, RA White, AR Beyreuther, K Masters, CL Bush, AI Li, QX TI Overexpression of Alzheimer's disease amyloid-beta opposes the age-dependent elevations of brain copper and iron SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID A-BETA; TRANSGENIC MICE; TRACE-ELEMENTS; PRECURSOR PROTEIN; OXIDATIVE STRESS; CEREBROSPINAL-FLUID; CATALYZED OXIDATION; BINDING-SITE; SERUM ZINC; CONSEQUENCES AB Increased brain metal levels have been associated with normal aging and a variety of diseases, including Alzheimer's disease (AD). Copper and iron levels both show marked increases with age and may adversely interact with the amyloid-beta (Abeta) peptide causing its aggregation and the production of neurotoxic hydrogen peroxide (H2O2), contributing to the pathogenesis of AD. Amyloid precursor protein (APP) possesses copper/zinc binding sites in its amino-terminal domain and in the Abeta domain. Here we demonstrate that overexpression of the carboxyl-terminal fragment of APP, containing Abeta, results in significantly reduced copper and iron levels in transgenic mouse brain, while overexpression of the APP in Tg2576 transgenic mice results in significantly reduced copper, but not iron, levels prior to the appearance of amyloid neuropathology and throughout the lifespan of the mouse. Concomitant increases in brain manganese levels were observed with both transgenic strains. These findings, complemented by our previous findings of elevated copper levels in APP knock-out mice, support roles for APP and Abeta in physiological metal regulation. C1 Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Univ Heidelberg, Zentrum Mol Biol Heidelberg, D-69120 Heidelberg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Oxidat Biol Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Li, QX (reprint author), Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. RI Bush, Ashley/A-1186-2007; White, Anthony/P-5596-2016; OI Bush, Ashley/0000-0001-8259-9069; White, Anthony/0000-0003-1802-9891; Volitakis, Irene/0000-0003-0766-817X FU NIA NIH HHS [R01AG12656] NR 59 TC 233 Z9 240 U1 1 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 2002 VL 277 IS 47 BP 44670 EP 44676 DI 10.1074/jbc.M204379200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 618EE UT WOS:000179404800011 PM 12215434 ER PT J AU St-Pierre, J Buckingham, JA Roebuck, SJ Brand, MD AF St-Pierre, J Buckingham, JA Roebuck, SJ Brand, MD TI Topology of superoxide production from different sites in the mitochondrial electron transport chain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FREE-RADICAL PRODUCTION; HEART-MITOCHONDRIA; HYDROGEN-PEROXIDE; COMPLEX-I; UBIQUINONE OXIDOREDUCTASE; TRANSFER FLAVOPROTEIN; RESPIRATORY-CHAIN; GENERATION; OXYGEN; RAT AB We measured production of reactive oxygen species by intact mitochondria from rat skeletal muscle, heart, and liver under various experimental conditions. By using different substrates and inhibitors, we determined the sites of production (which complexes in the electron transport chain produced superoxide). By measuring hydrogen peroxide production in the absence and presence of exogenous superoxide dismutase, we established the topology of superoxide production (on which side of the mitochondrial inner membrane superoxide was produced). Mitochondria did not release measurable amounts of superoxide or hydrogen peroxide when respiring on complex I or complex II substrates. Mitochondria from skeletal muscle or heart generated significant amounts of superoxide from complex I when respiring on palmitoyl carnitine. They produced superoxide at considerable rates in the presence of various inhibitors of the electron transport chain. Complex I (and perhaps the fatty acid oxidation electron transfer flavoprotein and its oxidoreductase) released superoxide on the matrix side of the inner membrane, whereas center o of complex III released superoxide on the cytoplasmic side. These results do not support the idea that mitochondria produce considerable amounts of reactive oxygen species under physiological conditions. Our upper estimate of the proportion of electron flow giving rise to hydrogen peroxide with palmitoyl carnitine as substrate (0.15%) is more than an order of magnitude lower than commonly cited values. We observed no difference in the rate of hydrogen peroxide production between rat and pigeon heart mitochondria respiring on complex I substrates. However, when complex I was fully reduced using rotenone, rat mitochondria released significantly more hydrogen peroxide than pigeon mitochondria. This difference was solely due to an elevated concentration of complex I in rat compared with pigeon heart mitochondria. C1 MRC Dunn Human Nutr Unit, Cambridge CB2 2XY, England. RP St-Pierre, J (reprint author), Dana Farber Canc Inst, SM 958, Boston, MA 02115 USA. RI Brand, Martin/A-9423-2012 OI Brand, Martin/0000-0003-4418-6153 NR 37 TC 837 Z9 881 U1 7 U2 51 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 2002 VL 277 IS 47 BP 44784 EP 44790 DI 10.1074/jbc.M207217200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 618EE UT WOS:000179404800027 PM 12237311 ER PT J AU Rogers, JT Randall, JD Cahill, CM Eder, PS Huang, XD Gunshin, H Leiter, L McPhee, J Sarang, SS Utsuki, T Greig, NH Lahiri, DK Tanzi, RE Bush, AI Giordano, T Gullans, SR AF Rogers, JT Randall, JD Cahill, CM Eder, PS Huang, XD Gunshin, H Leiter, L McPhee, J Sarang, SS Utsuki, T Greig, NH Lahiri, DK Tanzi, RE Bush, AI Giordano, T Gullans, SR TI An iron-responsive element type II in the 5 '-untranslated region of the Alzheimer's amyloid precursor protein transcript SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; BETA-PROTEIN; REGULATORY PROTEINS; BINDING PROTEIN; DISEASE; FERRITIN; TRANSLATION; GENE; INTERLEUKIN-1; RECEPTOR AB Iron-responsive elements (IREs) are the RNA stem loops that control cellular iron homeostasis by regulating ferritin translation and transferrin receptor mRNA stability. We mapped a novel iron-responsive element (IRE-Type II) within the 5'-untranslated region (5'-UTR) of the Alzheimer's amyloid precursor protein (APP) transcript (+51 to +94 from the 5'-cap site). The APP mRNA IRE is located immediately upstream of an interleukin-1 responsive acute box domain (+101 to +146). APP 5'-UTR conferred translation was selectively down-regulated in response to intracellular iron chelation using three separate reporter assays (chloramphenicol acetyltransferase, luciferase, and red fluorescent protein reflecting an inhibition of APP holoprotein translation in response to iron chelation. Iron influx reversed this inhibition. As an internal control to ensure specificity, a viral internal ribosome entry sequence was unresponsive to intracellular iron chelation with desferrioxamine. Using RNA mobility shift assays, the APP 5'-UTRs, encompassing the IRE, bind specifically to recombinant iron-regulatory proteins (IRP) and to IRP from neuroblastoma cell lysates. IRP binding to the APP 5'-UTR is reduced after treatment of cells with desferrioxamine and increased after interleukin-1 stimulation. IRP binding is abrogated when APP cRNA probe is mutated in the core IRE domain (Delta4 bases:Delta83AGAG86). Iron regulation of APP mRNA through the APP 5'-UTR points to a role for iron in the metabolism of APP and confirms that this RNA structure can be a target for the selection of small molecule drugs, such as desferrioxamine We chelator) and clioquinol (Fe, Cu, and Zn chelator), which reduce Abeta peptide burden during Alzheimer's disease. C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Diabet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Charlestown, MA 02129 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. Message Pharmaceut, Malvern, PA 19355 USA. RP Rogers, JT (reprint author), Harvard Univ, Sch Med, Genet & Aging Res Unit, Dept Psychiat Neurosci, Mass Gen E,Bldg 114,3850 16th St, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIMH NIH HHS [5K01MH02001] NR 49 TC 297 Z9 308 U1 2 U2 19 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 2002 VL 277 IS 47 BP 45518 EP 45528 DI 10.1074/jbc.M207435200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 618EE UT WOS:000179404800117 PM 12198135 ER PT J AU Fisher, CM AF Fisher, CM TI Perspective: Transient ischemic attacks SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 23 Z9 23 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 21 PY 2002 VL 347 IS 21 BP 1642 EP 1643 DI 10.1056/NEJMp020129 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 617BL UT WOS:000179339900001 PM 12444177 ER PT J AU van Walraven, C Hart, RG Singer, DE Laupacis, A Connolly, S Petersen, P Koudstaal, PJ Chang, YC Hellemons, B AF van Walraven, C Hart, RG Singer, DE Laupacis, A Connolly, S Petersen, P Koudstaal, PJ Chang, YC Hellemons, B TI Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation - An individual patient meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FIXED MINIDOSE WARFARIN; STROKE PREVENTION; ANTITHROMBOTIC THERAPY; SECONDARY PREVENTION; METAANALYSIS; TRIALS; THROMBOEMBOLISM AB Context Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke and other vascular events. Objective To compare the risk of vascular and bleeding events in patients with nonvalvular AF treated with vitamin K-inhibiting oral anticoagulants or acetylsalicylic acid (aspirin). Design Pooled analysis of patient-level data from 6 published, randomized clinical trials. Patients A total of 4052 patients with AF randomly assigned to receive therapeutic doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants. Main Outcome Measures Ischemic and hemorrhagic stroke, other cardiovascular events, all-cause death, and major bleeding events. Person-year incidence rates were calculated to provide crude comparisons. Relative efficacy was assessed using proportional hazards modeling stratified by study. The variation of the oral anticoagulant's relative effect by pertinent patient factors was explored with interaction terms. All analyses were conducted using the intention-to-treat principle. Results Patients receiving oral anticoagulant and aspirin were balanced for important prognostic factors. There was no significant heterogeneity between trials in the relative efficacy of oral anticoagulant vs aspirin for any outcome. Patients receiving oral anticoagulant were significantly less likely to experience any stroke (2.4 vs 4.5 events per 100 patient-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71), ischemic stroke (HR, 0.48; 95% CI, 0.37-0.63), or cardiovascular events (HR, 0.71; 95% CI, 0.59-0.85) but were more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient-years; HR, 1.71; 95% CI, 1.21-2.41). The reduction in ischemic stroke risk was similar in patients with paroxysmal AF (1.5 vs 4.7 events per 100 patient-years; HR, 0.32; 95% CI, 0.16-0.61; P<.001). Treating 1000 patients with AF for 1 year with oral anticoagulant rather than aspirin would prevent 23 ischemic strokes while causing 9 additional major bleeds. Overall all-cause survival did not differ but appeared to improve for oral anticoagulant patients 3 years after therapy was started. Conclusions Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk of major bleeding. The balance of benefits and risks varies by patient subgroup. C1 Ottawa Hlth Res Inst, Clin Epidemiol Unit, Ottawa, ON, Canada. Inst Clin Evaluat Sci, Ottawa, ON, Canada. Canadian Inst Hlth Res, Ottawa, ON, Canada. Univ Texas, Dept Med, San Antonio, TX 78285 USA. Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. McMaster Univ, Hamilton, ON, Canada. Hvidovre Univ Hosp, Copenhagen, Denmark. Erasmus MC, Dept Neurol, Rotterdam, Netherlands. Univ Maastricht, Maastricht, Netherlands. RP van Walraven, C (reprint author), Ottawa Civic Hosp, Ottawa Hlth Res Inst, Clin Epidemiol Unit, F-6,1053 Carling Ave, Ottawa, ON K1Y 4E9, Canada. NR 58 TC 378 Z9 386 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 20 PY 2002 VL 288 IS 19 BP 2441 EP 2448 DI 10.1001/jama.288.19.2441 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 616FB UT WOS:000179292300027 PM 12435257 ER PT J AU Sabatine, MS Morrow, DA Cannon, CP Murphy, SA Demopoulos, LA DiBattiste, PM McCabe, CH Braunwald, E Gibson, CM AF Sabatine, MS Morrow, DA Cannon, CP Murphy, SA Demopoulos, LA DiBattiste, PM McCabe, CH Braunwald, E Gibson, CM TI Relationship between baseline white blood cell count and degree of coronary artery disease and mortality in patients with acute coronary syndromes - A TACTICS-TIMI 18 substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 51st Annual Scientific Session of the American-College-of-Cardiology CY MAR 17-20, 2002 CL ATLANTA, GEORGIA SP Amer Coll Cardiol ID ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; UNSTABLE ANGINA; TROPONIN-T; RANDOMIZED TRIAL; THROMBOLYSIS; INFLAMMATION; ASSOCIATION; REPERFUSION; EXPRESSION AB OBJECTIVES This study, was designed to determine the relationship between baseline white blood cell (WBC) count and angiographic and clinical outcomes in patients with unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) and to see if WBC count was a significant predictor of outcomes independent of other biomarkers. BACKGROUND Inflammation has been shown to play a role in atherosclerosis and acute coronary syndromes. METHODS We evaluated the relationship between baseline WBC count, other baseline variables and biomarkers, angiographic findings, and clinical outcomes in 2,208 patients in the Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18 (TACTICS-TIMI 18) trial. RESULTS Higher baseline WBC counts were associated with lower Thrombolysis In Myocardial Infarction (TIMI) flow grades (p = 0.0045) and TIMI myocardial perfusion grades (p = 0.03) as well as a greater extent of coronary artery disease (CAD) (p < 0.0001). A higher baseline WBC count was predictive of higher six-month mortality, ranging from 1.5% to 3.6% to 5.1% for patients with low, intermediate, and high WBC counts, respectively (p = 0.0017). In a multivariable proportional hazards model, patients with a low C-reactive protein (CRP) but an elevated WBC remained at significantly higher risk of death at six months (hazard ratio [HR] 4.3, p = 0.049), and patients with a high CRP were at even higher risk (HR 8.6, p = 0.004). CONCLUSIONS In patients with UA/NSTEMI, elevations in a simple, widely available blood test, the WBC count, were associated with impaired epicardial and myocardial perfusion, more extensive CAD, and higher six-month mortality. After adjustment. for traditional risk factors and other biomarkers, assessment of two inflammatory markers, WBC count and CRP, can be used to stratify patients across an eightfold gradation of six-month mortality risk. (C) 2002 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Clin Res Inst, Boston, MA 02115 USA. Merck & Co Inc, W Point, PA USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [F32 HL 68455-01] NR 29 TC 148 Z9 156 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 20 PY 2002 VL 40 IS 10 BP 1761 EP 1768 AR PII S0735-1097(02)02484-1 DI 10.1016/S0735-1097(02)02484-1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 616MY UT WOS:000179308600007 PM 12446059 ER PT J AU Rumsfeld, JS Plomondon, ME Peterson, ED Shlipak, MG Maynard, C Grunwald, GK Grover, FL Shroyer, ALW AF Rumsfeld, JS Plomondon, ME Peterson, ED Shlipak, MG Maynard, C Grunwald, GK Grover, FL Shroyer, ALW TI The impact of ethnicity on outcomes following coronary artery bypass graft surgery in the Veterans Health Administration SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; ACUTE MYOCARDIAL-INFARCTION; INVASIVE CARDIAC PROCEDURES; RACIAL-DIFFERENCES; REVASCULARIZATION PROCEDURES; OPERATIVE MORTALITY; CARDIOVASCULAR PROCEDURES; AFFAIRS; RACE; IDENTIFICATION AB OBJECTIVES We evaluated the effect of African American (AA) and Hispanic American (HA) ethnicity on mortality and complications following coronary artery bypass graft (CABG) surgery in the Veterans Health Administration (VHA). BACKGROUND Few studies have examined the impact of ethnicity on outcomes following cardiovascular procedures. METHODS This study included all 29,333 Caucasian, 2,570 AA, and 1,525 HA patients who underwent CABG surgery at any one of the 43 VHA cardiac surgery centers from January 1995 through March 2001. We evaluated the relationship between ethnicity, (AA vs. Caucasian and HA vs. Caucasian) and 30-day mortality, 6-month mortality, and 30-day complications, adjusting for a wide array of demographic, cardiac, and noncardiac variables. RESULTS After adjustment for baseline characteristics, AA and Caucasian patients had similar 30-day (AA/Caucasian odds ratio [OR] 1.07; 95% confidence interval [CI] 0,84 to 1.35; p = 0.59) and 6-month mortality, risk (AA/Caucasian OR 1.10; 95% CI 0.91 to 1.34; p = 0.31). However, among patients with low surgical risk, AA ethnicity was associated with higher mortality (OR 1.52, CI 1.10 to 2.11, p = 0.01), and AA patients were more likely to experience complications following surgery (OR 1.28; 95% CI 1.14 to 1.45; p < 0.01). In contrast, HA patients had lower 30-day (HA/Caucasian OR 0.70; 95% CI 0.49 to 0.98; p = 0.04) and 6-month mortality risk (HA/Caucasian OR 0.66; 95% CI 0.50 to 0.88; p < 0.01) than Caucasian patients. CONCLUSIONS Ethnicity does not appear to be a strong risk factor for adverse outcomes following CABG surgery in the VHA. Future studies are needed to determine why AA patients have more complications, but ethnicity should not affect the decision to offer the operation. (C) 2002 by the American College of Cardiology Foundation. C1 Vet Adm Med Ctr, Denver, CO USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Duke Univ, Durham, NC 27706 USA. RP Rumsfeld, JS (reprint author), Vet Adm Med Ctr, Cardiol 111B,1055 Clermont St, Denver, CO USA. RI Shroyer, Annie Laurie/B-8836-2016; Maynard, Charles/N-3906-2015 OI Shroyer, Annie Laurie/0000-0001-6461-0623; Maynard, Charles/0000-0002-1644-7814 NR 43 TC 20 Z9 21 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 20 PY 2002 VL 40 IS 10 BP 1786 EP 1793 AR PII S0735-1097(02)02485-3 DI 10.1016/S0735-1097(02)02485-3 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 616MY UT WOS:000179308600010 PM 12446062 ER PT J AU Chen, WY Colditz, GA Rosner, B Hankinson, SE Hunter, DJ Manson, JE Stampfer, MJ Willett, WC Speizer, FE AF Chen, WY Colditz, GA Rosner, B Hankinson, SE Hunter, DJ Manson, JE Stampfer, MJ Willett, WC Speizer, FE TI Use of postmenopausal hormones, alcohol, and risk for invasive breast cancer SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID REPLACEMENT THERAPY; BEVERAGE CONSUMPTION; MEASUREMENT ERROR; WOMEN; ESTROGENS; COHORT AB Background: Physiologic evidence suggests that use of alcohol increases the risk for breast cancer through a hormonal mechanism, but the relationship among breast cancer, alcohol, and postmenopausal hormones (PMH) remains unclear. Objective: To examine the relation between concurrent use of alcohol and PMH and invasive breast cancer. Design: Prospective cohort study Setting: Nurses' Health Study. Participants: 44187 postmenopausal women. Measurements: Self-reported data on PMH use and breast cancer obtained from biennial questionnaires completed from 1980 to 1994 and average alcohol consumption in 1980, 1984, 1986, and 1990. Results: 1722 women developed invasive breast cancer. Risk for breast cancer was elevated in women who currently used PMH for 5 or more years and did not drink alcohol (relative risk, 1.32 [95% CI, 1.05 to 1.66]) and those who never used PMH but drank 20 or more g (1.5 to 2 drinks) of alcohol daily (relative risk, 1.28 [Cl, 0.97 to 1.69]). Current users of PMH for 5 or more years who consumed 20 or more g of alcohol daily had a relative risk for breast cancer nearly twice (1.99 [Cl, 1.42 to 2.79]) that of non-drinking nonusers of PMH. A hypothetical postmenopausal woman whose lifetime risk for breast cancer is 4% could increase her risk to 8% with 5 or more years of current PMH use and consumption of more than one alcoholic drink daily. Conclusions: Both alcohol consumption and PMH use were associated with an increased incidence of breast cancer. Women who are currently taking PMH may want to consider the added risks of regular alcohol consumption. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chen, WY (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356, 5-R25-CA577011-08] NR 28 TC 55 Z9 55 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 NOV 19 PY 2002 VL 137 IS 10 BP 798 EP 804 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 616VE UT WOS:000179323400003 PM 12435216 ER PT J AU Garg, HG Cindhuchao, N Quinn, DA Hales, CA Thanawiroon, C Capila, I Linhardt, RJ AF Garg, HG Cindhuchao, N Quinn, DA Hales, CA Thanawiroon, C Capila, I Linhardt, RJ TI Heparin oligosaccharide sequence and size essential for inhibition of pulmonary artery smooth muscle cell proliferation SO CARBOHYDRATE RESEARCH LA English DT Article DE heparin; smooth muscle cells (SMCs); oligosaccharide ID STRUCTURAL DETERMINANTS; ANTIPROLIFERATIVE ACTIVITY; MOLECULAR-WEIGHT; SULFATE; GLYCOSAMINOGLYCANS; ELECTROPHORESIS; ANTICOAGULANT; HYPERTENSION; SEPARATION; CAPACITY AB Heparin has a wide range of important biological activities including inhibition of pulmonary artery smooth muscle cell proliferation. To determine the minimum size of the heparin glycosaminoglycan chain essential for antiproliferative activity, porcine intestinal mucosal heparin was partially depolymerized with heparinase and fractionated to give oligosaccharides of different sizes. The structure of these oligosaccharides was fully characterized by ID and 2D H-1 NMR spectroscopy. These oligosaccharides were assayed for antiproliferative effects on cultured bovine pulmonary artery smooth muscle cells (PASMCs). The tetrasaccharide (4-mer) exhibited no heparin-like activity. Decasaccharides (10-mers) and dodecasaccharides (12-mers) displayed a reduced level of activity when compared to full-length heparin. Little effect on activity was observed in deca- and dodecasaccharides with one less 2-O-sulfo group. The 14-, 16-, and 18-mers showed comparable growth-inhibition effects on PAMSC as porcine intestinal mucosal heparin. These data suggest that a 14-mer is the minimum size of oligosaccharide that is essential for full heparin-like antiproliferative activity. Since the 14- to 18-mers have no 3-O-sulfo groups in their glucosamine residues, their full activity confirms that these 3-O-sulfonated glucosamine residues, which are required for heparin's anticoagulant activity, are not an essential requirement for antiproliferative activity. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Pulm Crit Care Unit, Boston, MA 02114 USA. Univ Iowa, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. Univ Iowa, Dept Chem & Biochem Engn, Iowa City, IA 52242 USA. RP Garg, HG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Pulm Crit Care Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL52622, HL 03220, HL 39150, R01 HL039150]; NIGMS NIH HHS [GM38060] NR 33 TC 8 Z9 14 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 19 PY 2002 VL 337 IS 21-23 BP 2359 EP 2364 AR PII S0008-6215(02)00190-8 DI 10.1016/S0008-6215(02)00190-8 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 618PB UT WOS:000179425500047 PM 12433502 ER PT J AU Szabo, C Zanchi, A Komjati, K Pacher, P Krolewski, AS Quist, WC LoGerfo, FW Horton, ES Veves, A AF Szabo, C Zanchi, A Komjati, K Pacher, P Krolewski, AS Quist, WC LoGerfo, FW Horton, ES Veves, A TI Poly(ADP-ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity SO CIRCULATION LA English DT Article DE diabetes mellitus; endothelium; acetylcholine; microcirculation ID NITRIC-OXIDE SYNTHASE; CORONARY-ARTERY DISEASE; ENDOTHELIAL DYSFUNCTION; MOLECULAR MECHANISMS; INSULIN-RESISTANCE; IN-VIVO; PEROXYNITRITE; GENE; EXPRESSION; RECEPTOR AB Background-We have previously shown that endothelial function is impaired not only in diabetes but also in subjects at risk of developing type 2 diabetes. We hypothesized that changes in the expression or activity of the endothelial isoform of nitric oxide synthase (eNOS), the receptor for advanced glycation end products (RAGE), and poly(ADP-ribose) polymerase (PARP) are related to this impairment. Methods and Results-We included a control group of 21 healthy subjects, a group of 22 healthy individuals with parental history of type 2 diabetes, a group of 23 subjects with impaired glucose tolerance, and a group of 21 type 2 diabetic patients. Two 2-mm forearm skin biopsies were taken from each participant and used for measurements. The percentage of PARP-positive endothelial nuclei was higher in the group with parental history of type 2 diabetes and diabetic patients compared with the controls (P<0.001). Immunoreactivity for nitrotyrosine (a marker of reactive nitrogen species) was higher in the diabetic group compared with all other groups (P<0.01). No differences in the expression of eNOS and RAGE were found among all 4 groups. The polymorphism of the eNOS gene was also studied and was not found to influence eNOS expression or microvascular functional measurements. Conclusions-PARP activation is present in healthy subjects at risk of developing diabetes as well as in established type 2 diabetic patients, and it is associated with impairments in the vascular reactivity in the skin microcirculation. C1 Beth Israel Deaconess Med Ctr, Microcirculat Lab, Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Vasc Surg, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. Inotek Pharmaceut Corp, Beverly, MA USA. RP Veves, A (reprint author), Beth Israel Deaconess Med Ctr, Microcirculat Lab, Joslin Diabet Ctr, W Campus,1 Deaconess Rd, Boston, MA 02215 USA. RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU NCRR NIH HHS [RR 01032]; NHLBI NIH HHS [1R01HL/DK71215-01] NR 34 TC 124 Z9 126 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 19 PY 2002 VL 106 IS 21 BP 2680 EP 2686 DI 10.1161/01.CIR.0000038365.78031.9C PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 618LX UT WOS:000179420500012 PM 12438293 ER PT J AU Gupta, S Knowlton, AA AF Gupta, S Knowlton, AA TI Cytosolic heat shock protein 60, hypoxia, and apoptosis SO CIRCULATION LA English DT Article DE apoptosis; hypoxia; ischemia; myocytes ID CYTOCHROME-C RELEASE; DILATED CARDIOMYOPATHY; CELLS; BAX; REOXYGENATION; EXPRESSION; TRANSLOCATION; MITOCHONDRIA; LOCALIZATION; ACTIVATION AB Background-Heat shock protein (HSP)60 is an abundant protein found primarily in the mitochondria, though 15% to 20% is found in the cytosol. Previously we observed that HSP60 complexes with bax in the cytosol. Reduction in HSP60 precipitates translocation of bax to the mitochondria and apoptosis. We hypothesized that HSP60 would decrease with hypoxia/reoxygenation and that this would precipitate bax translocation to the mitochondria and release of cytochrome c. Methods and Results-Adult rat cardiac myocytes were studied at end-hypoxia and at 10 and 24 hours of reoxygenation. HSP60 levels were unchanged at end-hypoxia and decreased 33% and 40% at 10 and 24 hours of reoxygenation, whereas HSP72 increased 80% and 110%. Bax and bcl-2 decreased during reoxygenation. However, cytochrome c release occurred at end-hypoxia, before reoxygenation. Cell fractionation was done to analyze this further. In normal myocytes, bax and HSP60 were present in the cytosol, and bax coimmunoprecipitated with cytosolic HSP60. At end-hypoxia, mitochondrial HSP60 was unchanged, but cytosolic HSP60 had disappeared and was now in the plasma membrane fraction. Concurrently, bax was no longer in the cytosol but now in the mitochondria. Thus, although total HSP60 remained the same, it no longer complexed with bax, and bax was free to translocate to the mitochondria and precipitate apoptosis. Reduction in ATP had a similar effect. Conclusions-These studies show that hypoxia results in disassociation of the HSP60-bax complex with translocation of cytosolic HSP60 to the plasma membrane and bax to the mitochondria. This is sufficient to trigger apoptosis. C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. RP Univ Calif Davis, Div Cardiovasc, TB172,1 Shields Ave, Davis, CA 95616 USA. EM aaknowlton@ucdavis.edu FU NHLBI NIH HHS [HL58515, R01 HL058515]; NIA NIH HHS [R01 AG019327, AG19327] NR 27 TC 102 Z9 108 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 19 PY 2002 VL 106 IS 21 BP 2727 EP 2733 DI 10.1061/01.CIR.0000038112.64503.6E PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 618LX UT WOS:000179420500019 PM 12438300 ER PT J AU Hofmann, ER Milstein, S Boulton, SJ Ye, MJ Hofmann, JJ Stergiou, L Gartner, A Vidal, M Hengartner, MO AF Hofmann, ER Milstein, S Boulton, SJ Ye, MJ Hofmann, JJ Stergiou, L Gartner, A Vidal, M Hengartner, MO TI Caenorhabditis elegans HUS-1 is a DNA damage checkpoint protein required for genome stability and EGL-1-mediated apoptosis SO CURRENT BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; TUMOR-SUPPRESSOR P53; SCHIZOSACCHAROMYCES-POMBE; C. ELEGANS; SACCHAROMYCES-CEREVISIAE; GENETIC-CONTROL; S-PHASE; PATHWAYS; KINASE; REPLICATION AB Background: The inability to efficiently repair DNA damage or remove cells with severely damaged genomes has been linked to several human cancers. Studies in yeasts and mammals have identified several genes that are required for proper activation of cell cycle checkpoints following various types of DNA damage. However, in metazoans, DNA damage can induce apoptosis as well. How DNA damage activates the apoptotic machinery is not fully understood. Results: We demonstrate here that the Caenorhabditis elegans gene hus-1 is required for DNA damage-induced cell cycle arrest and apoptosis. Following DNA damage, HUS-1 relocalizes and forms distinct foci that overlap with chromatin. Relocalization does not require the novel checkpoint protein RAD-5; rather, relocalization appears more frequently in rad-5 mutants, suggesting that RAD-5 plays a role in repair. HUS-1 is required for genome stability, as demonstrated by increased frequency of spontaneous mutations, chromosome nondisjunction, and telomere shortening. Finally, we show that DNA damage increases expression of the proapoptotic gene egl-1, a response that requires hus-1 and the p53 homolog cep-1. Conclusions: Our findings suggest that the RAD-5 checkpoint protein is not required for HUS-1 to relocalize following DNA damage. Furthermore, our studies reveal a new function of HUS-1 in the prevention of telomere shortening and mortalization of germ cells. DNA damage-induced germ cell death is abrogated in hus-1 mutants, in part, due to the inability of these mutants to activate egl-1 transcription in a cep-1/p53dependent manner. Thus, HUS-1 is required for p53-dependent activation of a BH3 domain protein in C. elegans. C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Canc Res UK, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany. Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland. RP Hengartner, MO (reprint author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA. RI Hengartner, Michael/A-7058-2008; Hengartner, Michael/E-6235-2011; OI Hengartner, Michael/0000-0002-7584-596X; Gartner, Anton/0000-0003-4639-9902 FU NCI NIH HHS [7 R33 CA81658-02]; NIGMS NIH HHS [F32GM20801, GM52540] NR 47 TC 143 Z9 170 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 19 PY 2002 VL 12 IS 22 BP 1908 EP 1918 AR PII S0960-9822(02)01262-9 DI 10.1016/S0960-9822(02)01262-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 619QC UT WOS:000179486700017 PM 12445383 ER PT J AU Walhout, AJM Reboul, J Shtanko, O Bertin, N Vaglio, P Ge, H Lee, H Doucette-Stamm, L Gunsalus, KC Schetter, AJ Morton, DG Kemphues, KJ Reinke, V Kim, SK Piano, F Vidal, M AF Walhout, AJM Reboul, J Shtanko, O Bertin, N Vaglio, P Ge, H Lee, H Doucette-Stamm, L Gunsalus, KC Schetter, AJ Morton, DG Kemphues, KJ Reinke, V Kim, SK Piano, F Vidal, M TI Integrating interactome, phenome, and transcriptome mapping data for the C-elegans germline SO CURRENT BIOLOGY LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; GENOME; YEAST; SEQUENCE; SCALE; MAPS; RNA AB By integrating functional genomic and proteomic mapping approaches, biological hypotheses should be formulated with increasing levels of confidence [1-5]. For example, yeast interactome and transcriptome data can be correlated in biologically meaningful ways [69]. Here, we combine interactome mapping data generated for a multicellular organism with data from both large-scale phenotypic analysis ("phenome mapping") and transcriptome profiling. First, we generated a two-hybrid interactome map of the Caenorhabditis elegans germline by using 600 transcripts enriched in this tissue [10]. We compared this map to a phenome map of the germline obtained by RNA interference (RNAi) [34] and to a transcriptome map obtained by clustering worm genes across 553 expression profiling experiments [11]. In this dataset, we find that essential proteins have a tendency to interact with each other, that pairs of genes encoding interacting proteins tend to exhibit similar expression profiles, and that, for similar to24% of germline interactions, both partners show overlapping embryonic lethal or high incidence of males RNAi phenotypes and similar expression profiles. We propose that these interactions are most likely to be relevant to germline biology. Similar integration of interactome, phenome, and transcriptome data should be possible for other biological processes in the nematode and for other organisms, including humans. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Genome Therapeut, Waltham, MA 02154 USA. NYU, Dept Biol, New York, NY 10011 USA. Cornell Univ, Ithaca, NY 14850 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Stanford Univ, Dept Dev Biol & Genet, Stanford, CA 94305 USA. RP Vidal, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Bertin, Nicolas/C-3025-2008; Reboul, Jerome/P-9103-2016; OI Bertin, Nicolas/0000-0002-9835-9606; Reboul, Jerome/0000-0002-5513-4546; Walhout, Marian/0000-0001-5587-3608 FU NCI NIH HHS [7 R33 CA81658-02]; NHGRI NIH HHS [5R01HG01715-02] NR 34 TC 126 Z9 127 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 19 PY 2002 VL 12 IS 22 BP 1952 EP 1958 AR PII S0960-9822(02)01279-4 DI 10.1016/S0960-9822(02)01279-4 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 619QC UT WOS:000179486700024 PM 12445390 ER PT J AU Ortel, B Sharlin, D O'Donnell, D Sinha, AK Maytin, EV Hasan, T AF Ortel, B Sharlin, D O'Donnell, D Sinha, AK Maytin, EV Hasan, T TI Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE photodynamic therapy; retinoid; aminolevulinic acid; vitamin D; androgen ID TRANS-RETINOIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; PRIMARY MOUSE KERATINOCYTES; TERMINAL DIFFERENTIATION; 5-AMINOLEVULINIC ACID; INDUCED PROTOPORPHYRIN; VITAMIN-D-3 ANALOG; THERAPY; PHOTOTOXICITY; PROLIFERATION AB Photodynamic therapy using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) may be applied to the treatment of neoplasms in a variety of organs. In order to enhance existing regimens of photodynamic therapy, we investigated the effects of adding differentiation therapy to photodynamic therapy in human prostate cancer cells in vitro. The objective of differentiation therapy per se is to reverse the lack of differentiation in cancer cells using pharmacological agents. The motivation for this study was to exploit the differentiation-dependent expression of some heme enzymes to enhance tumour cell toxicity of ALA-photodynamic therapy. A short course of differentiation therapy was applied to increase PpIX formation during subsequent ALA exposure. Using the synthetic androgen R 188 1, isomers of retinoic acid, and analogues of vitamin D for 3 to 4 days, exogenous ALA-dependent PpIX formation in LNCaP cells was increased, along with marker's for growth arrest and for differentiation. As a consequence of higher PpIX levels, cytotoxic effects of visible light exposure were also enhanced. Short-term differentiation therapy increased not only the overall PpIX production but also reduced that fraction of cells that contained low PpIX levels as demonstrated by flow cytometry and fluorescence microscopy. This study suggests that it will be feasible to develop protocols combining short-term differentiation therapy with photodynamic therapy for enhanced photosensitisation. (C) 2002 Cancer Research UK. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Biomed Engn ND20, Lerner Res Inst, Cleveland, OH 44195 USA. RP Ortel, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, WEL-224,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [P01 CA084203, R01 CA156177, 1P01 CA84203-01] NR 27 TC 61 Z9 63 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 18 PY 2002 VL 87 IS 11 BP 1321 EP 1327 DI 10.1038/sj.bjc.6600575 PG 7 WC Oncology SC Oncology GA 625MH UT WOS:000179819900021 PM 12439724 ER PT J AU Feldhahn, N Schwering, I Lee, S Wartenberg, M Klein, F Wang, H Zhou, GL Wang, SM Rowley, JD Hescheler, J Kronke, M Rajewsky, K Kuppers, RK Muschen, M AF Feldhahn, N Schwering, I Lee, S Wartenberg, M Klein, F Wang, H Zhou, GL Wang, SM Rowley, JD Hescheler, J Kronke, M Rajewsky, K Kuppers, RK Muschen, M TI Silencing of B cell receptor signals in human naive B cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE B cell receptor; IL-4; ITIM; memory B cells; SAGE ID BRUTONS TYROSINE KINASE; MAJOR HISTOCOMPATIBILITY COMPLEX; NF-KAPPA-B; BINDING PROTEIN; T-CELLS; IMMUNOGLOBULIN SUPERFAMILY; ANTIBODY-PRODUCTION; TRANSGENIC MICE; GENE-EXPRESSION; ANTIGEN AB To identify changes in the regulation of B cell receptor (BCR) signals during the development of human B cells, we generated genome-wide gene expression profiles using the serial analysis of gene expression (SAGE) technique for CD34(+) hematopoietic stem cells (HSCs), pre-B cells, naive, germinal center (GC), and memory B cells. Comparing these SAGE profiles, genes encoding positive regulators of BCR signaling were expressed at consistently lower levels in naive B cells than in all other B cell subsets. Conversely, a large group of inhibitory signaling molecules, mostly belonging to the immunoglobulin superfamily (IgSF), were specifically or predominantly expressed in naive B cells. The quantitative differences observed by SAGE were corroborated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. In a functional assay, we show that down-regulation of inhibitory IgSF receptors and increased responsiveness to BCR stimulation in memory as compared with naive B cells at least partly results from interleukin (IL)-4 receptor signaling. Conversely, activation or impairment of the inhibitory IgSF receptor LIRB1 affected BCR-dependent Ca2+ mobilization only in naive but not memory B cells. Thus, LIRB1 and IL-4 may represent components of two nonoverlapping gene expression programs in naive and memory B cells, respectively: in naive B cells, a large group of inhibitory IgSF receptors can elevate the BCR signaling threshold to prevent these cells from premature activation and clonal expansion before GC-dependent affinity maturation. In memory B cells, facilitated responsiveness upon reencounter of the immunizing antigen may result from amplification of BCR signals at virtually all levels of signal transduction. C1 Univ Cologne, Inst Genet, Emmy Noether Grp, D-50931 Cologne, Germany. Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50931 Cologne, Germany. Univ Cologne, Inst Neurophysiol, D-50931 Cologne, Germany. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Muschen, M (reprint author), Univ Cologne, Inst Genet, Emmy Noether Grp, Weyertal 121,Room 111-10, D-50931 Cologne, Germany. OI Kuppers, Ralf/0000-0002-6691-7191 NR 70 TC 43 Z9 43 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 NOV 18 PY 2002 VL 196 IS 10 BP 1291 EP 1305 DI 10.1084/jem.20020881 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 618HL UT WOS:000179412600003 PM 12438421 ER PT J AU Prommer, EE AF Prommer, EE TI Hematologic aspects of Wilson's disease (hepatolenticular degeneration) SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 W Los Angeles VA, Div Hematol Oncol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3464 BP 4B EP 4B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800007 ER PT J AU Margossian, S de Oca, RM Andreassen, P Houghtaling, S Grompe, M D'Andrea, AD AF Margossian, S de Oca, RM Andreassen, P Houghtaling, S Grompe, M D'Andrea, AD TI Regulated interaction of the Fanconi anemia protein, FANCD2, with damaged chromatin. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Eugene, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 20 BP 9A EP 9A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700021 ER EF