FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Cooley, ME Short, TH Moriarty, HJ AF Cooley, ME Short, TH Moriarty, HJ TI Patterns of symptom distress in adults receiving treatment for lung cancer SO JOURNAL OF PALLIATIVE CARE LA English DT Article ID QUALITY-OF-LIFE; PALLIATIVE CARE; HEALTH; DISEASE; TRIAL; AGE; CHEMOTHERAPY; PREVALENCE; EXPERIENCE; DIAGNOSIS AB Knowledge of the patterns of symptom distress in adults receiving treatment for lung cancer is an important first step in developing interventions that can potentially lessen symptom distress. The purposes of this secondary analysis were to describe the changes in patterns of symptom distress over time in adults receiving treatment for lung cancer, and to examine the relationship of selected demographic and clinical characteristics to symptom distress. Complete data were available for 117 patients. The patterns of symptom distress in adults receiving treatment for lung cancer varied between treatment groups and over time. Symptom distress scores were moderate to high on entry into the study, indicating that symptom management in newly diagnosed lung cancer patients is essential and should begin early in the course of illness. Moreover, clinical interventions should be tailored to the type of treatment. Various demographic and clinical variables were weak and inconsistent predictors of symptom distress, underscoring the importance of examining the role of psychosocial factors in mediating symptom distress. C1 Harvard Univ, Sch Med, Sch Dent Med, Smoking Cessat Res Program, Boston, MA 02115 USA. Indiana Univ Penn, Dept Math, Indiana, PA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cooley, ME (reprint author), Harvard Univ, Sch Med, Sch Dent Med, Smoking Cessat Res Program, Boston, MA 02115 USA. FU NINR NIH HHS [T32 NR07035] NR 58 TC 30 Z9 30 U1 0 U2 2 PU CENTER BIOETHICS CLIN RES INST MONTREAL PI MONTREAL PA 110 PINE AVE W, MONTREAL, QUEBEC H2W 1R7, CANADA SN 0825-8597 J9 J PALLIATIVE CARE JI J. Palliative Care PD FAL PY 2002 VL 18 IS 3 BP 150 EP 159 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 612AD UT WOS:000179050100003 PM 12418365 ER PT J AU Grunfeld, E Whelan, T Reyno, L Earle, C Willan, AR Coyle, D Coristine, M Foster, G AF Grunfeld, E Whelan, T Reyno, L Earle, C Willan, AR Coyle, D Coristine, M Foster, G TI Use of health services and supportive care services by women with advanced breast cancer toward the end of life: Results of a longitudinal study SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 Univ Ottawa, Ottawa Reg Canc Ctr, Ottawa Hlth Res Inst, Support Canc Care Res Unit, Ottawa, ON, Canada. McMaster Univ, Hamilton Reg Canc Ctr, Support Canc Care Res Unit, Hamilton, ON, Canada. Hlth Sci Ctr, Halifax, NS, Canada. Dalhousie Univ, Halifax, NS, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Whelan, Timothy/D-3185-2017 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CENTER BIOETHICS CLIN RES INST MONTREAL PI MONTREAL PA 110 PINE AVE W, MONTREAL, QUEBEC H2W 1R7, CANADA SN 0825-8597 J9 J PALLIATIVE CARE JI J. Palliative Care PD FAL PY 2002 VL 18 IS 3 BP 209 EP 209 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 612AD UT WOS:000179050100023 ER PT J AU Suntsova, N Szymusiak, R Alam, MN Guzman-Marin, R McGinty, D AF Suntsova, N Szymusiak, R Alam, MN Guzman-Marin, R McGinty, D TI Sleep-waking discharge patterns of median preoptic nucleus neurons in rats SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SLOW-WAVE SLEEP; MONOAMINERGIC CELL GROUPS; LOCUS COERULEUS NEURONS; DORSAL RAPHE NEURONS; POSTERIOR HYPOTHALAMUS; POSSIBLE INVOLVEMENT; PROSTAGLANDIN D-2; PROMOTING ZONE; REM-SLEEP; IN-VITRO AB Several lines of evidence show that the preoptic area (POA) of the hypothalamus is critically implicated in the regulation of sleep. Functionally heterogeneous cell groups with sleep-related discharge patterns are located both in the medial and lateral POA. Recently a cluster of neurons showing sleep-related c-Fos immunoreactivity was found in the median preoptic nucleus (MnPN). To determine the specificity of the state-related behaviour of MnPN neurons we have undertaken the first study of their discharge patterns across the sleep-waking cycle. Nearly 76 % of recorded cells exhibited elevated discharge rates during sleep. Sleep-related units showed several distinct types of activity changes across sleep stages. Two populations included cells displaying selective activation during either non-rapid eye movement (NREM) sleep (10 %) or REM sleep (8 %). Neurons belonging to the predominant population (58 %) exhibited activation during both phases of sleep compared to wakefulness. Most of these cells showed a gradual increase in their firing rates prior to sleep onset, elevated discharge during NREM sleep and a further increase during REM sleep. This specific sleep-waking discharge profile is opposite to that demonstrated by wake-promoting monoaminergic cell groups and was previously found in cells localized in the ventrolateral preoptic area (vlPOA). We hypothesize that these vlPOA and MnPN neuronal populations act as parts of a GABAergic/galaninergic sleep-promoting ('anti-waking') network which exercises inhibitory control over waking-promoting systems. MnPN neurons that progressively increase activity during sustained waking and decrease activity during sustained sleep states may be involved in homeostatic regulation of sleep. C1 VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med & Neurobiol, Los Angeles, CA 90024 USA. Rostov State Univ, AB Kogan Res Inst Neurocybernet, Rostov Na Donu 344090, Russia. RP McGinty, D (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. FU NHLBI NIH HHS [HL 60296, P50 HL060296]; NIMH NIH HHS [MH 04708, MH 47480, R01 MH047480] NR 74 TC 95 Z9 98 U1 1 U2 3 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 SEP 1 PY 2002 VL 543 IS 2 BP 665 EP 677 DI 10.1113/jphsiol.2002.023085 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 596VB UT WOS:000178186200023 PM 12205198 ER PT J AU Sattar, SP Gastfriend, DR AF Sattar, SP Gastfriend, DR TI Olanzapine-induced hyperventilation: case report SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article DE antipsychotic agents; dyspnea; hyperventilation; methadone; schizophrenia ID VENTILATION; DYSKINESIA; QUETIAPINE; SEROTONIN; DOPAMINE AB Although olanzapine therapy has been associated with fewer extrapyramidal side effects than the traditional antipsychotic medications, reported side effects include dystonia, tardive dyskinesia, hypotension, diabetes mellitus, seizures and neuroleptic malignant syndrome. There are no previous published reports of hyperventilation associated with olanzapine therapy, but we present the case of a male patient who developed dyspnea and hyperventilation while taking olanzapine. C1 Creighton Univ, Sch Med, Dept Psychiat, Omaha, NE USA. Massachusetts Gen Hosp, Addict Res Program, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sattar, SP (reprint author), Creighton Univ, Sch Med, Dept Psychiat, 3528 Dodge St, Omaha, NE USA. FU NIDA NIH HHS [K24 DA000427, K24-DA00427] NR 18 TC 0 Z9 0 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD SEP PY 2002 VL 27 IS 5 BP 360 EP 363 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 593GV UT WOS:000177983400005 PM 12271791 ER PT J AU Thompson, RL Brossart, DF Carlozzi, AF Miville, ML AF Thompson, RL Brossart, DF Carlozzi, AF Miville, ML TI Five-factor model (Big Five) personality traits and universal-diverse orientation in counselor trainees SO JOURNAL OF PSYCHOLOGY LA English DT Article DE counselor training; diversity; five-factor model of personality; NEO-PI; universal-diverse orientation ID 5-FACTOR MODEL; PERCEPTIONS; OPENNESS AB In this study the authors explored the relationship between five-factor model (FFM: Big Five) personality traits (J. M. Digman, 1990; R. R. McCrae & O. P John, 1992; J. S, Wiggins & P. D. Trappnell, 1997) and universal-diverse orientation (UDO; M. L. Miville et al., 1999) in counselor trainees. FFM traits were measured using the NEO-Personality Inventory-Revised (P. T Costa & R. R. McCrae, 1992). Statistically significant relationships were found between UDO and one of the Big Five personality traits (Openness to Experience) in Counselor trainees. Further regression analysis suggested a relationship between UDO and a particular facet of Openness to Experience, Openness to Aesthetics. This finding suggests that counselor trainees who are open to the creative expressions of others may be comfortable working with a wide variety of clients. These results suggest that counselor training that encourages experiences of aesthetic diversity in addition to an exploration of values may promote trainees' ability to work with diverse clients. C1 Texas A&M Univ, S Texas Vet Hlth Care Syst, College Stn, TX 77843 USA. Texas A&M Univ, Dept Educ Psychol, College Stn, TX 77843 USA. Oklahoma State Univ, Sch Appl Hlth & Educ Psychol, Stillwater, OK 74078 USA. RP Thompson, RL (reprint author), Texas A&M Univ, S Texas Vet Hlth Care Syst, College Stn, TX 77843 USA. NR 42 TC 18 Z9 18 U1 1 U2 4 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0022-3980 J9 J PSYCHOL JI J. Psychol. PD SEP PY 2002 VL 136 IS 5 BP 561 EP 572 PG 12 WC Psychology, Multidisciplinary SC Psychology GA 613AR UT WOS:000179108600007 PM 12431039 ER PT J AU Sonawalla, SB Farabaugh, A Johnson, MW Morray, M Delgado, ML Pingol, MG Rosenbaum, JF Fava, M AF Sonawalla, SB Farabaugh, A Johnson, MW Morray, M Delgado, ML Pingol, MG Rosenbaum, JF Fava, M TI Fluoxetine treatment of depressed patients with comorbid anxiety disorders SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE anxiety; comorbid anxiety disorder; fluoxetine; major depression; open trial ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSION; SOCIAL PHOBIA; SYMPTOM QUESTIONNAIRE; ANXIOUS DEPRESSION; DOSE FLUOXETINE; PANIC DISORDER; PLACEBO; EFFICACY AB Major depression with comorbid anxiety disorder is associated with poor antidepressant outcome compared to major depression without comorbid anxiety disorder. The purpose of our study was to assess changes in severity of both depressive and anxiety symptoms in outpatients with major depression with comorbid anxiety disorder following fluoxetine treatment. We enrolled 123 outpatients (mean age 38.9 +/- 10.8 years; 49% women) with major depressive disorder accompanied by one or more current comorbid anxiety disorders in our study. Patients were treated openly with fluoxetine 20 mg/day for 8 weeks. Efficacy assessments included the 17-item Hamilton Rating Scale for Depression (HAM-D) and the patient-rated Symptom Questionnaire (SQ) Scales for Depression and Anxiety. The mood and anxiety disorder modules of the Structured Clinical Interview for DSM-III-R were administered at screen and endpoint. We used 'intent-to-treat' analysis in examining all patients assigned to treatment and completing the baseline visit. The mean number of comorbid anxiety disorders per patient was 1.5 +/- 0.68. The mean HAM-D-17 score and mean Clinical Global Impressions-Severity scores decreased significantly from baseline to endpoint (week 8) following fluoxetine treatment (p < 0.0001). There were significant decreases in all four SQ scale scores, from baseline to endpoint: depression, anxiety, somatic symptoms and anger-hostility (p < 0.0001). Fifty-three percent of patients (n = 65) were depression responders (i.e. greater than or equal to 50% decrease in HAM-D-17 score at endpoint) and 46% (n = 57) were remitters (HAM-D-17 :5 7 at endpoint). Patients with panic disorder had significantly higher baseline HAM-D-17 scores compared to those without panic disorder (p < 0.01). Patients with comorbid obsessive-compulsive disorder (OCD) were significantly less likely to be responders to fluoxetine at endpoint (greater than or equal to 50% decrease in HAM-D-17) and to be remitters (HAM-D-17 score of less than or equal to 7 at endpoint) compared to patients without comorbid OCD (p < 0.01). Of the 41 patients on whom endpoint Structured Clinical Interview for DSM-III-R modules for anxiety disorders were available, 49% (n = 20) no longer met criteria for one or more of their anxiety disorder diagnoses at endpoint. Our preliminary findings suggest that fluoxetine is effective in treating outpatients with major depression with comorbid anxiety disorders, with a significant effect on both depression and anxiety symptoms. Further double-blind, placebo-controlled trials are required in larger samples to confirm our findings. C1 Harvard Univ, Sch Med, Depress Clin & Res Program, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sonawalla, SB (reprint author), Harvard Univ, Sch Med, Depress Clin & Res Program, Massachusetts Gen Hosp, WACC 812,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [R01-MH-48-483-05] NR 44 TC 12 Z9 14 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2002 VL 16 IS 3 BP 215 EP 219 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 594FU UT WOS:000178039200004 PM 12236627 ER PT J AU Marder, SR Saba, AR Kaplita, SB Archibald, DG McQuade, RD AF Marder, SR Saba, AR Kaplita, SB Archibald, DG McQuade, RD TI Safety and tolerability meta-analysis of aripiprazole in schizophrenia SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychopharmacology CY JUL 21-24, 2002 CL HARROGATE, ENGLAND C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Otsuka Maryland Res Inst LLC, Rockville, MD USA. Bristol Myers Squibb Co, Lawrenceville, NJ USA. Bristol Myers Squibb Co, Plainsboro, NJ USA. Otsuka Pharmaceut Co Ltd, Tokyo, Japan. Univ Calif Los Angeles, Sch Med, W LA VA Med Ctr, VA Greater LA Healthcare Syst,Psychiat Serv 116A, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2002 VL 16 IS 3 SU S MA A31 BP A17 EP A17 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 595EN UT WOS:000178094000067 ER PT J AU Vaughan, NE Fausti, SA Chelius, S Phillips, D Helt, W Henry, JA AF Vaughan, NE Fausti, SA Chelius, S Phillips, D Helt, W Henry, JA TI An efficient test protocol for identification of a limited, sensitive frequency test range for early detection of ototoxicity SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE ototoxicity; rapid identification protocol; sensitive range of ototoxicity (SRO); uppermost target frequency ID OTOACOUSTIC EMISSIONS; CISPLATIN OTOTOXICITY AB A primary focus of research at the National Center for Rehabilitative Auditory Research (NCRAR) has been to develop methodology for rapid and efficient early detection of ototoxicity. It has been shown that an individualized, limited frequency range can be identified, which is sensitive to early ototoxic changes in the auditory system. In this study, a rapid identification protocol for identifying the uppermost target frequency within this sensitive range of ototoxicity (SRO) was investigated. In 36 of 42 ears, the target frequency found with the rapid identification protocol was the same as that found with the full-frequency baseline testing. Where differences occurred, target frequencies obtained by the two methods did not differ by more than one-half octave. This rapid identification protocol results in considerable time savings in ototoxicity monitoring, which will result in the capability to include more patients in a monitoring program. C1 Portland VA Med Ctr, RR&D Natl Ctr Rehab Auditory Res, Dept Vet Affairs, Portland, OR 97207 USA. RP Vaughan, NE (reprint author), Portland VA Med Ctr, RR&D Natl Ctr Rehab Auditory Res, Dept Vet Affairs, POB 1034, Portland, OR 97207 USA. NR 14 TC 10 Z9 10 U1 1 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2002 VL 39 IS 5 BP 567 EP 573 PG 7 WC Rehabilitation SC Rehabilitation GA 667UY UT WOS:000182253500005 PM 17642021 ER PT J AU Reiber, GE Smith, DG Wallace, CM Vath, CA Sullivan, K Hayes, S Yu, O Martin, D Maciejewski, M AF Reiber, GE Smith, DG Wallace, CM Vath, CA Sullivan, K Hayes, S Yu, O Martin, D Maciejewski, M TI Footwear used by individuals with diabetes and a history of foot ulcer SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE diabetes mellitus; foot ulcer; footwear costs; shoes ID THERAPEUTIC FOOTWEAR; NEUROPATHIC FOOT; PREVENTION; AMPUTATION; PATHWAYS AB Objective. To describe footwear preferences of people with diabetes and a history of foot ulcer from two large western Washington State healthcare organizations. Methods. As part of a clinical trial of footwear, self-reported information on footwear preferences, use, and cost were obtained from persons with diabetes and a prior healed foot ulcer for the year before their study enrollment. All participants' shoes were allocated into optimal, adequate, and dangerous categories based on design, structural and safety features, and materials. Results. The 309 males and 91 females in this study averaged 62 years of age. At baseline, men owned an average of 6 (+3) pairs of shoes, with an average purchase price of $56, while women owned an average of 8 (+5) pairs, with an average purrchase price of $42. Women spent an average of 51% of their time in shoes in dangerous shoes compared to men who spent 27% of their time. Men and women spent nearly 30% of their time while out of bed in slippers, stockings, and barefoot. Conclusions. People with a history of diabetes and foot ulcers needed several styles of safe and attractive shoes for regular activities. Healthcare professionals can provide patients with information on good footwear choices to help them select adequate shoes while avoiding dangerous shoes. This approach is more realistic than trying to move all people with prior foot risk factors or ulcers into uniformly optimal footwear, since recent evidence does not support this practice. C1 VA Puget Sound Hlth Care Syst 152, Dept Vet Affairs, Hlth Serv & Rehab Res & Dev, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA USA. Univ Washington, Dept Orthopaed Surg, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Joslin Diabet Ctr, Swedish Med Ctr, Seattle, WA USA. RP Reiber, GE (reprint author), VA Puget Sound Hlth Care Syst 152, Dept Vet Affairs, Hlth Serv & Rehab Res & Dev, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 18 TC 11 Z9 11 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2002 VL 39 IS 5 BP 615 EP 621 PG 7 WC Rehabilitation SC Rehabilitation GA 667UY UT WOS:000182253500010 PM 17642026 ER PT J AU Friedlander, AH Friedlander, IK Marder, SR AF Friedlander, AH Friedlander, IK Marder, SR TI Bipolar I disorder - Psychopathology, medical management and dental implications SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; ADVERSE DRUG-INTERACTIONS; PSYCHOSOCIAL FACTORS; MAINTENANCE TREATMENT; DEPRESSIVE SYMPTOMS; CIGARETTE-SMOKING; INDUCED BRUXISM; VALPROATE; LITHIUM; SERIES AB Background. The authors review the clinical features, epidemiology, pathophysiology, medical management, dental findings and dental management of patients who have bipolar I disorder, or BD, previously known as manic-depressive disorder. Types of Studies Reviewed. The authors conducted a MEDLINE search for the period 1995 through 2001 using the key terms "bipolar disorder," "epidemiology," " pathophysiology," "treatment" and "dentistry." The articles they selected for further review included those published in English in peer-reviewed journals; they gave preference to articles reporting randomized, controlled trials. Results. BD is a psychiatric illness characterized by extreme mood swings. Mania is accompanied by euphoria, grandiosity, racing thoughts and lack of insight. Depression is characterized by marked sadness or loss of interest or pleasure in daily activities. The unpredictable mood swings can distress the person, can impair social function and quality of life and are associated with a significant increase in the risk for substance abuse and suicide. BD is common in the United States, with a lifetime prevalence rate of 1.6 percent and recurrence rate of more than 50 percent. Clinical Implications. The prevalence of dental disease usually is extensive because of poor oral hygiene and medication-induced xerostomia. Preventive dental education, saliva substitutes and anticaries agents are indicated. To avoid adverse drug interactions with the usually prescribed psychiatric medications, special precautions should be taken when administering certain antibiotics, analgesics and sedatives. C1 W Valley Los Angeles Cty Dept Hlth, Van Nuys, CA USA. Dept Vet Affairs, Mental Illness Res Educ & Clin Ctr VISN22, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 84 TC 23 Z9 23 U1 3 U2 6 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2002 VL 133 IS 9 BP 1209 EP 1217 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 595KK UT WOS:000178107900017 PM 12356252 ER PT J AU Schnelle, JF Alessi, CA Simmons, SF Al-Samarrai, NR Beck, JC Ouslander, JG AF Schnelle, JF Alessi, CA Simmons, SF Al-Samarrai, NR Beck, JC Ouslander, JG TI Translating clinical research into practice: A randomized controlled trial of exercise and incontinence care with nursing home residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE practice guidelines; dissemination barriers; labor requirements ID ILLNESS RATING-SCALE; INTERVENTION; TECHNOLOGY; RISK AB OBJECTIVES: To examine clinical outcomes and describe the staffing requirements of an incontinence and exercise intervention. DESIGN: Randomized controlled trial with blinded assessments of outcomes at three points over 8 months. SETTING: Four nursing homes. PARTICIPANTS: Two hundred fifty-six incontinent residents. INTERVENTION: Research staff provided the intervention, which integrated incontinence care and exercise every 2 hours from 8:00 a.m. to 4:00 p.m. 5 days a week. MEASUREMENTS: Average and maximum distance walked or wheeled, level of assistance required to stand, maximum pounds lifted by arms, fecal and urinary incontinence frequency, and time required to implement intervention. RESULTS: Intervention residents maintained or improved performance whereas the control group's performance declined on 14 of 15 outcome measures. Repeated measures analysis of variance group-by-time significance levels ranged from P <.0001 to.05. The mean time required to implement the intervention each time care was provided was 20.7 +/- 7.2 minutes. We estimate that a work assignment of approximately five residents to one aide would be necessary to provide this intervention. CONCLUSIONS: The incontinence care and exercise intervention resulted in significant improvement for most residents, and most who could be reliably interviewed expressed a preference for such care. Fundamental changes in the staffing of most nursing homes will be necessary to translate efficacious clinical interventions into everyday practice. C1 Borun Ctr, UCLA Los Angeles Jewish Home Aging, Reseda, CA 91335 USA. Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. Emory Univ, Div Geriatr Med & Gerontol, Wesley Woods Ctr, Atlanta, GA 30322 USA. Atlanta VA Rehabil Res & Dev Ctr, Atlanta, GA USA. RP Schnelle, JF (reprint author), Borun Ctr, UCLA Los Angeles Jewish Home Aging, 7150 Tampa Ave, Reseda, CA 91335 USA. FU NIA NIH HHS [AG10415, AG13013] NR 30 TC 144 Z9 144 U1 2 U2 4 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 SEP PY 2002 VL 50 IS 9 BP 1476 EP 1483 DI 10.1046/j.1532-5415.2002.50401.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 593AE UT WOS:000177968400001 PM 12383143 ER PT J AU Vig, EK Davenport, NA Pearlman, RA AF Vig, EK Davenport, NA Pearlman, RA TI Good deaths, bad deaths, and preferences for the end of life: A qualitative study of geriatric outpatients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 1st International Geriatric Palliative Care Congress CY OCT, 2000 CL NEW YORK, NEW YORK DE older; end of life; attitude to death; terminal care; patient-centered care ID MENTAL STATUS QUESTIONNAIRE; OF-LIFE; ELDERLY PATIENTS; SUSTAINING TREATMENTS; TERMINAL ILLNESS; FAMILY MEMBERS; OLDER ADULTS; CARE; STABILITY; VIEWS AB OBJECTIVES: Patient involvement in decision-making has been advocated to improve the quality of life at the end of life. Although the size of the oldest segment of the population is growing, with greater numbers of older adults facing the end of life, little is known about their preferences for the end of life. This study aimed to explore the attitudes of older adults with medical illness about the end of life, and to investigate whether current values could be extended to end-of-life preferences. DESIGN: Descriptive study with interviews using open- and closed-ended questions. SETTING: Patients attending two university-affiliated geriatric clinics were interviewed in a private conference room near the clinic they attended or in their homes. PARTICIPANTS: Sixteen older men and women identified by their physicians as having nonterminal heart disease or cancer. MEASUREMENTS: The interview contained open-ended questions such as: "What are the most important things in your life right now?" and "What would you consider a good/bad death?" The interview also contained closed-ended questions about symptoms, quality of life, and health status. Additional questions elicited preferences for the end of life, such as location of death and the presence of others. The open-ended questions were tape-recorded, transcribed, and analyzed using qualitative methods. The closed-ended questions were analyzed using descriptive statistics. RESULTS: Patients with heart disease and cancer provided similar responses. Participants' views about good deaths, bad deaths, and end-of-life scenarios were heterogeneous. Each participant voiced a unique combination of themes in describing good and bad deaths. Because each participant described a multifaceted view of a good death, for instance, no theme was mentioned by even half of the participants. Participants provided differing explanations for why given themes contributed to good deaths. Currently valued aspects of life were not easily translated into end-of-life preferences. For example, although the majority of participants identified their family as being important, many gave reasons why they did not want their family members present when they died. CONCLUSIONS: Because of the heterogeneity of views and the difficulty in inferring end-of-life preferences from current values, older adults should be asked not only questions about general values, but also specific questions about their end-of-life choices and the reasons for these choices. A thorough understanding of an individual's end-of-life preferences may help health professionals working with older adults develop patient-centered care plans for the end of life. C1 Univ Washington, Harborview Med Ctr, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Vig, EK (reprint author), Univ Washington, Harborview Med Ctr, Div Gerontol & Geriatr Med, 325 9th Ave,Box 359755, Seattle, WA 98104 USA. NR 38 TC 52 Z9 53 U1 3 U2 8 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 SEP PY 2002 VL 50 IS 9 BP 1541 EP 1548 DI 10.1046/j.1532-5415.2002.50410.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 593AE UT WOS:000177968400010 PM 12383152 ER PT J AU Yukawa, M McCormick, WC Rajan, S Matsumoto, AM Wallace, JI Pearlman, RA Weigle, DS AF Yukawa, M McCormick, WC Rajan, S Matsumoto, AM Wallace, JI Pearlman, RA Weigle, DS TI Leptin levels are appropriate for body mass index in older men who experience involuntary weight SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE serum leptin levels; involuntary weight loss; body mass index ID STAGE RENAL-DISEASE; SERUM LEPTIN; CIRCULATING LEPTIN; NUTRITIONAL-STATUS; ANOREXIA-NERVOSA; FAT-CONTENT; WOMEN; TESTOSTERONE; HYPERINSULINEMIA; ASSOCIATION AB OBJECTIVES: To determine the relationship between leptin and unintentional weight loss In older adults. DESIGN: Prospective cohort study over 2 years. SETTING: University-affiliated Veterans Affairs Medical Center. PARTICIPANTS: The subjects were 105 community-dwelling male veterans aged 65 and older who had participated in a prospective cohort study on nutrition and health conducted at the Veterans Affairs Puget Sound Health Care System from 1986 to 1989. MEASUREMENTS: Anthropometric data and fasting blood specimens were collected at baseline and annually for the subsequent 2 years. Stored blood specimens were analyzed for leptin, insulin, glucose, C-reactive protein, sex hormone binding globulin, and testosterone levels. RESULTS: Over 2 years, 75 men were weight stable (weight loss <4% of baseline) and 30 men had unintentional weight loss (weight loss >4% of baseline). The baseline body mass index (BMI) and leptin levels for the two groups were not statistically different. Positive correlations existed between leptin level and BMI at each time point for weight-stable and weight-loss subjects. Furthermore, a significant relationship existed between changes ill leptin and changes in BMI over 1 year in multiple regression analysis (r =.436, P <.001 after the first year; and r =.630, P =.027 after the second year). CONCLUSIONS: Like in younger adults, plasma leptin levels remained proportional to BMI, and changes in BMI were accurately reflected by changes in leptin levels in older individuals. Fasting leptin levels did not predict involuntary weight loss over 2 years of follow-up. C1 Univ Washington, Harborview Med Ctr, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. Univ Washington, Div Endocrinol, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Colorado, Hlth Sci Ctr, Div Geriatr, Denver, CO USA. RP Yukawa, M (reprint author), Univ Washington, Harborview Med Ctr, Div Gerontol & Geriatr Med, 325 9th Ave,Box 359755, Seattle, WA 98104 USA. FU NIDDK NIH HHS [DK02860] NR 46 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2002 VL 50 IS 9 BP 1566 EP 1571 DI 10.1046/j.1532-5415.2002.50414.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 593AE UT WOS:000177968400014 PM 12383156 ER PT J AU Friedlander, AH Jones, LJ AF Friedlander, AH Jones, LJ TI The biology, medical management, and podiatric implications of menopause SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID HORMONE REPLACEMENT THERAPY; ESTROGEN-RECEPTOR MODULATORS; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; OSTEOPOROTIC FRACTURES; RISK-FACTORS; ELDERLY WOMEN; HIP FRACTURE; POPULATION; PREVENTION AB Approximately 36 million women in the United States are in the postmenopausal phase of life, creating unique challenges for the provision of compassionate, comprehensive podiatric medical treatment. Longterm estrogen deprivation arising from menopause in association with age-related factors disproportionately increases the risk of ischemic heart disease, osteoporosis, and concomitant podiatric complications. This article discusses the physiologic basis of menopause, hormone replacement therapy and its effects on osteoporosis, and other podiatric implications of menopause. Podiatric physicians caring for larger numbers of peri- and postmenopausal women must formulate a comprehensive management plan for treating fractures that arise from a combination of estrogen-deprivation osteoporosis and abnormal foot biomechanics. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA USA. NR 67 TC 1 Z9 1 U1 0 U2 2 PU AMER PODIATRIC MED ASSN PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD SEP PY 2002 VL 92 IS 8 BP 437 EP 443 PG 7 WC Orthopedics SC Orthopedics GA 595KM UT WOS:000178108200003 PM 12237264 ER PT J AU Senthil, D Choudhury, GG Bhandari, BK Kasinath, BS AF Senthil, D Choudhury, GG Bhandari, BK Kasinath, BS TI Requirement of IRS-I for regulation of protein synthesis by VEGF in proximal tubular epithelial (PTE) cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 16A EP 16A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500076 ER PT J AU Thio, SSC Bonventre, JV Hsu, SI AF Thio, SSC Bonventre, JV Hsu, SI TI TIF1 alpha and CtBP-2 form a novel co-repressor complex. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Natl Univ Singapore, Dept Med, Singapore, Singapore. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 23A EP 23A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500110 ER PT J AU Sim, KG Yang, CM Bonventre, JV Hsu, SI AF Sim, KG Yang, CM Bonventre, JV Hsu, SI TI The integrator function of TRIP-Br transcription factors is required for proper execution of mammalian cell cycle progression. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Natl Univ Singapore, Fac Med, Dept Med, Singapore 117548, Singapore. Natl Univ Singapore, Fac Med, Inst Mol & Cell Biol, Singapore 117548, Singapore. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 33A EP 33A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500162 ER PT J AU O'Hare, AM Navarro, D Hynes, D Colin, P Dudley, A Stroupe, K McCulloch, C Rapp, J Johansen, KL AF O'Hare, AM Navarro, D Hynes, D Colin, P Dudley, A Stroupe, K McCulloch, C Rapp, J Johansen, KL TI High percentage of autogenous AV-fistula placement in the VA Healthcare System nationally. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 San Francisco VAMC, San Francisco, CA USA. UCSF, San Francisco, CA USA. Hines VAMC, VIREC, Chicago, IL 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 37A EP 37A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500183 ER PT J AU Muckova, K Bonventre, JV Alessandrini, A Sheridan, AM AF Muckova, K Bonventre, JV Alessandrini, A Sheridan, AM TI The role of a putative calcium/calmodulin kinase (CamK) II site in the regulation of cytosolic phospholipase A(2) (cPLA(2)) activity. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Dept, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 83A EP 84A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500408 ER PT J AU Gooch, JL Gorin, Y Zhang, B Abboud, HE AF Gooch, JL Gorin, Y Zhang, B Abboud, HE TI Calcineurin is activated by mobilization of extracellular calcium in mesangial cells and is required for accumulation of matrix proteins by TGFb beta. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 86A EP 86A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500422 ER PT J AU Riley, DJ Feliers, D AF Riley, DJ Feliers, D TI Rb and AP-1 positively regulate transcription of the cyclin D1 gene during renal and mesangial hypertrophy. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, Div Res, 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 91A EP 91A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500446 ER PT J AU Li, SX Daniel, CD Balkovetz, DF AF Li, SX Daniel, CD Balkovetz, DF TI Hepatocyte growth factor increases cyclin D1 in contact inhibited renal epithelial cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 92A EP 92A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500449 ER PT J AU Lu, WN Herron, BJ Arnaout, MA Beier, DR AF Lu, WN Herron, BJ Arnaout, MA Beier, DR TI Characterization of an ENU-induced mutation of the Pkd1 gene in the mouse. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Renal, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 112A EP 113A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500557 ER PT J AU Liu, SM Obara-Ishihara, T Drummond, IA Beier, DR AF Liu, SM Obara-Ishihara, T Drummond, IA Beier, DR TI Characterization of Nek8, the gene mutated in the jck mouse model of polycystic kidney disease. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Renal, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 116A EP 116A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500577 ER PT J AU Canani, LH Bochenski, J Hanna, LS Ng, DPK Warram, JH Krolewski, AS AF Canani, LH Bochenski, J Hanna, LS Ng, DPK Warram, JH Krolewski, AS TI Ecto-nucleotide pyrophosphatase/phosphodiesterase 1(ENNP1) polymorphism. (K121Q) and the development of microalbuminuria (MA) in type 1 diabetes (DM1). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 247A EP 247A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501210 ER PT J AU Ng, DPK Warram, JH Krolewski, AS AF Ng, DPK Warram, JH Krolewski, AS TI Exclusion of transforming growth factor-beta 1 (TGF-beta 1) as a susceptibility gene for advanced diabetic nephropathy in type 1 diabetes mellitus. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 247A EP 247A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501208 ER PT J AU Beaulieu, V Pastor-Soler, N Da Silva, N McKee, M Smith, P Brown, D Breton, S AF Beaulieu, V Pastor-Soler, N Da Silva, N McKee, M Smith, P Brown, D Breton, S TI Role of the actin cytoskeleton and luminal pH in the regulation of H(+)ATPasc recycling in the epididymis and vas deferens. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Program Membrane Biol, Charlestown, MA USA. Biol Marine Lab, BioCurrents Res Ctr, Woods Hole, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 268A EP 268A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501312 ER PT J AU Miller, RL Smith, MJ Brown, D Breton, S Nelson, RD AF Miller, RL Smith, MJ Brown, D Breton, S Nelson, RD TI Specific expression of green fluorescent protein in kidney intercalated cells and epididymal narrow/clear cells of transgenic mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Utah, Sch Med, Salt Lake City, UT USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 269A EP 269A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501318 ER PT J AU Tian, W Cohen, DM AF Tian, W Cohen, DM TI Urea stress resembles EGF treatment more than it resembles hypertonic stress. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Div Nephrol & Hypertens, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 275A EP 276A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501352 ER PT J AU Raychowdhury, MK Primo, VC Burns, N Cantiello, HF AF Raychowdhury, MK Primo, VC Burns, N Cantiello, HF TI Molecular characterization of sodium channel proteins in the porcine renal epithelial cell line, LLC-PK1. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp East, Renal Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Dept 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 279A EP 279A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501369 ER PT J AU Jara, A Chacon, C Valdivieso, A Ibaceta, M Felsenfeld, A AF Jara, A Chacon, C Valdivieso, A Ibaceta, M Felsenfeld, A TI Effect of chronic metabolic acidosis on renal function and mineral metabolism in 5/6 nephrectomized rats on low and high phosphate diets. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Pontificia Univ, Nephrol Dept, Rio De Janeiro, Brazil. Santiago Chile & Dept Med, W Los Angeles VA, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 281A EP 281A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501379 ER PT J AU Pastor-Soler, NM Da Silva, N Zhou, WL Chen, YQ Levin, LR Buck, J Breton, S AF Pastor-Soler, NM Da Silva, N Zhou, WL Chen, YQ Levin, LR Buck, J Breton, S TI Expression of soluble adenylyl cyclase (sAQ in epithelial cells of the epididymis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 285A EP 285A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501402 ER PT J AU Hung, CC Takaharu, I Stevens, JL Bonventre, JV AF Hung, CC Takaharu, I Stevens, JL Bonventre, JV TI Endoplasmic reticulum stress proteins block H2O2-induced cell death in LLC-PK1 cells by preventing cytoplasmic Ca2+ perturbation and modulating ERK1/2 and JNK signaling pathways. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Lilly Res Labs, Greenfield, IN 46140 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 286A EP 286A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501408 ER PT J AU Hsieh, TJ Zhang, SL Filep, JG Fantus, IG Tang, SS Ingelfinger, JR Chan, JSD AF Hsieh, TJ Zhang, SL Filep, JG Fantus, IG Tang, SS Ingelfinger, JR Chan, JSD TI High glucose stimulates angiotensinogen (ANG) gene expression via reactive oxygen species (ROS) generation, activation of hexosamine biosynthetic pathway (HBP) and p38 mitogen-activated protein kinase (p38 MAPK) in rat immortalized renal proximal tubular cells (IRPTCs). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 CHUM Hotel Dieu, Montreal, PQ, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Massachusetts Gen Hosp, Pediat Nephrol Unit, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 288A EP 288A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501419 ER PT J AU Calve, A Chen, X Zhang, SL Hebert, MJ Filep, JG Whiteside, CI Tang, SS Ingelfinger, JR Chan, JSD AF Calve, A Chen, X Zhang, SL Hebert, MJ Filep, JG Whiteside, CI Tang, SS Ingelfinger, JR Chan, JSD TI Stimulatory effect of high glucose on angiotensinogen (ANG) gene and a 70 kiloDalton (kDa) insulin responsive element-binding protein (IRE-BP) expression is mediated via protein kinase C (PKC)-alpha in rat immortalized renal proximal tubular cells (IRPTCs). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 CHUM Hotel Dieu, Res Ctr, Montreal, PQ, Canada. Univ Toronto, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 290A EP 290A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501428 ER PT J AU Kuehn, EW Park, KM Somlo, S Bonventre, JV AF Kuehn, EW Park, KM Somlo, S Bonventre, JV TI Expression of kidney injury molecule-1 (KIM-1) is associated with the development of interstitial fibrosis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA USA. Yale Univ, Sch Med, Nephrol Sect, New Haven, CT USA. Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 314A EP 314A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501551 ER PT J AU Zhang, ZW Wu, W Bonventre, JV AF Zhang, ZW Wu, W Bonventre, JV TI Kidney injury molecule-1 (KIM-1) modulates cell adhesion to matrix by metalloproteinase-regulated ectodomain shedding. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Med Serv, Charlestown, MA USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. MIT, Harvard Mit Div Hlth Sci & Technol, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 322A EP 322A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501592 ER PT J AU Bae, J Tolkoff-Rubin, NE Baid, S Ovuworie, CA Williams, WW Shih, VE Cosimi, AB Pascual, MA AF Bae, J Tolkoff-Rubin, NE Baid, S Ovuworie, CA Williams, WW Shih, VE Cosimi, AB Pascual, MA TI No differences in plasma homocysteine (Hcy) levels between cyclosporine (CsA)- or tacrolimus (TAC)- treated renal transplant recipients (RTR) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 372A EP 372A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501835 ER PT J AU O'Hare, AM Navarro, D McCulloch, C Hynes, D Colin, P Stroupe, K Dudley, A Rapp, J Johansen, KL AF O'Hare, AM Navarro, D McCulloch, C Hynes, D Colin, P Stroupe, K Dudley, A Rapp, J Johansen, KL TI Surgeon practice pattern and center procedure volume are associated with choice of initial permanent hemodialysis access in the VA Healthcare System. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 San Francisco VAMC, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VIREC, Hines VAMC, Chicago, IL 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 402A EP 403A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501982 ER PT J AU Kleinman, JG Kaufman, JS Reda, DJ Williams, DW Anderson, RJ AF Kleinman, JG Kaufman, JS Reda, DJ Williams, DW Anderson, RJ TI A model predicting the dose of epoetin in hemodialysis patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Dept Med, Milwaukee, WI USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. VA Boston Healthcare Syst, Dept Med, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. VA Med Ctr, VA Cooperat Studies Program Coordinating Ctr, Hines, IL USA. Univ Illinois, Sch Publ Hlth, Chicago, IL 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 422A EP 422A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502075 ER PT J AU Kestenbaum, B Seliger, S Wasse, H Ball, A Gillen, D Sherrard, D Stehman-Breen, C AF Kestenbaum, B Seliger, S Wasse, H Ball, A Gillen, D Sherrard, D Stehman-Breen, C TI Parathyroid hormone levels and the risk of left ventricular hypertrophy at the onset of dialysis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Washington, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA USA. RI Wasse, Haimanot/A-5726-2013 OI Wasse, Haimanot/0000-0001-5756-0242 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 434A EP 434A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502127 ER PT J AU Hung, AM Qureishy, O Wetmore, JB Lovett, DH Johansen, KL AF Hung, AM Qureishy, O Wetmore, JB Lovett, DH Johansen, KL TI Role of IL 1RA gene polymorphism in ESRD and cardiovascular disease. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 435A EP 436A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502135 ER PT J AU Knight, EL Mattix, HJ Curhan, GC AF Knight, EL Mattix, HJ Curhan, GC TI High-normal blood pressure and microalbumiuria. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 437A EP 437A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502141 ER PT J AU Weisbord, SD Bruns, FJ Saul, MI Chang, CH Palevsky, PM AF Weisbord, SD Bruns, FJ Saul, MI Chang, CH Palevsky, PM TI The high costs of acute renal failure following the administration of intravenous contrast media in hospitalized patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 447A EP 447A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502188 ER PT J AU Weisbord, SD Bruns, FJ Saul, MI Palevsky, PM AF Weisbord, SD Bruns, FJ Saul, MI Palevsky, PM TI Are intravenous fluids used to limit the risk of contrast nephropathy? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 447A EP 447A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502187 ER PT J AU Teng, M Wolf, M Ofsthun, N Lazarus, M Lowrie, E Thadhani, R AF Teng, M Wolf, M Ofsthun, N Lazarus, M Lowrie, E Thadhani, R TI Survival benefit of Zemplar compared with Calcijex among dialysis patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 461A EP 461A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502258 ER PT J AU Fried, L Naydeck, B Edmundowicz, D Sutton-Tyrrell, K Kuller, L Newman, A AF Fried, L Naydeck, B Edmundowicz, D Sutton-Tyrrell, K Kuller, L Newman, A TI Coronary calcification and mild-moderate renal insufficiency in elderly individuals SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Geriatr, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Cardiol, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 465A EP 466A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502279 ER PT J AU Han, WK Keating, J Alinani, A Loda, MF Bonventre, JV AF Han, WK Keating, J Alinani, A Loda, MF Bonventre, JV TI Kidney injury molecule-1 (KIM-1): Expression in human renal cell carcinoma SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp East, Charlestown, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 472A EP 473A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502313 ER PT J AU Nagami, GT Warech, EM AF Nagami, GT Warech, EM TI AT1 receptor blockade prevents the enhancement of AT1 receptor cell surface expression by low pH in cultured proximal tubule cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VA Greater LA Healthcare Syst, Nephrol Sect, Los Angeles, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 474A EP 475A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502323 ER PT J AU Nagami, GT Warech, EM AF Nagami, GT Warech, EM TI Low pH increases AT1a receptor promoter-driven reporter gene expression in cultured proximal tubule cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VA Greater LA Healthcare Syst, Nephrol Sect, Los Angeles, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 475A EP 475A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502324 ER PT J AU Sun, TX Blackburn, K Bouley, R McLaughlin, M Brown, D AF Sun, TX Blackburn, K Bouley, R McLaughlin, M Brown, D TI Inhibition of endocytosis results in rapid accumulation of cell surface AQP2 via a constitutive, S256 phosphorylation-independent pathway. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA USA. Massachusetts Gen Hosp, Renal Unit, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 480A EP 480A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502348 ER PT J AU Da Silva, N Beaulieu, V Knepper, M Breton, S AF Da Silva, N Beaulieu, V Knepper, M Breton, S TI The SNARE proteins SNAP-23 and syntaxin 3 are expressed in epithelial cells of the epididymis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Program Membrane Biol, Charlestown, MA USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 486A EP 486A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502380 ER PT J AU Hsieh, TJ Fustier, P Zhang, SL Hamet, P Filep, JG Carriere, S Tang, SS Ingelfinger, JR Chan, JSD AF Hsieh, TJ Fustier, P Zhang, SL Hamet, P Filep, JG Carriere, S Tang, SS Ingelfinger, JR Chan, JSD TI Blockade of renin-angiotensin system (RAS) activation restores insulin sensitivity on angiotensinogen (ANG) gene expression in rat immortalized renal proximal tubular cells (IRPTCs) in high glucose SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 CHUM, Hotel Dieu, Res Ctr, Montreal, PQ, Canada. Servier Canada, R&D, Laval, PQ, Canada. Massachusetts Gen Hosp, Pediat Nephrol Unit, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 494A EP 494A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502422 ER PT J AU Yamamoto, K Eslami, P Nyby, MD Tuck, ML Corry, DB AF Yamamoto, K Eslami, P Nyby, MD Tuck, ML Corry, DB TI Uric acid stimulate's vascular smooth muscle cell proliferation by increasing angiotensin II production. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Olive View Med Ctr, Sylmar, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 495A EP 495A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502425 ER PT J AU Senthil, D Choudhury, GG Bhandari, BK Kasinath, BS AF Senthil, D Choudhury, GG Bhandari, BK Kasinath, BS TI Angiotensin II (Ang II) regulates expression of vascular endothelial growth factor (VEGF) and type 2 VEGF receptor (VEGFR2) in proximal tubular epithelial (PTE) cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 496A EP 496A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502433 ER PT J AU Chen, T Wang, JF Ercolani, L AF Chen, T Wang, JF Ercolani, L TI G alpha i-2 dependent renal mitogenesis: RACK1 is a scaffold protein for the STAT-3 transcription factor. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Harvard Univ, Sch Med, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 501A EP 501A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502456 ER PT J AU Gorin, YC Simon, M Bhandari, B Choudhury, GG Abboud, HE AF Gorin, YC Simon, M Bhandari, B Choudhury, GG Abboud, HE TI Tumor necrosis factor-alpha modulates the apoptotic effect of Thy 1.1 antibody. Role of PI3-K/Akt/PKB-dependent NF-kB activation. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Hosp Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 502A EP 502A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502462 ER PT J AU Said, SM Hentschel, DM Bonventre, JV Hsu, SI AF Said, SM Hentschel, DM Bonventre, JV Hsu, SI TI C/EBP alpha and C/EBP beta repress the prostate specific antigen (PSA) promoter by competing with the androgen receptor for binding to androgen response elements. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Natl Univ Singapore, Dept Med, Singapore 117548, Singapore. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 505A EP 505A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502477 ER PT J AU Komers, R John, RF Jessie, LN Terry, OT Scott, MM Anderson, S AF Komers, R John, RF Jessie, LN Terry, OT Scott, MM Anderson, S TI Functional expression of endothelial nitric oxide (NO) synthase (eNOS, NOS3) and caveolin-1 (CAV-1) in diabetic kidney cortex. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Div Nephrol & Hypertens, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Res Serv, Portland, OR 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 532A EP 532A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502610 ER PT J AU Bhandari, BK Senthil, D Choudhury, GG Kasinath, BS AF Bhandari, BK Senthil, D Choudhury, GG Kasinath, BS TI Regulation or renal cortical protein tyrosine phosphatases (PTP) in mice with type 2 diabetes. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78285 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 535A EP 535A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502626 ER PT J AU Alkassab, F Muckova, K Bonventre, JV Sheridan, AM AF Alkassab, F Muckova, K Bonventre, JV Sheridan, AM TI Tip60 and PLIP localize to different compartments of renal proximal tubule cells derived from cPLA(2)(+/+) and cPLA(2)(-/-) mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Dept, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 544A EP 544A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502670 ER PT J AU Park, KM Byun, JY Huang, PL Bonventre, JV AF Park, KM Byun, JY Huang, PL Bonventre, JV TI Inducible nitric oxide synthase is an important contributor to ischemic preconditioning in the mouse kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 549A EP 549A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502693 ER PT J AU Dember, LM Holmberg, EF Kaufman, JS AF Dember, LM Holmberg, EF Kaufman, JS TI Randomized controlled trial of prophylactic repair of Hemodialysis arteriovenous (AV) graft stenosis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Renal Sect, Boston, MA 02118 USA. VA Boston Healthcare Syst, Renal Sect, Boston, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 600A EP 600A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502937 ER PT J AU Wolf, M Sandler, L Thadhani, R AF Wolf, M Sandler, L Thadhani, R TI Preeclampsia or gestational hypertension? The influence of systemic inflammation. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 608A EP 609A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502979 ER PT J AU Smirnakis, KV Wolf, M Thandhani, R AF Smirnakis, KV Wolf, M Thandhani, R TI Association between early-pregnancy microalbuminuria and insulin resistance. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 609A EP 609A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502981 ER PT J AU Wolf, M Ecker, J Thadhani, R AF Wolf, M Ecker, J Thadhani, R TI Insulin resistance: A recurring theme in the hypertensive disorders of pregnancy. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Obstet Unit, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 609A EP 609A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502980 ER PT J AU Knight, EL Ofsthun, N Teng, M Lazarus, JM Curhan, GC AF Knight, EL Ofsthun, N Teng, M Lazarus, JM Curhan, GC TI The impact of self-reported physical functioning on mortality in patients on hemodialysis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Fresenius Med Care, Lexington, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 626A EP 626A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503063 ER PT J AU Knight, EL Stampfer, MJ Hankinson, SE Curhan, GC AF Knight, EL Stampfer, MJ Hankinson, SE Curhan, GC TI The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 629A EP 630A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503078 ER PT J AU Thadhani, R Cheriyan, R Brenner, R Ford, J Powers, K Rahman, SN AF Thadhani, R Cheriyan, R Brenner, R Ford, J Powers, K Rahman, SN TI Treatment of anemia with Aranesp (TM) (darbepoetin alfa) improves health related quality of life (HRQOL) in patients with chronic kidney disease (CKD). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Houston, TX USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Virginia Nephrol Grp, Fairfax, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 637A EP 637A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503113 ER PT J AU Aaronson, ML Cornell, LD AF Aaronson, ML Cornell, LD TI Tolerability of high dose (500 mg) intravenous iron sucrose in pre-dialysis patients receiving either erythropoietin or daibepoetin. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MeritCare Med Ctr, Fargo, ND USA. Massachusetts Gen Hosp, Boston, MA 02114 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 641A EP 642A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503134 ER PT J AU Jones, CA Ficociello, LH Palecek, BE Silva, KH Warram, JW Krolewski, AS AF Jones, CA Ficociello, LH Palecek, BE Silva, KH Warram, JW Krolewski, AS TI Does loss of renal function occur before the onset of microalbuminuria in type 1 diabetes? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 645A EP 645A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503150 ER PT J AU Campoy, S Spiegel, DM Chonchol, MB AF Campoy, S Spiegel, DM Chonchol, MB TI Pre-end stage renal disease care improves outcomes at the start of hemodialysis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Denver Vet Affairs Med Ctr, Sect Renal Dis & Hypertens, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Denver, CO 80202 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 673A EP 673A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503288 ER PT J AU Cizman, B Waldman, M Tomaszewski, JE AF Cizman, B Waldman, M Tomaszewski, JE TI Collapsing glomerulopathy with acute renal failure (ARF) associated with interferon-alpha treatment for chronic hepatitis B. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Renal Sect, Philadelphia, PA 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 679A EP 679A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503317 ER PT J AU Johansen, KL Doyle, J Shubert, T Sakkas, GK Kent-Braun, JA AF Johansen, KL Doyle, J Shubert, T Sakkas, GK Kent-Braun, JA TI Mechanisms of skeletal muscle fatigue in patients on dialysis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. No Calif Inst Res & Educ, San Francisco, CA USA. Univ Massachusetts, Dept Exercise Sci, Amherst, MA 01003 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 700A EP 700A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503421 ER PT J AU Wolf, M Sandler, L Thadhani, R AF Wolf, M Sandler, L Thadhani, R TI Systemic inflammation: A bridge between preeclampsia and future atherosclerosis? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 728A EP 728A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503556 ER PT J AU Goruppi, S Bonventre, JV Kyriakis, JM AF Goruppi, S Bonventre, JV Kyriakis, JM TI Signaling pathways and late-onset gene induction associated with renal mesangial cell hypertrophy. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Res Labs, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 738A EP 738A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503603 ER PT J AU Watschinger, B Pascual, M AF Watschinger, B Pascual, M TI Capillary C4d deposition as a marker of humoral immunity in renal allograft rejection SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID PATHOLOGICAL FEATURES; CROSS-MATCH; INDIRECT ALLORECOGNITION; PERITUBULAR CAPILLARIES; TRANSPLANT RECIPIENTS; INDIRECT RECOGNITION; COMPLEMENT FRAGMENT; MEDIATED REJECTION; ANTIBODY; RESCUE C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Vienna, Dept Internal Med 3, Div Nephrol, Vienna, Austria. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Box MZ 70,Fruit St, Boston, MA 02114 USA. NR 38 TC 35 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 IS 9 BP 2420 EP 2423 DI 10.1097/01.ASN.0000029941.34837.22 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 588EA UT WOS:000177687000026 PM 12191988 ER PT J AU Liang, MH Mandl, LA Costenbader, K Fox, E AF Liang, MH Mandl, LA Costenbader, K Fox, E TI Atherosclerotic vascular disease in systemic lupus erythematosus SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE vascular disease; lupus; SLE ID CORONARY-ARTERY DISEASE; RISK-FACTORS; MYOCARDIAL-INFARCTION; HEART-DISEASE; ANTIPHOSPHOLIPID ANTIBODIES; LIPOPROTEIN LP(A); CHOLESTEROL; WOMEN; PREVALENCE; HOMOCYSTEINE AB In the United States, systemic lupus erythematosus (S,LE) disproportionately affects African Americans. It has become a chronic disease with long-term morbidity including chronic renal disease, osteoporosis, cataracts, psychosocial impairment, and importantly, atherosclerotic vascular disease (ASVD). The latter (myocardial infarction, angina, peripheral vascular disease and stroke) are strikingly accelerated, occurring in subjects who are predominantly premenopausal women at an age when ASVD is rare or unusual. Although much is known about the biology, risk factors, and the prevention of atherosclerosis in normal individuals, little work has been done in SLE. In fact, ASVD in people with SLE may be a, different disease.. Approximately 1.5% of SLE patients per year will have a myocardial infarction or equivalent; about 0.5% of SLE patients per year will have a stroke. The risk factors for ASVD in SLE are based on small, retrospective, single center studies. These suggest that the risk factors known for the general population (i.e., smoking, obesity, sedentary lifestyle, high LDL cholesterol, etc.) are also observed in SLE. The best study of risk factors shows that even accounting for the known factors, SLE and/or its treatment (glucocorticoids) is by far the most, important. Our current management of cardiovascular risk factors in SLE patients with ASVD is substandard and our adherence to national guidelines for prevention is substandard. It is not known whether improving either will prevent these disastrous outcomes. Very little is known about the risk factors in African Americans with SLE, although there is data to suggest that they may not be identical to those seen in Caucasian populations. The study of the best and most effective means to prevent ASVD in SLE and in African Americans with SLE and in African Americans with SLE should be a major priority. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02114 USA. RP Liang, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02114 USA. FU NIAMS NIH HHS [K08 AR02074-0, P01 AR36308] NR 43 TC 11 Z9 12 U1 1 U2 2 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD SEP PY 2002 VL 94 IS 9 BP 813 EP 819 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 602WV UT WOS:000178528200008 PM 12392045 ER PT J AU Finn, AV Gold, HK Tang, A Weber, DK Wight, TN Clermont, A Virmani, R Kolodgie, FD AF Finn, AV Gold, HK Tang, A Weber, DK Wight, TN Clermont, A Virmani, R Kolodgie, FD TI A novel rat model of carotid artery stenting for the understanding of restenosis in metabolic diseases SO JOURNAL OF VASCULAR RESEARCH LA English DT Article DE extracellular matrix; proliferation; rat; restenosis; stent ID SMOOTH-MUSCLE CELLS; NEOINTIMAL FORMATION; BALLOON ANGIOPLASTY; INSULIN-RESISTANCE; DIABETES-MELLITUS; TISSUE-RESPONSE; PORCINE MODEL; INJURY; PROLIFERATION; IMPLANTATION AB The effects of risk modifiers such as diabetes, obesity and hypertension on vascular healing after stent deployment are largely unknown, because of a lack of an appropriate animal model to study. Since many inbred strains of rats expressing these phenotypes are available, we validated a carotid artery model of in-stent restenosis in the rat. A detailed histomorphometric analysis was performed on 2-cell Multi-Link(TM) stents (1.5 x 5 mm) deployed in the common carotid artery of male Wistar rats. Early focal thrombus formation around stent struts with adherent leukocytes was evident by day 3. The number of ED-1-positive macrophages was maximal by day 7 and declined markedly thereafter. Neointimal cell proliferation peaked by day 7 (19.3 +/- 6.9) and progressively decreased to <2% by day 60. By day 14, neointimal area was significantly increased (0.39 +/- 0.03 vs. 0.18 +/-0.05 mm(2) at day 7, p = 0.003) characterized by an enhanced number of α-actin-positive smooth muscle cells surrounded by extracellular matrix rich in versican and hyaluronan. At day 28, neointimal area was maximal accompanied by an appreciable decrease in the staining intensity for hyaluronan and versican. By day 60, neointimal area decreased significantly (0.28 +/- 0.04 vs. 0.45 +/- 0.07 mm(2) at day 28, p = 0.04) independent of a change in cell density. This regression phase was accompanied by a marked increase in elastin fibrils and Collagen type 1. In summary, vascular healing following carotid artery stenting in the rat parallels that of larger animals; however, it is accelerated relative to humans. Copyright (C) 2002 S. Karger AG, Basel. C1 Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Washington, DC 20306 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hope Heart Inst, Seattle, WA USA. RP Kolodgie, FD (reprint author), Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Bldg 54,Room 2005,6825 16th St NW, Washington, DC 20306 USA. NR 36 TC 41 Z9 41 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD SEP-OCT PY 2002 VL 39 IS 5 BP 414 EP 425 DI 10.1159/000064518 PG 12 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 601CP UT WOS:000178428800004 PM 12297704 ER PT J AU Lin, PH Bush, RL Chaikof, EL Chen, CY Conklin, B Terramani, TT Brinkman, WT Lumsden, AB AF Lin, PH Bush, RL Chaikof, EL Chen, CY Conklin, B Terramani, TT Brinkman, WT Lumsden, AB TI A prospective evaluation of hypogastric artery embolization in endovascular aortoiliac aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Southern-Association-for-Vascular-Surgery CY JAN 16-19, 2002 CL MIAMI BEACH, FLORIDA SP SO Assoc Vasc Surg ID INTERNAL ILIAC ARTERY; ABDOMINAL AORTIC-ANEURYSMS; COIL EMBOLIZATION; REVASCULARIZATION; IMPOTENCE; SURGERY AB Purpose. Hypogastric artery embolization (HAE) is often performed in endovascular aortoiliac aneurysm repair to prevent potential endoleak, and this can be associated with pelvic ischemic sequelae. This prospective study was performed to evaluate the clinical outcome of HAE in patients who underwent endovascular aortoiliac aneurysm repair. Methods: During a 15-month period, 12 patients who underwent either unilateral or bilateral HAE for endovascular aortoiliac aneurysm repair were prospectively evaluated. All patients underwent preoperative and postoperative penile pressure measurement and pulse-volume recording evaluation. Angiographic features relating to pelvic collaterals and clinical outcomes relating to pelvic ischemia were evaluated. Results. Unilateral HA-E was performed in eight patients (67%), and bilateral HAE was performed in four patients (33%). Mean reductions in penile brachial index (PBI) after unilateral and bilateral HAE were 13 +/- 6% (not significant) and 39 +/- 14% (P < .05), respectively. Erectile dysfunction occurred in three patients for unilateral HAE (38%) and in two patients for bilateral HAE (50%), with an overall PBI reduction of 36 &PLUSMN; 12% (P < .01). No significant change in thigh brachial or ankle brachial index occurred after HAE. Hip and buttock claudication occurred in four patients for unilateral HAE (50%) and in two patients for bilateral HAE (50%), with an overall PBI reduction of 18 +/- 9% (P < .05). Other associated pelvic ischemic complications after bilateral HAE included one scrotal skin sloughing (25%) that occurred 3 days after aortic endografting and one sacral decubitus (25%) that occurred 4 months after aortic endografting. With analysis of angiographic collateral patterns, diseased profunda femoral artery (PFA; >50% stenosis) was noted in four patients, all in whom post-HAE pelvic ischemic symptoms developed (P < .05). In contrast, only four of the remaining eight patients with normal or mild PFA disease had pelvic ischemic sequelae after HAE. Conclusion: Erectile dysfunction after HAE correlates with significant reduction in PBI. Severe pelvic ischemic symptoms are more likely to occur after bilateral HAE, which should be avoided if possible. Moreover, patients with diseased PFA are at risk of development of pelvic ischemia after HAE. Our data suggest a potential role of concomitant profundapalsty at the time of aortic endografting to improve pelvic collateral flow and reduce pelvic ischemia in this subset of patients with HAE. C1 Baylor Coll Med, Houston VAMC, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. RP Lin, PH (reprint author), Baylor Coll Med, Houston VAMC, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, 2002 Holcomb Blvd 112, Houston, TX 77030 USA. NR 21 TC 69 Z9 77 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2002 VL 36 IS 3 BP 500 EP 505 DI 10.1067/mva.2002.127350 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 595GE UT WOS:000178099600021 PM 12218973 ER PT J AU Contreras, AM Hiasa, Y He, WP Terella, A Schmidt, EV Chung, RT AF Contreras, AM Hiasa, Y He, WP Terella, A Schmidt, EV Chung, RT TI Viral RNA mutations are region specific and increased by ribavirin in a full-length hepatitis C virus replication system SO JOURNAL OF VIROLOGY LA English DT Article ID HYPERVARIABLE REGION-1; GENETIC-HETEROGENEITY; INTERFERON THERAPY; EXPRESSION SYSTEM; POLYMERASE; EVOLUTION; CHIMPANZEE; STABILITY; SEQUENCE; ALPHA AB High rates of genetic variation ensure the survival of RNA viruses. Although this variation is thought to result from error-prone replication, RNA viruses must also maintain highly conserved genomic segments. A balance between conserved and variable viral elements is especially important in order for viruses to avoid "error catastrophe." Ribavirin has been shown to induce error catastrophe in other RNA viruses. We therefore used a novel hepatitis C virus (HCV) replication system to determine relative mutation frequencies in variable and conserved regions of the HCV genome, and we further evaluated these frequencies in response to ribavirin. We sequenced the 5' untranslated region (5' UTR) and the core, E2 HVR-1, NS5A, and NS5B regions of replicating HCV RNA isolated from cells transfected with a T7 polymerase-driven full-length HCV cDNA plasmid containing a cis-acting hepatitis delta virus ribozyme to control 3' cleavage. We found quasispecies in the E2 HVR-1 and NS5B regions of untreated replicating viral RNAs but not in conserved 5' UTR, core, or NS5A regions, demonstrating that important cis elements regulate mutation rates within specific viral segments. Neither T7-driven replication nor sequencing artifacts produced these nucleotide substitutions in control experiments. Ribavirin broadly increased error generation, especially in otherwise invariant regions, indicating that it acts as an HCV RNA mutagen in vivo. Similar results were obtained in hepatocyte-derived cell lines. These results demonstrate the potential utility of our system for the study of intrinsic factors regulating genetic variation in HCV. Our results further suggest that ribavirin acts clinically by promoting nonviable HCV RNA mutation rates. Finally, the latter result suggests that our replication model may be useful for identifying agents capable of driving replicating virus into error catastrophe. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. FU NIA NIH HHS [R01 AG043478]; NIAID NIH HHS [R01 AI43478]; NIDDK NIH HHS [R01 DK057857, R01 DK 57857] NR 35 TC 142 Z9 145 U1 0 U2 6 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 SEP PY 2002 VL 76 IS 17 BP 8505 EP 8517 DI 10.1128/JVI.76.17.8505-8517.2002 PG 13 WC Virology SC Virology GA 582DR UT WOS:000177334900001 PM 12163570 ER PT J AU Yu, XG Addo, MM Rosenberg, ES Rodriguez, WR Lee, PK Fitzpatrick, CA Johnston, MN Strick, D Goulder, PJR Walker, BD Altfeld, M AF Yu, XG Addo, MM Rosenberg, ES Rodriguez, WR Lee, PK Fitzpatrick, CA Johnston, MN Strick, D Goulder, PJR Walker, BD Altfeld, M TI Consistent patterns in the development and immunodominance of human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T-cell responses following acute HIV-1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURED TREATMENT INTERRUPTIONS; IMMUNE-RESPONSES; LYMPHOCYTE RESPONSES; VACCINE DESIGN; HLA-B; VIREMIA; EPITOPES; CTL; INDIVIDUALS; ESCAPE AB Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T-cell responses generated during acute infection play a critical role in the initial control of viremia. However, little is known about the viral T-cell epitopes targeted during acute infection or about their hierarchy in appearance and relative immunodominance over time. In this study, HIV-1-specific CD8(+) T-cell responses in 18 acutely infected individuals expressing HLA-A3 and/or -B7 were characterized. Detailed analysis of CD8 responses in one such person who underwent treatment of acute infection followed by reexposure to HIV-1 through supervised treatment interruptions (STI) revealed recognition of only two cytotoxic T-lymphocyte (CTL) epitopes during symptomatic acute infection. HIV-1-specific CD8(+) T-cell responses broadened significantly during subsequent exposure to the virus, ultimately targeting 27 distinct CTL epitopes, including 1.5 different CTL epitopes restricted by a single HLA class I allele (HLA-A3). The same few peptides were consistently targeted in an additional 17 persons expressing HLA-A3 and/or -B7 during acute infection. These studies demonstrate a consistent pattern in the development of epitope-specific responses restricted by a single HLA allele during acute HIV-1 infection, as well as persistence of the initial pattern of immunodominance during subsequent STI. In addition, they demonstrate that HIV-1-specific CD8(+) T-cell responses can ultimately :target a previously unexpected and unprecedented number of epitopes in a single infected individual; even though these are not detectable during the initial exposure to virus. These studies have important implications for vaccine design and evaluation. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. RP Altfeld, M (reprint author), Massachusetts Gen Hosp E, CNY 5212, 149 13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI040873, R01 AI050429, R01 AI40873, R01 AI50429, R37 AI125568, R01 AI030914, R01 AI044656, R01 AI30914, R01 AI44656] NR 48 TC 111 Z9 115 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2002 VL 76 IS 17 BP 8690 EP 8701 DI 10.1128/JVI.76.17.8690-8701.2002 PG 12 WC Virology SC Virology GA 582DR UT WOS:000177334900020 PM 12163589 ER PT J AU Yusim, K Kesmir, C Gaschen, B Addo, MM Altfeld, M Brunak, S Chigaev, A Detours, V Korber, BT AF Yusim, K Kesmir, C Gaschen, B Addo, MM Altfeld, M Brunak, S Chigaev, A Detours, V Korber, BT TI Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation SO JOURNAL OF VIROLOGY LA English DT Article ID MHC CLASS-I; VACCINE DESIGN; CTL EPITOPE; CD8(+) LYMPHOCYTES; VIRAL REPLICATION; DENDRITIC CELLS; RESPONSES; INFECTION; ESCAPE; NEF AB The human cytotoxic T-lymphocyte (CTL) response to human immunodeficiency virus type 1 (HIV-1) has been intensely studied, and hundreds of CTL epitopes have been experimentally defined, published, and compiled in the HIV Molecular Immunology Database. Maps of CTL epitopes on HIV-1 protein sequences reveal that defined epitopes tend to cluster. Here we integrate the global sequence and immunology databases to systematically explore the relationship between HIV-1 amino acid sequences and CTL epitope distributions. CTL responses to five HIV-1 proteins, Gag p17, Gag p24, reverse transcriptase (RT), Env, and Nef, have been particularly well characterized in the literature to date. Through comparing CTL epitope distributions in these five proteins to global protein sequence alignments, we identified distinct characteristics of HIV amino acid sequences that correlate with CTL epitope localization. First, experimentally defined HIV CTL epitopes are concentrated in relatively conserved regions. Second, the highly variable regions that lack epitopes bear cumulative evidence of past immune escape that may make them relatively refractive to CTLs: a paucity of predicted proteasome processing sites and an enrichment for amino acids that do not serve as C-terminal anchor residues. Finally, CTL epitopes are more highly concentrated in alpha-helical regions of proteins. Based on amino acid sequence characteristics, in a blinded fashion, we predicted regions in HIV regulatory and accessory proteins that would be likely to contain CTL epitopes; these predictions were then validated by comparison to new sets of experimentally defined epitopes in HIV-1 Rev, Tat, Vif, and Vpr. C1 Los Alamos Natl Lab, HIV Sequence Database, Los Alamos, NM 87545 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Univ Utrecht, Theoret Biol Grp, NL-3584 CH Utrecht, Netherlands. Tech Univ Denmark, Bioctr DTU, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. RP Korber, BT (reprint author), Los Alamos Natl Lab, HIV Sequence Database, Mail Stop K710, Los Alamos, NM 87545 USA. RI Chigaev, Alexandre/A-3103-2010; Kesmir, Can/B-9410-2011; OI Chigaev, Alexandre/0000-0002-7726-638X; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [R01 AI050429, R01 AI50429] NR 67 TC 201 Z9 208 U1 2 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 SEP PY 2002 VL 76 IS 17 BP 8757 EP 8768 DI 10.1128/JVI.76.17.8757-8768.2002 PG 12 WC Virology SC Virology GA 582DR UT WOS:000177334900027 PM 12163596 ER PT J AU Hooker, K Bowman, SR Coehlo, DP Lim, SR Kaye, J Guariglia, R Li, FZ AF Hooker, K Bowman, SR Coehlo, DP Lim, SR Kaye, J Guariglia, R Li, FZ TI Behavioral change in persons with dementia: Relationships with mental and physical health of caregivers SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC INVENTORY; FAMILY CAREGIVERS; SPOUSE-CAREGIVERS; STRESS; INSTITUTIONALIZATION; PSYCHOPATHOLOGY; PREDICTORS; DEPRESSION; MORTALITY AB The purpose of this study was to examine the effects that changes in behavioral and psychological symptoms of dementia of persons with Alzheimer's disease have on their caregivers' mental health and physical health. The research design was a prospective, longitudinal follow-up study conducted in a major medical center and in participants' homes. Longitudinal analysis linking change in behavior to caregiver outcomes was based on 64 cases. Care recipients were assessed at the time of diagnosis with the Mini-Mental State Examination (MMSE). To provide information on the care recipient's behaviors, caregivers participated in an interview with the Modified Neuropsychiatric Inventory at diagnosis and at follow-up. Caregivers also completed a battery of established instruments to measure stress appraisal, mental health, and perceptions of their physical health at follow-up. Results showed that increases in problem behaviors among persons living with dementia, along with residence status, were significant predictors of caregivers' mental health and also their physical health. However, these relationships were mediated through stress appraisal. Variables such as MMSE score of the person with dementia, number of years caregiving, relationship status, and education level were not significant predictors of caregivers' health when behavior change was in the model. C1 Oregon State Univ, Dept Human Dev & Family Sci, Corvallis, OR 97331 USA. Oregon Hlth & Sci Univ, Oregon Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Res Inst, Eugene, OR 97403 USA. RP Hooker, K (reprint author), Oregon State Univ, Dept Human Dev & Family Sci, Milam 322, Corvallis, OR 97331 USA. EM hookerk@orst.edu FU NIA NIH HHS [P30 AG 08017] NR 52 TC 34 Z9 34 U1 3 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD SEP PY 2002 VL 57 IS 5 BP P453 EP P460 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 589NU UT WOS:000177766800008 PM 12198104 ER PT J AU Shlipak, MG Fried, LF Crump, C Bleyer, AJ Manolio, TA Tracy, RP Furberg, CD Psaty, BM AF Shlipak, MG Fried, LF Crump, C Bleyer, AJ Manolio, TA Tracy, RP Furberg, CD Psaty, BM TI Cardiovascular disease risk status in elderly persons with renal insufficiency SO KIDNEY INTERNATIONAL LA English DT Article DE coronary heart disease; stroke; age and cardiovascular disease; risk predictors; serum creatinine; subclinical heart disease; kidney insufficiency; chronic renal disease ID NUTRITION EXAMINATION SURVEY; BLOOD-PRESSURE INDEX; 3RD NATIONAL-HEALTH; SERUM CREATININE; KIDNEY-DISEASE; OLDER ADULTS; MORTALITY; HYPERTENSION; DYSFUNCTION; PREDICTION AB Background. Renal insufficiency has been independently associated with incident cardiovascular disease events in some, but not all, prospective studies. We determined the prevalence of elevated cardiovascular disease risk status among elderly persons with renal insufficiency. Methods. This study is a cross-sectional analysis using data collected at the baseline visit of the Cardiovascular Health Study, which enrolled 5888 community dwelling adults aged 65 years or older from four clinical centers in the United States. Renal insufficiency was defined as a serum creatinine level greater than or equal to1.3 mg/dL in women and greater than or equal to1.5 mg/dL in men. The outcomes of this study included prevalent cardiovascular disease [prior coronary heart disease (CHD) or stroke], subclinical cardiovascular disease (abnormal values of ankle-arm index, carotid ultrasound, and echocardiography) and elevated cardiovascular risk based upon a diagnosis of diabetes and the Framingham equations. The association between renal insufficiency and cardiovascular risk status was estimated with and without adjustment for other cardiovascular predictors. Results. Among the 5808 participants with creatinine levels measured at entry, 15.9% of men (N = 394), and 7.6% of women (N = 254) had renal insufficiency. The prevalence of either clinical or subclinical cardiovascular disease was 64% in persons with renal insufficiency compared with 43% in those without it [odds ratio (OR) 2.34; 95 % confidence interval (95 % CI), 1.96, 2.80]. After adjustment for other cardiovascular risk factors, renal insufficiency remained significantly associated with clinical and subclinical cardiovascular disease (adjusted OR 1.43; 95% CI, 1.18,1.75), but the magnitude of association was substantially reduced. After combining clinical and subclinical cardiovascular disease, diabetes, and an estimated risk >20% by the Framingham equations, 78% of men and 61% of women with renal insufficiency had elevated cardiovascular risk status. Conclusions. Renal insufficiency is a marker for elevated cardiovascular disease risk in community dwelling elderly adults. C1 Vet Affairs Med Ctr, Med Serv, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Winston Salem, NC USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Pathol & Biochem, Burlington, VT USA. RP Shlipak, MG (reprint author), Vet Affairs Med Ctr, Med Serv, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [N01 HC 85079, N01 HC 85086, R03 HL 68099-01, N01 HC 15103, N01 HC 35129] NR 30 TC 119 Z9 125 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 SEP PY 2002 VL 62 IS 3 BP 997 EP 1004 DI 10.1046/j.1523-1755.2002.00522.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 584WR UT WOS:000177492200030 PM 12164883 ER PT J AU Hooper, DC AF Hooper, DC TI Fluoropuinolone resistance among Gram-positive cocci SO LANCET INFECTIOUS DISEASES LA English DT Review ID COMMUNITY-ACQUIRED PNEUMONIA; COAGULASE-NEGATIVE STAPHYLOCOCCI; II TOPOISOMERASE MUTATIONS; MULTIDRUG EFFLUX PUMPS; INTENSIVE-CARE UNIT; IN-VITRO ACTIVITIES; STREPTOCOCCUS-PNEUMONIAE; FLUOROQUINOLONE RESISTANCE; DNA GYRASE; CIPROFLOXACIN RESISTANCE AB Resistance to fluoroquinolones among Gram-positive cocci has emerged as these antimicrobial agents have become extensively used in clinical medicine. Resistance is effected by changes in the bacterial target enzymes DNA gyrase and topoisomerase IV, which reduce drug binding, and by action of native bacterial membrane pumps that remove drug from the cell. In both cases, quinolone exposure selects for spontaneous mutants that are present in large bacterial populations, and which contain chromosomal mutations that alter the target protein or increase the level of pump expression. Resistance among clinical isolates has been greatest in Staphylococcus aureus and particularly among meticillin-resistant strains, in which both selection by quinolone exposure and transmission of clonal strains in health-care settings have contributed to high prevalence. Resistance in Streptococcus pneumoniae has also emerged in the community. Fluoroquinolone resistance has arisen in multidrug-resistant clones and its prevalence has been especially high in Hong Kong and Spain. Further spread and selection of such resistance could compromise the utility of a valuable class of antimicrobial agents, a point that emphasises the importance of the careful use of these agents in appropriate patients and doses, as well as careful infection-control practices. C1 Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med,Infect Control Unit, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med,Infect Control Unit, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI023988] NR 118 TC 179 Z9 187 U1 1 U2 9 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2002 VL 2 IS 9 BP 530 EP 538 DI 10.1016/S1473-3099(02)00369-9 PG 9 WC Infectious Diseases SC Infectious Diseases GA 589LD UT WOS:000177759100018 PM 12206969 ER PT J AU Coates, AS Goldhirsch, A Gelber, RD AF Coates, AS Goldhirsch, A Gelber, RD CA Int Breast Canc Study Grp TI Overhauling the breast cancer overview: are subsets subversive? SO LANCET ONCOLOGY LA English DT Editorial Material C1 Canc Council Australia, Sydney, NSW 2001, Australia. European Inst Oncol, Milan, Italy. Oncol Inst So Switzerland, Lugano, Switzerland. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Coates, AS (reprint author), Canc Council Australia, GPO Box 4708, Sydney, NSW 2001, Australia. NR 6 TC 14 Z9 14 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2002 VL 3 IS 9 BP 525 EP 526 DI 10.1016/S1470-2045(02)00842-2 PG 2 WC Oncology SC Oncology GA 591RT UT WOS:000177894600016 PM 12217786 ER PT J AU Ung, F Rocco, JW Deschler, DG AF Ung, F Rocco, JW Deschler, DG TI Temporary Intraoperative external fixation in mandibular reconstruction 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 DE external fixation; vascularized bone graft; free tissue transfer; mandible ID FREE FLAPS; BONY AB Objectives: To describe the use of a temporary intraoperative external fixation device to assist in the optimal bony reconstruction of the mandible in the setting of vascularized bone grafts. Study Design: A retrospective review of six patients who underwent composite resection of the mandible and subsequent reconstruction with osteocutaneous free tissue transfer in a tertiary care center. Methods: Six cases of mandibular reconstruction using an intraoperative external fixation system to assist the positioning of vascularized bone grafts are presented. All patients had composite resection of the mandible and subsequent reconstruction with either a scapula or fibula osteocutaneous flap. Follow-up ranged from 2 to 16 months. Results: Successful reconstruction as defined by acceptable contour, occlusion, and condylar position was achieved in all cases. Complications were limited to a postoperative cerebrovascular accident requiring anticoagulation and subsequent neck hematoma. Conclusions: Use of intraoperative external fixation maintains the proper alignment of mandibular segments without the use of a bridging reconstruction plate. This technique is particularly valuable with tumors involving the outer cortex of the mandible. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 8 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2002 VL 112 IS 9 BP 1569 EP 1572 DI 10.1097/00005537-200209000-00006 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 592KT UT WOS:000177937400006 PM 12352664 ER PT J AU Munshi, NC Tricot, G Desikan, R Badros, A Zangari, M Toor, A Morris, C Anaissie, E Barlogie, B AF Munshi, NC Tricot, G Desikan, R Badros, A Zangari, M Toor, A Morris, C Anaissie, E Barlogie, B TI Clinical activity of arsenic trioxide for the treatment of multiple myeloma SO LEUKEMIA LA English DT Article DE arsenic trioxide; antiangiogenesis; apoptosis; multiple myeloma ID ACUTE PROMYELOCYTIC LEUKEMIA; AUTOLOGOUS BONE-MARROW; HIGH-DOSE THERAPY; GROWTH-INHIBITION; FOLLOW-UP; APOPTOSIS; INDUCTION; CELLS AB Arsenic has been used since ancient times as a therapeutic agent. However, until recently its use in modern medicine has been restricted to the treatment of a limited number of parasitic infections. In the early 1990s, reports from China described impressive results with arsenic trioxide in patients with de novo, relapsed, and refractory acute promyelocytic leukemia (APL). Other investigators subsequently confirmed these results leading to approval of its use for relapsed or refractory APL in the United States. Investigations of this agent have demonstrated that its efficacy in APL and preclinical tumor models is dependent upon a number of mechanisms, including induction of apoptosis, effects on cellular differentiation, cell cycling, and tumor angiogenesis. Subsequent preclinical studies showed significant activity of arsenic trioxide in multiple myeloma (MM). Based on this, in a phase II trial, we have evaluated the activity of arsenic trioxide in 14 patients with relapsed MM, refractory to conventional salvage therapy. With the dose and schedule used, treatment with arsenic trioxide produced responses in three patients and prolonged stable disease in a fourth patient, with the longest response lasting 6 weeks. Although treatment was reasonably well tolerated, in these patients with extensive prior therapy, 11 developed cytopenia, five associated with infectious complications and three developed deep vein thromboses. The results of this small trial support further investigation of this novel drug for the treatment of patients with relapsed or refractory MM. C1 Univ Arkansas Med Sci, Myeloma & Transplantat Med Ctr, Little Rock, AR 72205 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. Loyola Univ, Chicago, IL 60611 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 44 Binney St,M557, Boston, MA 02115 USA. NR 17 TC 100 Z9 103 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 2002 VL 16 IS 9 BP 1835 EP 1837 DI 10.1038/sj.leu.2402599 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 593XF UT WOS:000178019200035 PM 12200700 ER PT J AU Dong, HY Shahsafaei, A Dorfman, DM AF Dong, HY Shahsafaei, A Dorfman, DM TI CD148 and CD27 are expressed in B cell lymphomas derived from both memory in naive B cells SO LEUKEMIA & LYMPHOMA LA English DT Article DE non-Hodgkin's lymphoma; chronic lymphocytic leukemia/small lymphocytic lymphoma; mantle cell lymphoma; marginal zone lymphoma ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PROTEIN-TYROSINE-PHOSPHATASE; VARIABLE REGION GENES; TUMOR-NECROSIS-FACTOR; V-H GENES; SOMATIC HYPERMUTATION; ANTIGEN; CLASSIFICATION; ACTIVATION; MOLECULES AB CD148 and CD27 are activation antigens involved in B cell and T cell activation and development. They have been recently proposed as markers of normal human memory B cells corresponding to the presence of somatically hypermutated IgV genes. We undertook an immunohistochemical study of CD148 and CD27 expression on neoplastic B cells in 116 cases of B cell non-Hodgkin's lymphoma. All cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma, Burkitt's lymphoma, and the vast majority of cases of marginal zone B cell lymphoma and most cases of plasmacytoma/myeloma expressed CD148 and CD27. Follicular lymphoma and diffuse large B cell lymphoma were also immunoreactive for CD148 and CD27 with some variation and discordance in expression. Cases of precursor B-lymphoblastic lymphoma/leukemia did not express CD148 or CD27. Our findings demonstrate that CD148 and CD27 are expressed in a wide range of B cell non-Hodgkin's lymphomas, and, therefore, do not serve to distinguish between neoplastic cells of naive and memory B cell derivation. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Dorfman, DM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [T32CA-09216 D20] NR 27 TC 23 Z9 23 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP PY 2002 VL 43 IS 9 BP 1855 EP 1858 DI 10.1080/1042819021000006385 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 587VD UT WOS:000177663400022 PM 12685844 ER PT J AU Keller, SM Vangel, MG Adak, S Wagner, H Schiller, JH Herskovic, A Komaki, R Perry, MC Marks, RS Livingston, RB Johnson, DH AF Keller, SM Vangel, MG Adak, S Wagner, H Schiller, JH Herskovic, A Komaki, R Perry, MC Marks, RS Livingston, RB Johnson, DH TI The influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer SO LUNG CANCER LA English DT Article DE gender; non-small cell lung cancer; adjuvant therapy ID SEX-ASSOCIATED DIFFERENCES; RANDOMIZED TRIAL; WOMEN; RISK; SMOKERS; SMOKING; TABLES; MEN AB This study evaluates the influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer (NSCLC). The Eastern Cooperative Oncology Group conducted a randomized prospective trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC. A laboratory correlative study assessed the prevalence and prognostic significance of p53 and K-ras mutations. Patients were randomized to receive either radiotherapy (RT) alone or four cycles of cisplatin and VP-16 administered concurrently with radiotherapy (CRT). Median survival was 35 months for the 28 5 men and 41 months for the 203 women enrolled in the study (P = 0.12). The relative risk (RR) of death for men vs women was 1.19 (95% confidence interval [CI], 0.95-1.49). Median survival of the 147 men and 95 women randomized to the RT arm was 39 months each (P = 0.35). Median survival of the 138 men and 108 women randomized to the CRT arm was 30 and 42 months, respectively (P = 0.18). Disease recurrence patterns were similar between the genders. Univariate and multivariate analyses demonstrated improved survival for women with tumors of non-squamous histology (P < 0.01). The distribution of p53 and K-ras mutations was similar between the genders and had no influence on survival. Gender does not influence survival following adjuvant RT or CRT administered to patients with completely resected stages II and IIIa NSCLC. However, women with non-squamous histology have increased survival when compared to men. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Montefiore Med Ctr, Dept Cardiothorac Surg, Bronx, NY 10467 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. H Lee Moffitt Canc Ctr & Res Inst, Dept Radiat Oncol, Tampa, FL USA. Univ Wisconsin, Med Oncol Sect, Madison, WI USA. Oakwood Hosp, Dept Radiat Oncol, Detroit, MI USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX USA. Univ Missouri, Ellis Fischel Canc Ctr, Div Hematol & Med Oncol, Columbia, MO USA. Mayo Clin, Dept Med Oncol, Rochester, MN USA. Univ Washington, Div Med Oncol, Seattle, WA USA. Vanderbilt Univ, Div Med Oncol, Nashville, TN USA. RP Montefiore Med Ctr, Dept Cardiothorac Surg, 3400 Bainbridge Ave,Suite 5B, Bronx, NY 10467 USA. EM skeller@montefiore.org RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA14958, CA20319, CA21076, CA21115, CA21661, CA23318, CA25224, CA49957, CA66636, CA73590] NR 23 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD SEP PY 2002 VL 37 IS 3 BP 303 EP 309 AR PII S0169-5002(02)00103-4 DI 10.1016/S0169-5002(02)00103-4 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 602EZ UT WOS:000178494000010 PM 12234700 ER PT J AU Cheng, LL Newell, K Mallory, AE Hyman, BT Gonzalez, RG AF Cheng, LL Newell, K Mallory, AE Hyman, BT Gonzalez, RG TI Quantification of neurons in Alzheimer and control brains with ex vivo high resolution magic angle spinning proton magnetic resonance spectroscopy and stereology SO MAGNETIC RESONANCE IMAGING LA English DT Article DE NAA (N-acetylaspartate); Alzheimer disease; superior temporal sulcus; stereology; high resolution magic angle spinning proton MRS ID H-1 MRS; NEUROFIBRILLARY TANGLES; DISEASE; DEMENTIA; NEUROPATHOLOGY AB Samples from human brains were examined with both stereologic methods for neuronal counting and high resolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy (1HMRS) for quantification of cellular metabolites. A statistically significant linear correlation between neuronal density and the concentration of N-acetylaspartate (NAA) in the superior temporal sulcus (STS) area was observed. Although NAA has been widely utilized as a neuronal marker in in vivo MRS, an emerging sub-discipline of diagnostic neuroradiology, the experimental proof of the unilateral relationship between NAA and neurons has yet to be confirmed. The observed correlation provides experimental evidence that NAA concentration is proportional to the neuronal density. Metabolite ratios measured from the STS area were compared to those from frontal association cortex for their sensitivities in differentiating Alzheimer disease brains from control brains. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Cheng, LL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. FU NCI NIH HHS [CA77727]; NCRR NIH HHS [RR13213]; NIA NIH HHS [AG08487, P01 AG05134]; NINDS NIH HHS [NS34626] NR 23 TC 46 Z9 54 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD SEP PY 2002 VL 20 IS 7 BP 527 EP 533 AR PII S0730-725X(02)00512-X DI 10.1016/S0730-725X(02)00512-X PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 613GJ UT WOS:000179124300003 PM 12413598 ER PT J AU Langenau, DM Palomero, T Kanki, JP Ferrando, AA Zhou, Y Zon, LI Look, AT AF Langenau, DM Palomero, T Kanki, JP Ferrando, AA Zhou, Y Zon, LI Look, AT TI Molecular cloning and developmental expression of Tlx (Hox11) genes in zebrafish (Danio rerio) SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Tlx-1; Tlx-3a; Tlx-3b; Tlx-a; Pax2.1; Krox20; narrowminded; zebrafish; cranial sensory ganglia; dorsal root ganglia; Rohon-Beard neurons; spleen ID CRANIAL SENSORY GANGLIA; HOMEOBOX GENE; MURINE HOMOLOG; NEURONS; ASSIGNMENT; MEGACOLON; EMBRYO; SPLEEN; MICE AB Tlx (Hox11) genes are orphan homeobox genes that play critical roles in the regulation of early developmental processes in vertebrates. Here, we report the identification and expression patterns of three members of the zebrafish Tlx family. These genes share similar, but not identical, expression patterns with other vertebrate Tlx-1 and Tlx-3 genes. Tlx-1 is expressed early in the developing hindbrain and pharyngeal arches, and later in the putative splenic primordium. However, unlike its orthologues, zebrafish Tlx-1 is not expressed in the cranial sensory ganglia or spinal cord. Two homologues of Tlx-3 were identified: Tlx-3a and Tlx-3b, which are both expressed in discrete regions of the developing nervous system, including the cranial sensory ganglia and Rohon-Beard neurons. However, only Tlx-3a is expressed in the statoacoustic cranial ganglia, enteric neurons and non-neural tissues such as the fin bud and pharyngeal arches and Tlx-3b is only expressed in the dorsal root ganglia. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA. RP Kanki, JP (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA68484] NR 21 TC 26 Z9 28 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 2002 VL 117 IS 1-2 BP 243 EP 248 AR PII S0925-4773(02)00187-9 DI 10.1016/S0925-4773(02)00187-9 PG 6 WC Developmental Biology SC Developmental Biology GA 598GT UT WOS:000178268200019 PM 12204264 ER PT J AU Karlawish, JHT Fox, E Pearlman, R AF Karlawish, JHT Fox, E Pearlman, R TI How changes in health care practices, systems, and research challenge the practice of informed consent SO MEDICAL CARE LA English DT Article DE informed consent; autonomy; evidence-based medicine ID OVARIAN-CANCER; MANAGED CARE; DECISIONS; CHOICE AB Informed consent has been the central model for ethical decision making in clinical care and research. The goal of informed consent is to protect the right of a competent person to make his or her own health care decisions based on personal values and goals. But changes in health care practices, systems, and research have challenged this well-established goal. This paper examines these changes to show that decisions about care and research directed to individual patients rely more and more upon a population perspective. As a result, efforts to promote patient choice should attend to the ethical decision-making processes of institutions that create and sustain this perspective. C1 Univ Penn, Hlth Syst, Dept Med, Div Geriatr Med,Ralston Penn Ctr, Philadelphia, PA 19104 USA. Univ Penn, Hlth Syst, Dept Med, Div Geriatr Med,Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. Univ Penn, Hlth Syst, Dept Med, Div Geriatr Med,Ctr Bioeth, Philadelphia, PA 19104 USA. Vet Hlth Adm, Natl Ctr Eth, White River Jct, VT USA. George Washington Univ, Washington, DC USA. Univ Washington, Div Gerontol & Geriat Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Div Gerontol & Geriat Med, Dept Med, Seattle, WA 98195 USA. RP Karlawish, JHT (reprint author), Univ Penn, Hlth Syst, Dept Med, Div Geriatr Med,Ralston Penn Ctr, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 38 TC 2 Z9 2 U1 3 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 SEP PY 2002 VL 40 IS 9 SU S BP 12 EP 19 DI 10.1097/01.MLR.0000023951.75030.51 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 591HU UT WOS:000177874300003 ER PT J AU Lee, ML Yano, EM Wang, MM Simon, BF Rubenstein, LV AF Lee, ML Yano, EM Wang, MM Simon, BF Rubenstein, LV TI What patient population does visit-based sampling in primary care settings represent? SO MEDICAL CARE LA English DT Article DE sampling; health surveys; process and outcomes assessment; primary care ID RANDOMIZED CONTROLLED TRIAL; MEDICAL-CARE; SCREENING INSTRUMENT; AMBULATORY CARE; HEALTH-CARE; OUTCOMES; QUESTIONNAIRE; RELIABILITY; EDUCATION; EMERGENCY AB BACKGROUND. Evaluations of outpatient interventions often rely on consecutive sampling of clinic visitors, and assume that study results generalize to the population of patients cared for. OBJECTIVE. The representativeness of such visit-based sampling compared with the population of patients seen during the same year, in terms of sociodemographic and clinical characteristics of the user groups that visit-based sampling yielded were assessed. METHODS. One thousand five hundred forty-six continuing patients visiting the primary care firms in an urban VA medical center were consecutively sampled, and visit frequencies were compared for these patients with subsets of the patient population. Administrative and survey data was then used to describe the types of patients visit-based sampling most represented compared with the types of patients sampled less frequently. RESULTS. The average sampled patient visited the firms significantly more often than patients in the reference population (18.7 vs. 9.5). Sampled patients were significantly older (>55 years), in poorer health (higher prevalence of cancer, stroke, hypertension), less likely to smoke, and more likely to be single than the average patient visiting the firms (P <0.05). Adjusting for age and sickness, frequent visitors were more apt to have experienced continuity of care during the prior year, to prefer VA care, and to be unemployed. CONCLUSIONS. Consecutive visit-based sampling actually selected patients with a visit pattern more typical of the patient population visiting four or more times a year. Studies using sampling of consecutive visitors will typically under-represent low users of care and should account for the degree to which results may not generalize to the broader practice population. C1 VA Greater Los Angeles HSR&D Ctr Excellence, Ctr Study Healthcare Provider Behav, VA Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. VA Greater Los Angeles Healthcare Syst, Nursing Home, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RAND Corp, Dept Social Policy, Santa Monica, CA 90406 USA. RP Lee, ML (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, Ctr Study Healthcare Provider Behav, VA Sepulveda Ambulatory Care Ctr, 152,16111 Plummer St, Sepulveda, CA 91343 USA. NR 50 TC 27 Z9 27 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 SEP PY 2002 VL 40 IS 9 BP 761 EP 770 DI 10.1097/01.MLR.0000024720.87446.41 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 589ZD UT WOS:000177790900006 PM 12218767 ER PT J AU Halpern, SD Ubel, PA Berlin, JA Asch, DA AF Halpern, SD Ubel, PA Berlin, JA Asch, DA TI Randomized trial of $5 versus $10 monetary incentives, envelope size, and candy to increase physician response rates to mailed questionnaires SO MEDICAL CARE LA English DT Article DE response rate; surveys; mailed questionnaire; bias; cost-effectiveness ID CONFIDENCE-INTERVALS; COST-EFFECTIVENESS AB BACKGROUND. The validity of the results of mailed surveys is often threatened by nonresponse bias, which is made more likely when response rates are low. However, the effectiveness and cost-effectiveness of several strategies to increase response rates are uncertain. OBJECTIVES. To assess three strategies to increase response rates to mailed physician surveys: including a $10 versus a $5 cash incentive in the initial mailing, including a mint candy or not, and using a large versus small outgoing envelope. RESEARCH DESIGN AND SUBJECTS. Using a 2 X 2 X 2 factorial design, a randomized trial of these strategies was conducted in a survey of 1200 physicians randomly selected from the American Medical Association's Master File. RESULTS. Including a $10 incentive yielded a significantly higher response rate (60.5% vs. 52.8%) (P = 0.009). The mailing and incentive costs per completed response were $12.24 (95% Cl, $11.75, $13.64) in the $5 group and $18.48 (95% Cl, $17.77, $20.69) in the $10 group. Each additional response obtained in the $10 group came at an incremental cost of $61.26 (95% Cl, $36.98, $200.80). Neither inclusion of a mint nor use of a large envelope influenced the response rate. CONCLUSIONS. Investigators may increase response rates by including more money in the initial questionnaire packet, but there may be diminishing returns to serial increments in incentives greater than $5. Including smaller incentives in more questionnaires may maximize total responses. C1 Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Michigan, Sch Med, Dept Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI 48109 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Asch, DA (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, 3644 Locust Walk, Philadelphia, PA 19104 USA. NR 18 TC 62 Z9 61 U1 0 U2 2 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 SEP PY 2002 VL 40 IS 9 BP 834 EP 839 DI 10.1097/01.MLR.0000024722.29926.3D PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 589ZD UT WOS:000177790900012 PM 12218773 ER PT J AU Bush, RK AF Bush, RK TI Asthma - Preface SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 William S Middleton Mem Vet Adm Med Ctr, Dept Allergy, Madison, WI 53705 USA. RP Bush, RK (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Allergy, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2002 VL 86 IS 5 BP XI EP XII AR PII S0025-7125(02)00027-5 DI 10.1016/S0025-7125(02)00027-5 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 612RF UT WOS:000179088700001 ER PT J AU Bush, RK AF Bush, RK TI Environmental controls in the management of allergic asthma SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID HOUSE-DUST-MITE; REDUCING RELATIVE-HUMIDITY; FEL-D-I; INDOOR ALLERGENS; MECHANICAL VENTILATION; CHILDHOOD ASTHMA; CAT ALLERGEN; DOUBLE-BLIND; MANCHESTER ASTHMA; RANDOMIZED TRIAL AB Sensitization to aeroallergens is a risk factor for the development of asthma in children and adults and ongoing exposure perpetuates the symptoms. Sensitivity to indoor allergens (house dust mites, pet dander, and cockroaches) and to the fungus Alternaria is most closely linked to these processes. Exposure avoidance and reduction have been shown significantly to improve asthma symptoms. Implementation of methods to achieve these results is an important part of asthma therapy. C1 William S Middleton Mem Vet Adm Med Ctr, Dept Allergy, Madison, WI 53705 USA. RP Bush, RK (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Allergy, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 78 TC 2 Z9 2 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2002 VL 86 IS 5 BP 973 EP + AR PII S0025-7125(02)00029-9 DI 10.1016/S0025-7125(02)00029-9 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 612RF UT WOS:000179088700005 PM 12428541 ER PT J AU Bush, RK AF Bush, RK TI The use of anti-IgE in the treatment of allergic asthma SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID HUMANIZED MONOCLONAL-ANTIBODY; SERUM IGE; AIRWAY RESPONSIVENESS; IMMUNE-RESPONSE; OMALIZUMAB; DISEASE; RHINITIS; THERAPY; COSTIMULATION; CHILDHOOD AB Allergic sensitization plays a significant role in the pathogenesis of asthma in many patients. Immunotherapy of allergic asthma is controversial. Large-scale trials in patients aged 6 to 76 years with moderate-to-severe allergic asthma have shown that anti-IgE (omalizumab) therapy is safe and effective in reducing corticosteroid dosages and preventing exacerbations. C1 William S Middleton Mem Vet Adm Med Ctr, Dept Allergy, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Sect Allergy & Immunol, Madison, WI 53792 USA. RP Bush, RK (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Allergy, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 41 TC 8 Z9 8 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2002 VL 86 IS 5 BP 1113 EP + AR PII S0025-7125(02)00036-6 DI 10.1016/S0025-7125(02)00036-6 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 612RF UT WOS:000179088700012 PM 12428547 ER PT J AU Bosch, JL Halpern, E Gazelle, GS AF Bosch, JL Halpern, E Gazelle, GS TI Comparison of preference-based utilities of the Short-Form 36 Health Survey and Health Utilities Index before and after treatment of patients with intermittent claudication SO MEDICAL DECISION MAKING LA English DT Article DE health status; utilities; quality of life; Short-Form 36 Health Survey; Health Utilities Index; intermittent claudication; peripheral vascular disease ID QUALITY-OF-LIFE; COST-EFFECTIVENESS; CLINICAL-TRIAL; EUROQOL EQ-5D; RECOMMENDATIONS; DISEASE; SF-36; HUI3 AB The authors compared SF-36 utilities with Health Utilities Index (HUI) utilities (HUI2 and HUI3) assessed in patients with intermittent claudication. A total of 87 patients with intermittent claudication completed the SF-36 and HUI before and 1, 3, and 12 months after revascularization. Utilities were estimated using SF-36 and HUI published algorithms (i.e., both algorithms were based on standard-gamble utilities assessed in random samples of the general population). The utilities were compared using repeated-measures multivariate analysis of variance, paired t tests, and univariate linear regression analyses. Before treatment, the mean SF-36 and HUI3 utilities were the some (0.66 vs. 0.66, P = 0.92) and less than the mean HUI2 utility (0.70, P = 0.02). After treatment, all utilities showed improvement from before treatment (P < 0.05); the gain in utilities from treatment was lowest when using the SF-36 (e.g., 0.74, 0.80, 0.77 at 3 months for the SF-36, HUI2, and HUI3, respectively). The correlations of changes over time of the SF-36 with HUI2 utilities and of the SF-36 with HUI3 utilities were 0.39 and 0.49, respectively. The relationships between the SF-36 and HUI2 or HUI3 utilities were moderate to good (i.e., range-adjusted R-2 = 31% to 72%). The results suggest that SF-36 data can be transformed to preference-based utilities and be used for economic evaluation in health care. The gain in utilities from treatment, however, was less for SF-36 utilities than for HUI utilities. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,DATA Grp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Rotterdam, Netherlands. RP Bosch, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,DATA Grp, Zero Emerson Pl,Suite 2H, Boston, MA 02114 USA. NR 17 TC 22 Z9 22 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2002 VL 22 IS 5 BP 403 EP 409 DI 10.1177/02729802236928 PG 7 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 595BT UT WOS:000178087500003 PM 12365482 ER PT J AU Newhauser, WD Burns, J Smith, AR AF Newhauser, WD Burns, J Smith, AR TI Dosimetry for ocular proton beam therapy at the Harvard Cyclotron Laboratory based on the ICRU Report 59 SO MEDICAL PHYSICS LA English DT Article DE ocular; proton; beam; dosimetry ID CHOROIDAL MELANOMA; FARADAY CUP; MACULAR DEGENERATION; RADIATION-THERAPY; UVEAL MELANOMA; IRRADIATION; RECOMMENDATIONS AB The Massachusetts General Hospital, the Harvard Cyclotron Laboratory (HCL), and the Massachusetts Eye and Ear Infirmary have treated almost 3000 patients with ocular disease using high-energy external-beam proton radiation therapy since 1975. The absorbed dose standard for ocular proton therapy beams at HCL was based on a fluence measurement with a Faraday cup (FC). A majority of proton therapy centers worldwide, however, use an absorbed dose standard that is based on an ionization chamber (IC) technique. The ion chamber calibration is deduced from a measurement in a reference Co-60 photon field together with a calculated correction factor that takes into account differences in a chamber's response in Co-60 and proton fields. In this work, we implemented an ionization chamber-based absolute dosimetry system for the HCL ocular beamline based on the recommendations given in Report 59 by the International Commission on Radiation Units and Measurements. Comparative measurements revealed that the FC system yields an absorbed dose to water value that is 1.1% higher than was obtained with the IC system. That difference is small compared with the experimental uncertainties and is clinically insignificant. In June of 1998, we adopted the IC-based method as our standard practice for the ocular beam. (C) 2002 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Cyclotron Lab, Cambridge, MA 02138 USA. RP Newhauser, WD (reprint author), Massachusetts Gen Hosp, 55 Fruit St,NPT-100, Boston, MA 02114 USA. NR 52 TC 21 Z9 21 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2002 VL 29 IS 9 BP 1953 EP 1961 DI 10.1118/1.1487425 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 595EC UT WOS:000178093000001 PM 12349914 ER PT J AU Deasy, JO Niemierko, A Herbert, D Yan, D Jackson, A Ten Haken, RK Langer, M Sapareto, S AF Deasy, JO Niemierko, A Herbert, D Yan, D Jackson, A Ten Haken, RK Langer, M Sapareto, S TI Methodological issues in radiation dose-volume outcome analyses: Summary of a joint AAPM/NIH workshop SO MEDICAL PHYSICS LA English DT Review DE outcomes analysis; TCP; NTCP; volume effects ID CELL LUNG-CANCER; EXTERNAL-BEAM IRRADIATION; PLANNING TARGET VOLUME; PROSTATE-CANCER; NORMAL TISSUE; 3-DIMENSIONAL TREATMENT; CONFORMAL RADIOTHERAPY; HEALTH-CARE; INTRAHEPATIC MALIGNANCIES; CONVENTIONAL RADIOTHERAPY AB This report represents a summary of presentations at a joint workshop of the National Institutes of Health and the American Association of Physicists in Medicine (AAPM). Current methodological issues in dose-volume modeling are addressed here from several different perspectives. Areas of emphasis include (a) basic modeling issues including the equivalent uniform dose framework and the bootstrap method, (b) issues in the valid use of statistics, including the need for meta-analysis, (c) issues in dealing with organ deformation and its effects on treatment response, (d) evidence for volume effects for rectal complications, (e) the use of volume effect data in liver and lung as a basis for dose escalation studies, and (f) implications of uncertainties in volume effect knowledge on optimized treatment planning. Taken together, these approaches to studying volume effects describe many implications for the development and use of this information in radiation oncology practice. Areas of significant interest for further research include the meta-analysis of clinical data; inter-institutional pooled data analyses of volume effects; analyses of the uncertainties in outcome prediction models, minimal parameter number outcome models for ranking treatment plans (e.g., equivalent uniform dose); incorporation of the effect of motion in the outcome prediction; dose-escalation/isorisk protocols based on outcome models; the use of functional imaging to study radio-response; and the need for further small animal tumor control probability/normal tissue complication probability studies. (C) 2002 American Association of Physicists in Medicine. C1 Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ S Alabama, Coll Med, Mobile, AL 36617 USA. William Beaumont Hosp, Royal Oak, MI 48073 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Indiana Univ, Indianapolis, IN 46202 USA. Good Samaritan Reg Med Ctr, Phoenix, AZ 85006 USA. RP Washington Univ, Sch Med, Dept Radiat Oncol, Box 8224,510 So Kingshighway Blvd, St Louis, MO 63110 USA. EM deasy@radonc.wustl.edu OI Deasy, Joseph/0000-0002-9437-266X FU NCI NIH HHS [CA21239, 2PO1-CA-59017, CA50628, CA59827, CA71785, CA85181] NR 122 TC 36 Z9 37 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD SEP PY 2002 VL 29 IS 9 BP 2109 EP 2127 DI 10.1118/1.1501473 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 595EC UT WOS:000178093000019 PM 12349932 ER PT J AU Simon, SR Volkan, K Hamann, C Duffey, C Fletcher, SW AF Simon, SR Volkan, K Hamann, C Duffey, C Fletcher, SW TI The relationship between second-year medical students' OSCE scores and USMLE Step 1 scores SO MEDICAL TEACHER LA English DT Article ID STRUCTURED CLINICAL EXAMINATION; COMPETENCE; COURSES AB The relationship between objective structured clinical examinations (OSCEs) and standardized tests is not well known. We linked second-year medical students' physical diagnosis OSCE scores from 1998, 1999 and 2000 (n=355) with demographic information, Medical College Admission Test (MCAT) scores, and United States Medical Licensing Examination (USMLE) Step 1 scores. The correlation coefficient for the total OSCE score with USMLE Step 1 score was 0.41 (p<0.001). Two of 7 skills areas-diagnosis and identification of abnormality-were significant multivariate correlates of USMLE Step 1 score. OSCE station scores accounted for approximately 22% of the variability in USMLE Step 1 scores. A second-year OSCE in physical diagnosis is correlated with scores on the USMLE Step 1 exam, with skills that foreshadow the clinical clerkships most predictive of USMLE scores. This correlation suggests predictive validity of this OSCE and supports the use of OSCEs early in medical school. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. Calif State Univ Channel Isl, Dept Educ, Camarillo, CA USA. Calif State Univ Channel Isl, Dept Psychol, Camarillo, CA USA. Harvard Univ, Sch Med, Off Registrar, Boston, MA 02215 USA. Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. RP Simon, SR (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. NR 13 TC 25 Z9 25 U1 0 U2 1 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PD SEP PY 2002 VL 24 IS 5 BP 535 EP 539 DI 10.1080/0142159021000012586 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 611YD UT WOS:000179044800014 PM 12450476 ER PT J AU Castiglioni, B Sutton, DA Rinaldi, MG Fung, J Kusne, S AF Castiglioni, B Sutton, DA Rinaldi, MG Fung, J Kusne, S TI Pseudallescheria boydii (anamorph Scedosporium apiospermum) infection in solid organ transplant recipients in a tertiary medical center and review of the literature SO MEDICINE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; BONE-MARROW TRANSPLANTATION; IN-VITRO ACTIVITY; AMPHOTERICIN-B; BRAIN-ABSCESS; ALLESCHERIA-BOYDII; PULMONARY PSEUDALLESCHERIASIS; CLINICAL-SIGNIFICANCE; PETRIELLIDIUM-BOYDII; ASPERGILLUS-TERREUS AB Scedosporium apiospermum (Sca) is a ubiquitous filamentous fungus capable of causing invasive disease. We reviewed our electronic microbiology records and the English-language literature. Between 1976 and December 1999 we identified 23 solid organ transplant recipients with Sca infection, 7 of which occurred between December 1987 and December 1999 at our institution. Overall incidence was 1 per 1,000 patients, with a trend of higher incidence in patients receiving lung transplants compared with other transplant organs (p = 0.06). The 23 patients included liver (4), kidney (8), heart (8), lung (2), and heart/lung (1) recipients. Male to female ratio was 19:4, and the mean age was 46 +/- 12 (SD) years. Fungal infection was diagnosed at a median of 4 months (range, 0.4-156 mo) after transplant. The clinical presentation included disseminated disease (8), skin lesions (3), lung disease (5), endophthalmitis (1), meningitis (1), brain abscess with or without extension to eye (3), fungal mycotic aneurysm (1), and sinusitis (1). Seven (30%) patients had intravascular infection, and 11 (48%) patients had central nervous system involvement. Antifungal therapy was accompanied by surgical debridement in 9 cases. Three additional patients were found to have an-way colonization only and received itraconazole prophylaxis, without evidence of disease. Of 22 patients with known outcome, 16 (72.7%) died. Five of 6 patients who survived had localized infections: skin lesions (n = 3), sinus fungus ball (n = 1), and solitary lung nodule (n = 1). All patients with disseminated disease and 10 of 11 patients with central nervous system disease died. An exception was I patient with a brain abscess, successfully treated with voriconazole and surgical drainage. Sca infection is rare but. is associated with high mortality. Early diagnosis by,culture is important because Sca is resistant to amphotericin B, routinely used in the empiric therapy of invasive fungal infections. Treatment with the combination of an antifungal and surgery may have a better outcome. Voriconazole promises to be an effective antifungal agent. Cultures positive for Sca should not be ignored, and long-term antifungal prophylaxis in candidates, and transplant recipients should he considered. C1 Univ Pittsburgh, Ctr Med, Thomas E Starzl Transplantat Inst, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Med, Thomas E Starzl Transplantat Inst, Dept Surg, Pittsburgh, PA USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Kusne, S (reprint author), Univ Pittsburgh, Ctr Med, Div Infect Dis, Falk Med Bldg,Suite 3A,3601 5th Ave, Pittsburgh, PA 15213 USA. NR 70 TC 105 Z9 108 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD SEP PY 2002 VL 81 IS 5 BP 333 EP 348 DI 10.1097/01.md.0000030341.26556.e8 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 595WH UT WOS:000178131200001 PM 12352630 ER PT J AU Matsuda, M DeFronzo, RA Glass, L Consoli, A Giordano, M Bressler, P DelPrato, S AF Matsuda, M DeFronzo, RA Glass, L Consoli, A Giordano, M Bressler, P DelPrato, S TI Glucagon dose-response curve for hepatic glucose production and glucose disposal in type 2 diabetic patients and normal individuals SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID POSTPRANDIAL HYPERGLYCEMIA; INSULIN; METABOLISM; MELLITUS; HYPERGLUCAGONEMIA; SUPPRESSION; HUMANS; NIDDM; GLUCONEOGENESIS; HORMONE AB This study sought to examine whether enhanced hepatic sensitivity to glucagon contributes to impaired glucose homeostasis in subjects with type 2 diabetes mellitus (T2DM). Eight T2DM and 9 age-, weight-, and gender-matched nondiabetic subjects received a 4-hour glucagon infusion at the rates of 0.2, 0.5, 2, 6, and 8 ng . kg(-1) . min(-1) while maintaining the plasma insulin concentration constant at the basal level with exogenous infusions of somatostatin and insulin, On the evening prior to study, diabetic subjects received a low-dose insulin infusion at a rate designed to maintain euglycemia and this infusion rate was continued until the end of the glucagon infusion study on the following day. Each glucagon infusion study was performed on a separate day and in random order. 3-H-3-glucose was infused in all studies to measure endogenous glucose production (EGP) and the rate of whole body glucose disposal. During the first 2 hours (0 to 120 minutes) of glucagon infusion, EGP increased sharply in both groups, and the initial rate of rise in EGP was higher in control versus diabetic subjects. During the last 2 hours (120 to 240 minutes) of glucagon infusion, EGP in the diabetics tended to be higher than controls during the 3 lower glucagon infusion rates and this difference reached statistical significance (P<.05 to .01) during the 6 and 8 ng . kg(-1 .) min(-1) infusions. During the 2 hours following cessation of glucagon (240- to 360-minute time period), the stimulation of glucose disappearance from plasma was impaired (P<.05) during all 5 glucagon infusion rates in the diabetics compared to controls. We conclude that in T2DM patients, the initial (0 to 120 minutes) stimulation of hepatic glucose output (which primarily reflects glycogenolysis) by glucagon is not enhanced in T2DM patients. The late (120 to 240 minutes) stimulation of hepatic glucose output (which primarily reflects gluconeogenesis) by glucagon tends to be increased, especially at supraphysiologic plasma glucagon concentrations, Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Diabet Div, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. RP Univ Texas, Hlth Sci Ctr, Dept Med, Diabet Div, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. OI Matsuda, Masafumi/0000-0001-8543-1616 FU NCRR NIH HHS [RR01346]; NIDDK NIH HHS [DK24092] NR 47 TC 39 Z9 40 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2002 VL 51 IS 9 BP 1111 EP 1119 DI 10.1053/meta.2002.34700 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592HA UT WOS:000177930000006 PM 12200754 ER PT J AU Hadigan, C Borgonha, S Rabe, J Young, V Grinspoon, S AF Hadigan, C Borgonha, S Rabe, J Young, V Grinspoon, S TI Increased rates of lipolysis among human immunodeficiency virus-infected men receiving highly active antiretroviral therapy SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID INSULIN-RESISTANCE; LIPODYSTROPHY AB Human immunodeficiency virus (HIV) lipodystrophy is associated with fat redistribution, dyslipidemia, and insulin resistance; however, the mechanism of insulin resistance remains unknown, We hypothesized that HIV-infected subjects with fat redistribution have increased rates of lipolysis and increased circulating free fatty acid (FFA) levels that contribute to insulin resistance. Anthrompometric and body composition data were obtained and a standard 75-g oral glucose tolerance test (OGTT) was performed on day 1 of the study. Stable isotope infusions of glycerol and palmitate were completed following an overnight fast to assess rates of lipolysis and FFA flux in HIV-Infected men (n = 19) with and without fat redistribution and healthy controls (n = 8) on day 2. Total FFA levels after standard glucose challenge were increased among HIV-infected subjects and positively associated with abdominal visceral adipose tissue area. In contrast, fasting total FFA levels were inversely associated with subcutaneous fat area. Rates of basal lipolysis were significantly increased among HIV-infected subjects (rate of appearance [Ra] glycerol, 4.1 +/- 0.2 v 3.3 +/- 0.2 mumol/kg/min in controls; P = .02). Among HIV-infected subjects, use of stavudine (P = .006) and the rate of lipolysis (ie, Ra glycerol, P = .02) were strong positive predictors of insulin resistance as measured by insulin response to glucose challenge, controlling for effects of age, body mass index (BMI), waist-to-hip ratio (WHR), and protease inhibitor (PI) exposure. These data demonstrate increased rates of lipolysis and increased total FFA levels in HIV-infected subjects and suggest that increased lipolysis may contribute to insulin resistance in this patient population. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. RP Hadigan, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR300088]; NIDDK NIH HHS [K23-DK02844, R01-DK59535] NR 16 TC 108 Z9 109 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2002 VL 51 IS 9 BP 1143 EP 1147 DI 10.1053/meta.2002.34704 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592HA UT WOS:000177930000010 PM 12200758 ER PT J AU Murray, SS Tu, KN Young, KL Murray, EJB AF Murray, SS Tu, KN Young, KL Murray, EJB TI The effects of Lovastatin on proteasome activities in highly purified rabbit 20 S proteasome preparations and mouse MC3T3-E1 osteoblastic cells SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID COA REDUCTASE INHIBITORS; IN-VITRO; DIFFERENTIATION; PROLIFERATION; SIMVASTATIN; COMPACTIN; RISK; OSTEOCLASTS; ACTIVATION; UBIQUITIN AB A number of clinical studies suggest that the use of the lipid-lowering agents collectively referred to as statins (hydroxymethyl glutaryl coenzyme A [HMG-CoA] reductase inhibitors) is associated with increased bone density, reduced fracture risk, and net bone anabolism. Statins ( less than or equal to5 mumol/L) stimulate rodent bone formation, but the mechanistic basis remains unclear. Since statins and the proteasome inhibitor lactacystin are structurally similar, and high doses (greater than or equal to40 mumol/L) of statins can inhibit the chymotryptic activity of the proteasome, it has been hypothesized that statins exert their anabolic effects on bone, in part, by inhibiting the proteasome, the major eukaryotic intracellular regulatory protease. This hypothesis conflicts with reports that statins stimulate proteasome activity and that proteasome-catalyzed degradation of specific substrates is required for cell proliferation, differentiation, and survival. Our chief objective was to determine the effects of statins (less than or equal to10 mumol/L) on the chymotryptic activity of the proteasome in the 20 S proteasome and intact murine MC3T3-E1 cells cultured to low density (preosteoblasts) or high density (differentiated osteoblasts). Lovastatin (0.001 mumol/L to 5.0 mumol/L) stimulated the chymotryptic activity of the highly purified 20 S proteasome. Preosteoblasts and differentiated osteoblasts treated with 1, 5, or 10 mumol/L lovastatin for 1 hour exhibited morphologic abnormalities that were ameliorated by preincubation and treatment with 20 mumol/L mevalonate. The chymotryptic activity of the preosteoblast proteasome increased after 2 days of 1.0 mumol/L or 5.0 mumol/L lovastatin treatment. In addition, the DNA and protein contents of 1.0 mumol/L or 5.0 mumol/L lovastatin-treated preosteoblast cultures were lower those that observed in vehicle-, 0.01 mumol/L lovastatin-, or 0.10 mumol/L lovastatin-treated cultures, The chymotryptic activity of the proteasome was much lower in differentiated osteoblasts than in preosteoblasts. Two days of treatment with 1 mumol/L lovastatin modestly stimulated the chymotryptic activity of the proteasome in differentiated osteoblasts, but had no effects on total protein or DNA, compared to cultures treated with vehicle or lower doses of lovastatin. Thus, the data support the hypothesis that statins stimulate proteasome activities in highly purified proteasome preparations and preosteoblastic cells. Treating preosteoblastic or differentiated MC3T3-E1 cells with lovastatin concentrations greater than or equal to 1 mumol/L resulted in abnormal morphology and reduced the DNA and protein levels in preosteoblastic cultures, confirming the adverse effects of statins previously reported for other cells. In conclusion, the hypothesis that lovastatin exerts its anabolic effects on bone by inhibiting the proteasome activity of the osteoblast was refuted, and the effects of lovastatin on MC3T3-E1 cells were found to be highly dose- and development-dependent. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 VA Greater Los angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Serv Pharm, Sepulveda, CA 91343 USA. VA Greater Los angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Murray, SS (reprint author), VA Greater Los angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Serv Pharm, Mail Code 11-E,16111 Plummer St, Sepulveda, CA 91343 USA. NR 35 TC 13 Z9 13 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2002 VL 51 IS 9 BP 1153 EP 1160 DI 10.1053/meta.2002.34706 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592HA UT WOS:000177930000012 PM 12200760 ER PT J AU Villa, VM Harada, ND Washington, D Damron-Rodriguez, J AF Villa, VM Harada, ND Washington, D Damron-Rodriguez, J TI Health and functioning among four war eras of US veterans: Examining the impact of war cohort membership, socioeconomic status, mental health, and disease prevalence SO MILITARY MEDICINE LA English DT Article ID QUALITY-OF-LIFE; MILITARY SERVICE; VIETNAM EXPERIENCE; CONSEQUENCES; STRESSORS AB This analysis examines the self-rated health and functioning of World War II, Vietnam era, Korean Conflict, and Persian Gulf War veterans participating in the Veteran Identity Program Survey 2001. The results indicate that although World War II veterans are more likely to report poor health status and functioning, Vietnam-era veterans report more difficulty with specific activities of daily living and instrumental activities of daily living than any other era of veterans. These relationships remain when controlling for race/ethnicity, socioeconomic status, disease prevalence, and mental health status. These findings suggest that there are characteristics unique to the Vietnam experience that negatively affect this cohort of veterans. We suggest that further analysis examine the specific pathways through which the experience of being a Vietnam veteran affects health. In the meantime, health and social service planning within the Department of Veterans Affairs should explore the services that should be developed and targeted to this cohort of veterans so that they may remain independent in the community. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Policy & Social Res, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA USA. Calif State Polytech Univ Pomona, Pomona, CA 91768 USA. RP Villa, VM (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 25 TC 12 Z9 12 U1 0 U2 2 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD SEP PY 2002 VL 167 IS 9 BP 783 EP 789 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 653EA UT WOS:000181421200018 PM 12363172 ER PT J AU Levine, SS Weiss, A Erdjument-Bromage, H Shao, ZH Tempst, P Kingston, RE AF Levine, SS Weiss, A Erdjument-Bromage, H Shao, ZH Tempst, P Kingston, RE TI The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN-REMODELING COMPLEX; MYC TRANSGENIC MICE; GROUP PROTEINS; TRANSCRIPTIONAL REPRESSION; BMI-1 PROTOONCOGENE; GENE-EXPRESSION; SWI/SNF COMPLEX; HOMEOTIC GENE; ZINC FINGER; SEX COMB AB The Polycomb group (PcG) genes are required to maintain homeotic genes in a silenced state during development in drosophila and mammals and are thought to form several distinct silencing complexes that maintain homeotic gene repression during development. Mutations in the PcG genes result in developmental defects and have been implicated in human cancer. Although some PcG protein domains are conserved between flies and humans, substantial regions of several PcG proteins are divergent and humans contain multiple versions of each PcG gene. To determine the effects of these changes on the composition and function of a PcG complex, we have purified a human Polycomb repressive complex from HeLa cells (hPRC-H) that contains homologues of PcG proteins found in drosophila embryonic PRC1 (dPRC1). hPRC-H was found to have fewer components than dPRC1, retaining the PcG core proteins of dPRC1 but lacking most non-PcG proteins. Preparations of hPRC-H contained either two or three different homologues of most of the core PcG proteins, including a new Ph homologue we have named HPH3. Despite differences in composition, dPRC1 and hPRC-H have similar functions: hPRC-H is able to efficiently block remodeling of nucleosomal arrays through a mechanism that does not block the ability of nucleases to access and cleave the arrays. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. OI Tempst, Paul/0000-0002-6680-3987 NR 66 TC 235 Z9 255 U1 1 U2 11 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 SEP PY 2002 VL 22 IS 17 BP 6070 EP 6078 DI 10.1128/MCB.22.17.6070-6078.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 584UZ UT WOS:000177488300005 PM 12167701 ER PT J AU Yarm, FR AF Yarm, FR TI Plk phosphorylation regulates the microtubule-stabilizing protein TCTP SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POLO-LIKE KINASE; EHRLICH ASCITES TUMOR; XENOPUS EGG EXTRACTS; ANAPHASE-PROMOTING COMPLEX; CELL-CYCLE PROGRESSION; KINESIN-LIKE PROTEIN; SACCHAROMYCES-CEREVISIAE; SERINE/THREONINE KINASE; DROSOPHILA-POLO; MESSENGER-RNA AB The mitotic polo-like kinases have been implicated in the formation and function of bipolar spindles on the basis of their respective localizations and mutant phenotypes. To date, this putative regulation has been limited to a kinesin-like motor protein, a centrosomal structural protein, and two microtubule-associated proteins (MALPs). In this study, another spindle-regulating protein, the mammalian non-MAP microtubule-binding and -stabilizing protein, the translationally controlled tumor protein (TCTP), was identified as a putative Plk-interacting clone by a two-hybrid screen. Plk phosphorylates TCTP on two serine residues in vitro and cofractionates with the majority of kinase activity toward TCTP in mitotic cell lysates. In addition, these sites were demonstrated to be phosphorylated in vivo. Overexpression of a Plk phosphorylation site-deficient mutant of TCTP induced a dramatic increase in the number of multinucleate cells, rounded cells with condensed ball-like nuclei, and cells undergoing cell death, similar to both the reported anti-Plk antibody microinjection and the low-concentration taxol treatment phenotypes. These results suggest that phosphorylation decreases the microtubule-stabilizing activity of TCTP and promotes the increase in microtubule dynamics that occurs after metaphase. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Yarm, FR (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Room 620 Mayer, Boston, MA 02115 USA. FU NCI NIH HHS [CA62580]; NIGMS NIH HHS [GM59172, R01 GM059172] NR 73 TC 167 Z9 181 U1 0 U2 12 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 SEP PY 2002 VL 22 IS 17 BP 6209 EP 6221 DI 10.1128/MCB.22.17.6209-6221.2002 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 584UZ UT WOS:000177488300018 PM 12167714 ER PT J AU Yang, XF Ye, QR Press, B Han, RZ Bassing, CH Sleckman, BP Alt, FW Cantor, H AF Yang, XF Ye, QR Press, B Han, RZ Bassing, CH Sleckman, BP Alt, FW Cantor, H TI Analysis of the complex genomic structure of Bcl-x and its relationship to Bcl-x gamma expression after CD28-dependent costimulation SO MOLECULAR IMMUNOLOGY LA English DT Article DE Bcl-x gamma; apoptosis; TCR; alternative splicing; 3 ' untranslated region ID T-LYMPHOCYTES; CELL-SURVIVAL; APOPTOSIS; ANTIGEN; GENE AB The Bcl-xgamma cytosolic protein is essential for costimulatory activity after CD3/CD28 coligation. Here we delineate the Bcl-xgamma/Bcl-x genomic organization and the molecular mechanism that allows expression. We show that exon 4 of the Bcl-x gene encodes the unique C-terminal end of the Bcl-xgamma molecule while exons 5, 6, 7 and 8 are differentially transcribed to yield three alternative Bcl-xgamma 3' untranslated regions (UTR). CD28-dependent signals may increase levels of Bcl-xgamma protein through induction of an alternatively-spliced Bcl-xgamma 3' UTR that contains stem loop structures that stabilize Bcl-xgamma RNA. The ability receptor-induced signals to regulate the splicing pattern of the complex Bcl-x gene may allow T-cells to respond appropriately to antigenic stimuli. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Cantor, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Smith 722,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI48125/37833, AI 35714, AI20047, T32 AI07386]; PHS HHS [A13600, A112184] NR 22 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD SEP PY 2002 VL 39 IS 1-2 BP 45 EP 55 AR PII S0161-5890(02)00049-4 DI 10.1016/S0161-5890(02)00049-4 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 602WX UT WOS:000178528400007 PM 12213327 ER PT J AU Koelsch, S AF Koelsch, S TI The biological foundations of music. SO MUSIC PERCEPTION LA English DT Book Review C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02215 USA. RP Koelsch, S (reprint author), Harvard Univ, Sch Med, BIDMC, Dana 779,330 Brookline Ave, Boston, MA 02215 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU UNIV CALIF PRESS PI BERKELEY PA C/O JOURNALS DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 0730-7829 J9 MUSIC PERCEPT JI Music Percept. PD FAL PY 2002 VL 20 IS 1 BP 87 EP 91 PG 5 WC Music; Psychology, Experimental SC Music; Psychology GA 594UR UT WOS:000178069900005 ER PT J AU Kaur, M Zhang, YZ Liu, WH Tetradis, S Price, BD Makrigiorgos, GM AF Kaur, M Zhang, YZ Liu, WH Tetradis, S Price, BD Makrigiorgos, GM TI Ligation of a primer at a mutation: a method to detect low level mutations in DNA SO MUTAGENESIS LA English DT Article ID GENOTYPIC SELECTION METHODS; PCR-RFLP ASSAY; POINT MUTATIONS; NUCLEOTIDE ANALOGS; P53 MUTATIONS; RAS GENES; RESTRICTION; DIAGNOSIS; CANCER; TRANSFORMATION AB Detection of low frequency mutations following exposure to mutagens or during the early stages of cancer development is instrumental for risk assessment and molecular diagnosis. We present a sensitive new method to detect trace levels of DNA mutations induced within a large excess of wild-type sequences. The method is based on mutation-induced generation of new restriction enzyme recognition sites. A DNA sequence is amplified from genomic DNA or cDNA using a high fidelity polymerase. The purified PCR product is digested with a restriction enzyme that recognizes the newly generated restriction site, partially dephosphorylated and ligated with an oligonucleotide at the position of the mutation. The ligated oligonucleotide is then utilized in two rounds of PCR to amplify the mutated DNA but not the wild-type allele that contains no restriction site. An A-->T polymorphism in mRNA (tenascin gene, A(2366)-->T, Asn-->Ile) and a G-->A polymorphism in genomic DNA (Ku gene, G(74582)-->A, Val-->Ile), both of which generate a restriction site for the enzyme SAU3A1, demonstrate the application. Eleven patient samples pre-characterized for the G(74582)-->A polymorphism in the repair gene Ku are used to demonstrate the reliability of this approach. This technique quantitatively detects the Ku G-->A polymorphism at a mutant frequency of 1.6x10(-6) relative to the wild-type allele. Mutations in p53 that are frequently induced by mutagens can readily be detected using the present method. As an example, using a second enzyme BbvI, a mutation frequently encountered in human cancers (G(14154)-->A mutation, p53 codon 245, Arg-->Gln) was detected in patient samples. The process does not require radioactivity, utilizes established procedures and overcomes several factors known to produce false positives in RFLP-based assays. The present amplification via primer ligation at the mutation (APRIL-ATM) has potential applications in the detection of mutagen-generated genetic alterations, early detection of tumor marker mutations in bodily discharges and the diagnosis of minimal residual disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Makrigiorgos, GM (reprint author), Brigham Dana Farber Childrens Hosp, Longwood Radiat Oncol Ctr, Level L2,75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [CA/HG 90422, CA 83234] NR 33 TC 15 Z9 15 U1 4 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 2002 VL 17 IS 5 BP 365 EP 373 DI 10.1093/mutage/17.5.365 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 589LH UT WOS:000177759500002 PM 12202623 ER PT J AU Makrigiorgos, GM Chakrabarti, S Zhang, YZ Kaur, M Price, BD AF Makrigiorgos, GM Chakrabarti, S Zhang, YZ Kaur, M Price, BD TI A PCR-based amplification method retaining the quantitative difference between two complex genomes SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION; MESSENGER-RNA; BREAST-CANCER; CDNA; HYBRIDIZATION; DISPLAY AB With the increasing emergence of genome-wide analysis technologies (including comparative genomic hybridization (CGH)(1), expression profiling on microarrays(2), differential display (DD)(3), subtractive hybridization, and representational difference analysis (RDA)(4,5)), there is frequently a need to amplify entire genomes or cDNAs by PCR to obtain enough material for comparisons among target and control samples. A major problem with PCR is that amplification occurs in a nonlinear manner and reproducibility is influenced by stray impurities(6). As a result, when two complex DNA populations are amplified separately, the quantitative relationship between two genes after amplification is generally not the same as their relation before amplification(7). Here we describe balanced PCR, a procedure that faithfully retains the difference among corresponding amplified genes by using a simple principle. Two distinct genomic DNA samples are tagged with oligonucleotides containing both a common and a unique DNA sequence. The genomic DNA samples are pooled and amplified in a single PCR tube using the common DNA tag. By mixing the two genomes, PCR loses the ability to discriminate among the different alleles and the influence of impurities is eliminated. The PCR-amplified pooled samples can be separated using the DNA tag unique to each individual genomic DNA sample. The principle of this method has been validated with synthetic DNA, genomic DNA, and cDNA applied on microarrays. By removing the bias of PCR, this method allows a balanced amplification of allelic fragments from two complex DNAs even after three sequential rounds of PCR. This balanced PCR approach should allow genetic analysis in minute laser-microdissected tissues, paraffin-embedded archived material, or single cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. NR 18 TC 57 Z9 62 U1 2 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2002 VL 20 IS 9 BP 936 EP 939 DI 10.1038/nbt724 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 589KN UT WOS:000177757700028 PM 12161758 ER PT J AU Look, AT AF Look, AT TI A leukemogenic twist for GATA1 SO NATURE GENETICS LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; THROMBOCYTOPENIA; MUTATION C1 Harvard Univ, Sch Med, Dept Pediat, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dept Pediat, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 15 TC 12 Z9 14 U1 0 U2 0 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 SEP PY 2002 VL 32 IS 1 BP 83 EP 84 DI 10.1038/ng960 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 588RR UT WOS:000177714900002 PM 12172549 ER PT J AU Reich, DE Schaffner, SF Daly, MJ McVean, G Mullikin, JC Higgins, JM Richter, DJ Lander, ES Altshuler, D AF Reich, DE Schaffner, SF Daly, MJ McVean, G Mullikin, JC Higgins, JM Richter, DJ Lander, ES Altshuler, D TI Human genome sequence variation and the influence of gene history, mutation and recombination SO NATURE GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; NEUTRAL ALLELE MODEL; LINKAGE DISEQUILIBRIUM; INTRAGENIC RECOMBINATION; POPULATION EXPANSION; FINITE POPULATION; CANDIDATE GENES; SNP MAP; DIVERSITY; REGIONS AB Variation in the human genome sequence is key to understanding susceptibility to disease in modern populations and the history of ancestral populations. Unlocking this information requires knowledge of the patterns and underlying causes of human sequence diversity. By applying a new population-genetic framework to two genome-wide polymorphism surveys, we find that the human genome contains sizeable regions (stretching over tens of thousands of base pairs) that have intrinsically high and low rates of sequence variation. We show that the primary determinant of these patterns is shared genealogical history. Only a fraction of the variation (at most 25%) is due to the local mutation rate. By measuring the average distance over which genealogical histories are typically preserved, these data provide the first genome-wide estimate of the average extent of correlation among variants (linkage disequilibrium). The results are best explained by extreme variability in the recombination rate at a fine scale, and provide the first empirical evidence that such recombination 'hot spots' are a general feature of the human genome and have a principal role in shaping genetic variation in the human population. C1 MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA 02139 USA. Univ Oxford, Dept Stat, Oxford OX1 3TG, England. Wellcome Trust Sanger Inst, Cambridge, England. MIT, Dept Biol, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Altshuler, D (reprint author), MIT, Ctr Genome Res, Whitehead Inst, 1 Kendall Sq, Cambridge, MA 02139 USA. EM altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011 OI Altshuler, David/0000-0002-7250-4107; NR 46 TC 195 Z9 216 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2002 VL 32 IS 1 BP 135 EP 142 DI 10.1038/ng947 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 588RR UT WOS:000177714900012 PM 12161752 ER PT J AU Lund, AH Turner, G Trubetskoy, A Verhoeven, E Wientjens, E Hulsman, D Russell, R DePinho, RA Lenz, J van Lohuizen, M AF Lund, AH Turner, G Trubetskoy, A Verhoeven, E Wientjens, E Hulsman, D Russell, R DePinho, RA Lenz, J van Lohuizen, M TI Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient mice SO NATURE GENETICS LA English DT Article ID P53-DEPENDENT APOPTOSIS; P16(INK4A) EXPRESSION; CELL-PROLIFERATION; TUMOR SUPPRESSION; INK4A LOCUS; SENESCENCE; PROTEIN; P53; RAS; TRANSFORMATION AB We have used large-scale insertional mutagenesis to identify functional landmarks relevant to cancer in the recently completed mouse genome sequence. We infected Cdkn2a(-/-) mice with Moloney murine leukemia virus (MoMuLV) to screen for loci that can participate in tumorigenesis in collaboration with loss of the Cdkn2a-encoded tumor suppressors p16INK4a and p19ARF. Insertional mutagenesis by the latent retrovirus was synergistic with loss of Cdkn2a expression, as indicated by a marked acceleration in the development of both myeloid and lymphoid tumors. We isolated 747 unique sequences flanking retroviral integration sites and mapped them against the mouse genome sequence databases from Celera and Ensembl. In addition to 17 insertions targeting gene loci known to be cancer-related, we identified a total of 37 new common insertion sites (CISs), of which 8 encode components of signaling pathways that are involved in cancer. The effectiveness of large-scale insertional mutagenesis in a sensitized genetic background is demonstrated by the preference for activation of MAP kinase signaling, collaborating with Cdkn2a loss in generating the lymphoid and myeloid tumors. Collectively, our results show that large-scale retroviral insertional mutagenesis in genetically predisposed mice is useful both as a system for identifying genes underlying cancer and as a genetic framework for the assignment of such genes to specific oncogenic pathways. C1 Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol Genet & Med, Boston, MA 02115 USA. RP Lenz, J (reprint author), Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. RI Lund, Anders/F-4786-2014; OI Lund, Anders/0000-0002-7407-3398 NR 29 TC 174 Z9 178 U1 0 U2 2 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 SEP PY 2002 VL 32 IS 1 BP 160 EP 165 DI 10.1038/ng956 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 588RR UT WOS:000177714900016 PM 12185367 ER PT J AU Lee, JT AF Lee, JT TI Homozygous Tsix mutant mice reveal a sex-ratio distortion and revert to random X-inactivation SO NATURE GENETICS LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; CHROMOSOME INACTIVATION; XIST GENE; MOUSE; METHYLATION; CTCF; EXPRESSION; TRANSCRIPTION; ANTISENSE; MUTATION AB Tsix(1) controls X-chromosome inactivation (XCI) by blocking the accumulation of Xist(2-4) RNA on the future active X chromosome(5-7). Deleting Tsix on one X chromosome ((XX)-X-Delta) skews XCI toward the mutated X chromosome in the female soma. Here 1 have generated homozygous Tsix-null mice ((XXDelta)-X-Delta) to test how deleting the second allele affects the choice of XCI. Homozygosity leads to extremely low fertility and reveals two previously unknown non-mendelian patterns of inheritance. First, the sex ratio is skewed against female births so that one daughter is born for every two to three sons: Second, the pattern of XCI unexpectedly returns to random in surviving (XXDelta)-X-Delta mice. Thus, with respect to choice, mutation of Tsix yields a phenotypic abnormality in heterozygotes but not homozygotes. To reconcile the paradox of female loss with apparent reversion to random choice, I propose that deleting both Tsix alleles results In chaotic choice and that randomness in (XXDelta)-X-Delta survivors reflects a fortuitous selection of distinct X chromosomes as active and inactive. C1 Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 30 TC 56 Z9 58 U1 0 U2 1 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 SEP PY 2002 VL 32 IS 1 BP 195 EP 200 DI 10.1038/ng939 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 588RR UT WOS:000177714900022 PM 12145659 ER PT J AU Maser, RS DePinho, RA AF Maser, RS DePinho, RA TI Keeping telomerase in its place SO NATURE MEDICINE LA English DT Editorial Material ID CATALYTIC SUBUNIT; HTERT; VARIANT C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Maser, RS (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Maser, Richard/B-2970-2012 NR 12 TC 20 Z9 20 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2002 VL 8 IS 9 BP 934 EP 936 DI 10.1038/nm0902-934 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 589KQ UT WOS:000177757900019 PM 12205452 ER PT J AU Weijzen, S Rizzo, P Braid, M Vaishnav, R Jonkheer, SM Zlobin, A Osborne, BA Gottipati, S Aster, JC Hahn, WC Rudolf, M Siziopikou, K Kast, WM Miele, L AF Weijzen, S Rizzo, P Braid, M Vaishnav, R Jonkheer, SM Zlobin, A Osborne, BA Gottipati, S Aster, JC Hahn, WC Rudolf, M Siziopikou, K Kast, WM Miele, L TI Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells SO NATURE MEDICINE LA English DT Article ID INTRACELLULAR DOMAIN; NUCLEAR ACCESS; EXPRESSION; DROSOPHILA; PATHWAY; DIFFERENTIATION; TRANSCRIPTION; INDUCTION; ALLELES; GENE AB Truncated Notch receptors have transforming activity in vitro and in vivo. However, the role of wild-type Notch signaling in neoplastic transformation remains unclear. Ras signaling is deregulated in a large fraction of human malignancies and is a major target for the development of novel cancer treatments. We show that oncogenic Ras activates Notch signaling and that wildtype Notch-1 is necessary to maintain the neoplastic phenotype in Ras-transformed human cells in vitro and in vivo. Oncogenic Ras increases levels and activity of the intracellular form of wildtype Notch-1, and upregulates Notch ligand Delta-1 and also presenilin-1, a protein involved in Notch processing, through a p38-mediated pathway. These observations place Notch signaling among key downstream effectors of oncogenic Ras and suggest that it might be a novel therapeutic target. C1 Univ Illinois, Dept Biopharmaceut Sci & Canc Ctr, Chicago, IL 60607 USA. Loyola Univ, Canc Immunol Program, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Loyola Univ, Dept Pathol, Maywood, IL 60153 USA. RP Miele, L (reprint author), Univ Illinois, Dept Biopharmaceut Sci & Canc Ctr, Chicago, IL 60607 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [R01 CA 84065/01, R01 CA/AI 78399]; PHS HHS [R01 A47922] NR 45 TC 375 Z9 399 U1 2 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2002 VL 8 IS 9 BP 979 EP 986 DI 10.1038/nm754 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 589KQ UT WOS:000177757900033 PM 12185362 ER PT J AU Akbari, O Freeman, GJ Meyer, EH Greenfield, EA Chang, TT Sharpe, AH Berry, G DeKruyff, RH Umetsu, DT AF Akbari, O Freeman, GJ Meyer, EH Greenfield, EA Chang, TT Sharpe, AH Berry, G DeKruyff, RH Umetsu, DT TI Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity SO NATURE MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; HEAT-KILLED LISTERIA; MOUSE BONE-MARROW; DENDRITIC CELLS; IN-VIVO; IMMUNE-RESPONSES; CO-STIMULATION; MOLECULE ICOS; INFLAMMATION; EXPRESSION AB Asthma is caused by T-helper cell 2 (Th2)-driven immune responses, but the immunological mechanisms that protect against asthma development are poorly understood. T-cell tolerance, induced by respiratory exposure to allergen, can inhibit the development of airway hyperreactivity (AHR), a cardinal feature of asthma, and we show here that regulatory T (T-R) cells can mediate this protective effect. Mature pulmonary dendritic cells in the bronchial lymph nodes of mice exposed to respiratory allergen induced the development of TR cells, in a process that required T-cell costimulation via the inducible costimulator (ICOS)-ICOS-ligand pathway. The TR cells produced IL-10, and had potent inhibitory activity; when adoptively transferred into sensitized mice, TR cells blocked the development of AHR. Both the development and the inhibitory function of regulatory cells were dependent on the presence of IL-10 and on ICOS-ICOS-ligand interactions. These studies demonstrate that TR cells and the ICOS-ICOS-ligand signaling pathway are critically involved in respiratory tolerance and in downregulating pulmonary inflammation in asthma. C1 Stanford Univ, Dept Pediat, Sch Med, Div Immunol & Allergy, Stanford, CA 94305 USA. Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Immunol Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Umetsu, DT (reprint author), Stanford Univ, Dept Pediat, Sch Med, Div Immunol & Allergy, Stanford, CA 94305 USA. FU NCI NIH HHS [CA84500]; NHLBI NIH HHS [R01HL62348]; NIAID NIH HHS [AI24571, AI39671, AI26322, T32 AI007290, AI38310] NR 59 TC 545 Z9 577 U1 2 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2002 VL 8 IS 9 BP 1024 EP 1032 DI 10.1038/nm745 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 589KQ UT WOS:000177757900039 PM 12145647 ER PT J AU Kaelin, WG AF Kaelin, WG TI Molecular basis of the VHL hereditary cancer syndrome SO NATURE REVIEWS CANCER LA English DT Review ID VON-HIPPEL-LINDAU; TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; CENTRAL-NERVOUS-SYSTEM; PROTEIN-KINASE-C; BIOLOGICALLY-ACTIVE PRODUCT; UBIQUITIN LIGASE COMPLEX; FACTOR RECEPTOR ANTIBODY AB The von Hippel-Lindau hereditary cancer syndrome was first described about 100 years ago, The unusual clinical features of this disorder predicted a role for the von Hippel-Lindau gene (VHL) in the oxygen-sensing pathway. Indeed, recent studies of this gene have helped to decipher how cells sense changes in oxygen availability, and have revealed a previously unappreciated role of prolyl hydroxylation in intracellular signalling. These studies, in turn, are laying the foundation for the treatment of a diverse set of disorders, including cancer, myocardial infarction and stroke. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 144 TC 463 Z9 479 U1 4 U2 29 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 SEP PY 2002 VL 2 IS 9 BP 673 EP 682 DI 10.1038/nrc885 PG 10 WC Oncology SC Oncology GA 636GZ UT WOS:000180447400013 PM 12209156 ER PT J AU Li, E AF Li, E TI Chromatin modification and epigenetic reprogramming in mammalian development SO NATURE REVIEWS GENETICS LA English DT Review ID X-CHROMOSOME INACTIVATION; EMBRYONIC STEM-CELLS; POLYCOMB-GROUP GENE; HISTONE DEACETYLASE COMPLEX; DNA METHYLATION; DE-NOVO; MOUSE EMBRYO; PREIMPLANTATION DEVELOPMENT; TRANSCRIPTIONAL REPRESSOR; IMPRINTED EXPRESSION AB The developmental programme of embryogenesis is controlled by both genetic and epigenetic mechanisms. An emerging theme from recent studies is that the regulation of higher-order chromatin structures by DNA methylation and histone modification is crucial for genome reprogramming during early embryogenesis and gametogenesis, and for tissue-specific gene expression and global gene silencing. Disruptions to chromatin modification can lead to the dysregulation of developmental processes, such as X-chromosome inactivation and genomic imprinting, and to various diseases. Understanding the process of epigenetic reprogramming in development is important for studies of cloning and the clinical application of stem-cell therapy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. RP Li, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, 149 13th St, Charlestown, MA 02129 USA. NR 128 TC 1127 Z9 1187 U1 21 U2 163 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD SEP PY 2002 VL 3 IS 9 BP 662 EP 673 DI 10.1038/nrg887 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 589WZ UT WOS:000177785700013 PM 12209141 ER PT J AU Friedrich, SW Lin, SC Stoll, BR Baxter, LT Munn, LL Jain, RK AF Friedrich, SW Lin, SC Stoll, BR Baxter, LT Munn, LL Jain, RK TI Antibody-directed effector cell therapy of tumors: Analysis and optimization using a physiologically based pharmacokinetic model SO NEOPLASIA LA English DT Article DE bifunctional antibody; lymphocyte; trafficking; mathematical model; tumor localization ID BIFUNCTIONAL ANTIBODIES; BISPECIFIC ANTIBODY; ADOPTIVE IMMUNOTHERAPY; CANCER-PATIENTS; BLOOD-VESSELS; T-CELLS; LYMPHOCYTES; METASTASES; XENOGRAFTS; LYMPHOMA AB The failure of the cellular immune response to stop solid tumor growth has been the subject of much research. Although the mechanisms for tumor evasion of immune response are poorly understood, one viable explanation is that tumor-killing lymphocytes cannot reach the tumor cells in sufficient quantity to keep the tumor in check. Recently, the use of bifunctional antibodies (BFAs) has been proposed as a way to direct immune cells to the tumor: one arm of the antibody is specific for a known tumor-associated antigen and the other for a lymphocyte marker such as CD3. Injecting this BFA should presumably result in cross-linking of lymphocytes (either endogenous or adoptively transferred) with tumor cells, thereby enhancing therapy. Results from such an approach, however, are often disappointing - frequently there is no benefit gained by using the BFA. We have analyzed the retargeting of endogenous effector cells by BFA using a physiologically based whole-body pharmacokinetic model that accounts for interactions between all relevant species in the various organs and tumor. Our results suggest that the design of the BFA is critical and the binding constants of the antigen and lymphocyte binding epitopes need to be optimized for successful therapy. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox-7, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [P01 CA080124, P01 CA80124]; NHLBI NIH HHS [R01 HL064240, R01 HL64240] NR 29 TC 27 Z9 27 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD SEP-OCT PY 2002 VL 4 IS 5 BP 449 EP 463 DI 10.1038/sj.neo.7900260 PG 15 WC Oncology SC Oncology GA 589GB UT WOS:000177749500010 PM 12192604 ER PT J AU Taylor, AN Tritt, SH Tio, DL Romeo, HE Yirmiya, R AF Taylor, AN Tritt, SH Tio, DL Romeo, HE Yirmiya, R TI Maternal adrenalectomy abrogates the effect of fetal alcohol exposure on the interleukin-1 beta-induced febrile response: Gender differences SO NEUROENDOCRINOLOGY LA English DT Article DE adrenalectomy; body temperature; interleukins; thermoregulation; sex dimorphism; stress; fever; fetal differentiation; alcohol exposure ID PRENATAL ALCOHOL; INDUCED FEVER; RATS; CYTOKINES; IMMUNE; DAMS; CORTICOSTERONE; THERMOGENESIS; SECRETION; PREGNANCY AB Fetal alcohol exposure (FAE) has been shown to blunt the febrile component of the primary host-defense response to infection induced experimentally by systemic administration of interleukin (IL)-1beta. Given that maternal adrenalectomy (ADX) can prevent various postnatal effects of FAE, the present experiments were designed to determine whether maternal ADX would prevent the blunted IL-1beta-induced febrile response of fetal alcohol-exposed offspring and whether the effects of maternal ADX would be gender related. Timed-pregnant rats underwent ADX or were sham-operated on gestation day (GD) 7, or remained intact (without any surgery), and were fed ethanol-containing (E) or pair-fed (PF) liquid diets or normal (N) rat chow and water from GD 8 to GD 21. As adults, male and female E, PF and N offspring were injected with saline on day 1 and with IL-1beta (2 mug/ kg, i.p.) on day 2 at 09.00 h and the body temperature was recorded biotelemetrically for 8.5 h. IL-1beta produced significantly lower febrile responses in female than in male offspring of intact dams, irrespective of prenatal diet. Furthermore, prenatal surgical stress differentially affected the IL-1beta-induced febrile response of male and female normally fed offspring. Additionally, in both male and female offspring of intact dams, FAE significantly attenuated the IL-1beta-induced febrile response. In males, FAE also attenuated the febrile response in the offspring of maternal sham-operated dams, and this effect was completely reversed by maternal ADX In females, both maternal sham surgery and ADX reversed the effect of FAE on the febrile response. These findings suggest that maternal adrenal mediators are essential for the longterm effect of FAE on the febrile response in male offspring. In females, early prenatal surgical stress is sufficient to reverse the effects of FAE, possibly via adrenalin-dependent mechanisms that affect the thermoregulatory system. Copyright (C) 2002 S. KargerAG, Basel. 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. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Hebrew Univ Jerusalem, Dept Psychol, Jerusalem, Israel. RP Taylor, AN (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NIAAA NIH HHS [AA09850] NR 25 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD SEP PY 2002 VL 76 IS 3 BP 185 EP 192 DI 10.1159/000064524 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 596PY UT WOS:000178174300006 PM 12218351 ER PT J AU Badgaiyan, RD Schacter, DL Alpert, NM AF Badgaiyan, RD Schacter, DL Alpert, NM TI Retrieval of relational information: A role for the left inferior prefrontal cortex SO NEUROIMAGE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; EPISODIC MEMORY RETRIEVAL; MEDIAL TEMPORAL-LOBE; DECLARATIVE MEMORY; FUNCTIONAL MRI; HIPPOCAMPAL-FORMATION; RECOGNITION MEMORY; WORKING-MEMORY; PET ACTIVATION; BRAIN ACTIVITY AB Neuroiniaging studies have implicated different areas of prefrontal cortex and medial temporal lobe structures (MTL) in episodic retrieval tasks. However, the role of specific regions in particular aspects of episodic memory is still unclear. In this experiment we studied changes in regional cerebral blood flow (rCBF) associated with relational and nonrelational retrieval of studied pairs of words. For relational retrieval, a list of either studied or rearranged pairs was presented and subjects (n = 8) were asked to indicate whether pairs had appeared on the study list. Under the nonrelational retrieval condition they indicated whether one or both words of the pair had appeared on the study list. As compared to the baseline condition (looking at a cross-mark), increased rCBF was observed in the left inferior prefrontal cortex (LIPFC) for both studied pairs and rearranged pairs under the relational retrieval condition. Under the nonrelational condition, an increase was observed in right inferior frontal gyrus. The MTL showed a trend for increased rCBF in the rearranged-pair condition. This increase was probably associated with the encoding that accompanies retrieval of novel stimuli. Results suggest that the lateralized activation of prefrontal cortex observed in episodic memory tasks may be related to the degree of relational processing involved. The LIPFC appears to be associated with relational retrieval and the right prefrontal cortex with nonrelational retrieval. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Dept Psychol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, PET Imaging Lab, Boston, MA 02114 USA. RP Badgaiyan, RD (reprint author), Harvard Univ, William James Hall,Room 875,33,Kirkland St, Cambridge, MA 02138 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [MH57915, MH60941] NR 60 TC 26 Z9 26 U1 3 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2002 VL 17 IS 1 BP 393 EP 400 DI 10.1006/nimg.2002.1219 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 595HD UT WOS:000178102000029 PM 12482092 ER PT J AU Jarus-Dziedzic, K Juniewicz, H Wronski, J Zub, WL Kasper, E Gowacki, M Mierzwa, J AF Jarus-Dziedzic, K Juniewicz, H Wronski, J Zub, WL Kasper, E Gowacki, M Mierzwa, J TI The relation between cerebral blood flow velocities as measured by TCD and the incidence of delayed ischemic deficits. A prospective study after subarachnoid hemorrhage SO NEUROLOGICAL RESEARCH LA English DT Article DE delayed ischemic deficit; vasospasm; transcranial Doppler ultrasonography ID TRANSCRANIAL DOPPLER ULTRASONOGRAPHY; INDUCED HYPERTENSION; VASOSPASM; SONOGRAPHY; ULTRASOUND; DIAGNOSIS; HEMODYNAMICS; NIMODIPINE; TOMOGRAPHY; MANAGEMENT AB Patients (n = 127) with aneurysmal subarachnoid hemorrhage (SAH) were examined by transcranial Doppler ultrasonography (TCD) in a prospective study to follow the time course of the posthemorthagic blood flow velocity in both the middle cerebral artery (MCA) and in the anterior cerebral artery (ACA). Results were analysed to reveal their relationship and predictive use with respect to the occurrence of delayed ischemic deficits. Mean flow velocities (MTV) higher than 120 cm sec(-1) in MCA and 90 cm sec(-1) in ACA were interpreted as indicative for significant vasospasm. In 20 of our 127 patients (16%) a delayed ischemic deficit (DID) was subsequently diagnosed clinically (DID+ group). Patients in the DID+ group can be characterized as those individuals who presented early during the observation period post-SAH with highest values of MFV, a faster increase and longer persistence of pathologically elevated MFV-values (exceeding 120 cm sec(-1) in MCA and 90 cm sec(-1) in ACA). They also show a greater difference in MFV-values if one compares the operated to the nonoperated side. Differences in MFV-values obtained in MCA or ACA were statistically significant (p < 0.05) for DID+ and DID- patients. The daily maximal increase of MFV was found between days 9 and 11 after SAH. In the DID+ group, the maximal MFV was 181+/-26 cm sec(-1) in MCA and 119+/-14 cm sec(-1) in ACA. In contrast to this, patients in the DID- group were found to present with MFV of 138+/-11 cm sec(-1) in MCA and 100+/-7 cm sec(-1) in ACA respectively. Delayed ischemic deficits appeared three times more often in DID+ patients than in patients with MFV < 120 cm sec(-1), if they showed a MFV > 120 cm sec(-1) in MCA. If pathological values were obtained in ACA, this ratio increases to about four times, if DID+ patients presented with MFV > 90 cm sec(-1) versus patients with MFV < 90 cm sec(-1). Daily monitoring of vasospasm using TCD examination is thus helpful to identify patients at high risk for delayed ischemic deficits. This should allow us to implement further preventive treatment regimens. C1 Polish Acad Sci, Med Res Ctr, Dept Neurosurg, PL-01809 Warsaw, Poland. Univ Technol Wroclaw, Fac Elect, Wroclaw, Poland. Wroclaw Med Acad, Dept Neurosurg, Wroclaw, Poland. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Jarus-Dziedzic, K (reprint author), Polish Acad Sci, Med Res Ctr, Dept Neurosurg, Ceglowska 80, PL-01809 Warsaw, Poland. NR 50 TC 15 Z9 16 U1 0 U2 0 PU FOREFRONT PUBL GROUP PI WILTON PA C/O MARY J RAWLINS, 5 RIVER RD, STE 113, WILTON, CT 06897 USA SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD SEP PY 2002 VL 24 IS 6 BP 582 EP 592 DI 10.1179/016164102101200393 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 606WD UT WOS:000178756900011 PM 12238625 ER PT J AU Cohen, LS Miner, C Brown, E Freeman, EW Halbreich, U Sundell, K McCray, S AF Cohen, LS Miner, C Brown, E Freeman, EW Halbreich, U Sundell, K McCray, S TI Premenstrual daily fluoxetine for premenstrual dysphoric disorder: A placebo-controlled, clinical trial using computerized diaries SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PHASE SERTRALINE TREATMENT; LUTEAL-PHASE; DOUBLE-BLIND; WOMEN; EXPERIENCE; CROSSOVER; CYCLE AB OBJECTIVE: To evaluate premenstrual daily dosing with fluoxetine for treatment of premenstrual dysphoric disorder. METHODS: After a two-cycle screening and one-cycle single-blind placebo period, 260 women were randomized to fluoxetine 10 mg, fluoxetine 20 mg, or placebo (dosed daily from 14 days before next expected menses through the first fall day of bleeding) for three cycles. Women recorded premenstrual dysphoric disorder symptoms daily using a computerized version of the Daily Record of Severity of Problems. RESULTS: Premenstrual daily fluoxetine 20 mg demonstrated significant improvement in mean Daily Record of Severity of Problems luteal scores compared with placebo (P = .005); premenstrual daily fluoxetine 10 mg did not (P = .100). Daily Record of Severity of Problems total scores were statistically significantly improved by the first treatment cycle for both active treatment groups. However, only fluoxetine 20 mg remained statistically significantly superior to placebo throughout the active treatment phase of the trial. Both fluoxetine groups showed significant treatment advantage over placebo for mood-related symptoms (P < .05). Only premenstrual daily fluoxetine 20 mg showed significant treatment advantage over placebo for physical symptoms of breast tenderness (P < .001), bloating (P = .001), and joint/muscle pain (P = .037). Treatment was well tolerated; discontinuations due to adverse events did not differ among the three groups (P = .316). CONCLUSION: Premenstrual daily dosing with fluoxetine effectively treats mood, physical, and social functioning symptoms associated with premenstrual dysphoric disorder. Fluoxetine 20 mg appears to have comparable tolerability with, and better efficacy than, fluoxetine 10 mg. (C) 2002 by The American College of Obstetricians and Gynecologists. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA. RP Cohen, LS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, WAC 815, Boston, MA 02114 USA. NR 24 TC 83 Z9 86 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 SEP PY 2002 VL 100 IS 3 BP 435 EP 444 AR PII S0029-7844(02)02166-X DI 10.1016/S0029-7844(02)02166-X PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 588FN UT WOS:000177691500007 PM 12220761 ER PT J AU Hughes, KS AF Hughes, KS TI Resection of liver metastases: State of the art - The Ravikumar/Gallos article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD SEP PY 2002 VL 16 IS 9 BP 1260 EP + PG 2 WC Oncology SC Oncology GA 601JX UT WOS:000178443500019 ER PT J AU Rizzo, JF Andreoli, CM Rabinow, JD AF Rizzo, JF Andreoli, CM Rabinow, JD TI Use of magnetic resonance imaging to differentiate optic neuritis and nonarteritic anterior ischemic optic neuropathy SO OPHTHALMOLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; FLUORESCEIN ANGIOGRAPHY; NERVE; CORTICOSTEROIDS; LESIONS; SERIAL; TRIAL AB Objective: To determine if magnetic resonance imaging (MRI) of the optic nerves obtained during the acute phase can distinguish patients with optic neuritis (ON) from those with nonarteritic anterior ischemic optic neuropathy (NAION). Design: Retrospective, neuroradiologic, observational study. Participants: Sixty-four patients diagnosed as having either ON or NAION who were diagnosed by clinical criteria and imaged by MRI. Methods: Demographic information on the MRI scans was masked and the patients were presented randomly and in a blinded fashion to a neuroradiologist (JDR) for determination of abnormalities. Reproducibility was assessed by presenting 10 of the scans a second time to the same neuroradiologist. Main Outcome Measures: The presence or absence and location of abnormal MRI signals of the optic nerve. Results: Evaluation of reproducibility revealed identical interpretations of the ten scans submitted a second time. The optic nerve was abnormal in the clinically affected eye in 31 of the 32 ON patients but in only 5 of the 32 NAION patients. Thirty of the 31 ON patients who received gadolinium had enhancement, and 27 of the 32 ON patients had increased short T-1 inversion recovery signal in the clinically affected optic nerve. The five NAION patients with abnormal scans in the clinically affected eye had increased short T-1 inversion recovery signal, and in two of these, there also was enhancement of the optic nerve. For the ON patients, enhancement involved the entire length of the intraorbital optic nerve in 18 cases and the intracranial segment of the optic nerve in 19 cases. Conclusions: Our study shows that MRI scanning of the optic nerve shows significantly different results between patients clinically diagnosed with either ON or NAION. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Rizzo, JF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 27 TC 53 Z9 54 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2002 VL 109 IS 9 BP 1679 EP 1684 AR PII S0161-6420(02)01148-X DI 10.1016/S0161-6420(02)01148-X PG 6 WC Ophthalmology SC Ophthalmology GA 592CT UT WOS:000177919700028 PM 12208717 ER PT J AU Aiello, LP George, DJ Cahill, MT Wong, JS Cavallerano, J Hannah, AL Kaelin, WG AF Aiello, LP George, DJ Cahill, MT Wong, JS Cavallerano, J Hannah, AL Kaelin, WG TI Rapid and durable recovery of visual function in a patient with von Hippel-Lindau syndrome after systemic therapy with vascular endothelia growth factor receptor inhibitor SU5416 SO OPHTHALMOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; PERMEABILITY FACTOR; IN-VIVO; RETINAL NEOVASCULARIZATION; SELECTIVE INHIBITOR; CLINICAL-FEATURES; DISEASE; HEMANGIOBLASTOMA; PHOTOCOAGULATION; HEMANGIOMAS AB Purpose: To present a case of rapid and durable recovery of visual function in a patient with von Hippel-Lindau syndrome and optic nerve head hemangioblastoma after systemic treatment with the vascular endothelial growth factor (VEGF) receptor inhibitor SU5416. Design: Interventional case report. Methods: Visual function parameters, including visual acuity, automated visual field, and contrast sensitivity, were evaluated using standardized methods repeatedly over a 15-month period. Fundus photographs and fluorescein angiograms were also obtained. Central nervous system lesions were monitored by computed tomography (CT) and magnetic resonance imaging (MRI) scans. Treatment involved the systemic administration of the VEGF receptor inhibitor SU5416. Main Outcome Measures: Clinical presentation, visual acuity using Early Treatment Diabetic Retinopathy Study protocol, Humphrey automated perimetry, (Zeiss Humphrey Systems, Dublin, CA) Vistech contrast sensitivity (Vistech Consultants Inc., Dayton, OH) Farnsworth (Farnsworth-Munsell Color Services, New Windsor, NY) dichotomous panel D-15, retinal photography, fluorescein angiography, and CT and MRI scans. Results: Within 4 weeks of therapy, visual acuity had improved from 20/32(-2) to 20/16(-1), the visual field had expanded from being circumferentially constricted to within 8degrees of fixation to normal, and contrast sensitivity improved in all but the lowest spatial frequency (1.5 cycles/degree). No change was observed in lesion size by fundus photography. Improvement has been maintained over 18 months with intermittent SU5416 therapy. Conclusions: We report rapid, extensive, and durable recovery of visual function after systemic administration of the VEGF receptor inhibitor SU5416 to a patient with VHL syndrome and optic nerve head hemangioblastoma. These findings suggest that continued evaluation of VEGF inhibitors for ocular neovascular disorders is warranted. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. SUGEN Inc, San Francisco, CA USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 41 TC 68 Z9 71 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2002 VL 109 IS 9 BP 1745 EP 1751 AR PII S0161-6420(02)01159-4 DI 10.1016/S0161-6420(02)01159-4 PG 7 WC Ophthalmology SC Ophthalmology GA 592CT UT WOS:000177919700037 PM 12208726 ER PT J AU Pierce, MC Park, BH Cense, B de Boer, JF AF Pierce, MC Park, BH Cense, B de Boer, JF TI Simultaneous intensity, birefringence, and flow measurements with high-speed fiber-based optical coherence tomography SO OPTICS LETTERS LA English DT Article ID VIVO HUMAN SKIN; BLOOD-FLOW; DOPPLER TOMOGRAPHY; INTERFEROMETER AB We demonstrate that tissue structure, birefringence, and blood flow can be imaged simultaneously by use of techniques of polarization-sensitive optical coherence tomography and phase-resolved optical Doppler tomography. An efficient data-acquisition procedure is implemented that optimizes the concurrent processing and display of all three image types. Images of in vivo human skin acquired with a high-speed fiber-based system are presented. (C) 2002 Optical Society of America. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 18 TC 67 Z9 68 U1 0 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD SEP PY 2002 VL 27 IS 17 BP 1534 EP 1536 DI 10.1364/OL.27.001534 PG 3 WC Optics SC Optics GA 588FX UT WOS:000177692400012 PM 18026497 ER PT J AU Cense, B Chen, TC Park, BH Pierce, MC de Boer, JF AF Cense, B Chen, TC Park, BH Pierce, MC de Boer, JF TI In vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer by polarization-sensitive optical coherence tomography SO OPTICS LETTERS LA English DT Article ID THICKNESS AB To our knowledge, this is the first demonstration of in vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer (RNFL) by use of polarization-sensitive optical coherence tomography (PS-OCT). Because glaucoma causes nerve fiber layer damage, which may cause loss of retinal birefringence, PS-OCT is a potentially useful technique for the early detection of glaucoma. We built a fiber-based PS-OCT setup that produces quasi-real-time images of the human retina in vivo. Preliminary measurements of a healthy volunteer showed that the double-pass phase retardation per unit depth of the RNFL near the optic nerve head is 39 +/- 6degrees/100 mum. (C) 2002 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Cense, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, BAR 714, Boston, MA 02114 USA. RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 14 TC 126 Z9 129 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD SEP PY 2002 VL 27 IS 18 BP 1610 EP 1612 DI 10.1364/OL.27.001610 PG 3 WC Optics SC Optics GA 592PD UT WOS:000177945300008 PM 18026517 ER PT J AU Ntziachristos, V Ripoll, J Weissleder, R AF Ntziachristos, V Ripoll, J Weissleder, R TI Would near-infrared fluorescence signals propagate through large human organs for clinical studies? (vol 27, pg 333, 2002) SO OPTICS LETTERS LA English DT Correction C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Crete, Greece. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. OI Ripoll, Jorge/0000-0001-8856-7738 NR 1 TC 11 Z9 12 U1 1 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD SEP PY 2002 VL 27 IS 18 BP 1652 EP 1652 DI 10.1364/OL.27.001652 PG 1 WC Optics SC Optics GA 592PD UT WOS:000177945300022 PM 18026531 ER PT J AU Fechner, FP Cunningham, MJ Eavey, RD AF Fechner, FP Cunningham, MJ Eavey, RD TI Laser therapy for refractory myringitis in children SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID GRANULAR MYRINGITIS AB OBJECTIVE: We present the application and initial, results of a CO2 laser technique for the treatment of medically refractory chronic granular myringitis (CGM). STUDY DESIGN AND SETTING: Retrospective case series of 15 treated ears in 13 consecutive patients between the ages of 6 and 14 years (median age, 9.0 years) cared for in a tertiary care specialty hospital. RESULTS., Eleven of 15 treated ears had total resolution of CGM and associated symptoms; median follow-up time was 10 months. Three ears were improved, and 1 ear remained unchanged. Three of 5 preoperative tympanic membrane perforations healed after laser treatment; 1 patient developed a postoperative, dry perforation. Hearing was not impaired in any patient tested. CONCLUSION: Preliminary results suggest that CGM, when refractory to medical treatment, can often be treated effectively by a single laser treatment. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles S, Boston, MA 02114 USA. NR 12 TC 5 Z9 5 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 SEP PY 2002 VL 127 IS 3 BP 163 EP 168 DI 10.1067/mhn.2002.127628 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 596MQ UT WOS:000178169000006 PM 12297805 ER PT J AU Hurst, DS Gordon, BR Krouse, JH AF Hurst, DS Gordon, BR Krouse, JH TI The importance of glycerin-containing negative control tests in allergy research studies that use intradermal skin tests SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngic-Allergy CY SEP 22, 2000 CL WASHINGTON, D.C. SP Amer Acad Otolaryngic Allergy ID HISTAMINE-RELEASE; MAJOR ALLERGENS; VARIABILITY; DIAGNOSIS; CHALLENGE; RHINITIS; ASTHMA AB OBJECTIVE: We sought to assess skin whealing with glycerin-containing control injections for intradermal skin tests. DESIGN: Observational. METHODS: Wheal sizes were measured at 0, 10, and 15 minutes after intradermal injection of 0.01 and 0.02 mL of phenolated normal saline and 0.5% and 5% concentrations of glycerin in the same quantity of phenolated saline. RESULTS: Intradermal injection of 0.01 ml. of phenolated saline produced an average 4.9-mm wheal, which expanded to 5.2 mm at 10 minutes and to 6.0 mm at 15 minutes'. Intradermal injection of 0.02 ml. of phenolated saline produced a 6.4-mm wheal, which expanded to 7.0 mm at 10 minutes and 8.0 mm at 15 minutes. The addition of glycerin produced proportionally larger wheals. CONCLUSIONS: Because glycerin increases whealing beyond that with phenolated saline, skin tests containing glycerin must be compared with glycerin-containing negative controls. Intradermal skin tests that fail to compare findings in this manner contain an inherent methodologic flaw and are uninterpretable. C1 Tufts Univ, Boston, MA 02111 USA. Harvard Univ, Dept Otolaryngol & Laryngol, Cambridge, MA 02138 USA. Massachusetts Eye & Ear Infirm, Hyannis, MA USA. Cape Code Hosp, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. RP Hurst, DS (reprint author), 136 Hurst Lane, Farmington, ME 04938 USA. NR 25 TC 12 Z9 12 U1 0 U2 1 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 SEP PY 2002 VL 127 IS 3 BP 177 EP 181 DI 10.1067/mhn.2002.127890 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 596MQ UT WOS:000178169000008 PM 12297807 ER PT J AU McKenna, MJ Kristiansen, AG Tropitzsch, AS Tranebjaerg, L Merchant, SN AF McKenna, MJ Kristiansen, AG Tropitzsch, AS Tranebjaerg, L Merchant, SN TI Deoxyribonucleic acid contamination in archival human temporal bones: A potentially significant problem SO OTOLOGY & NEUROTOLOGY LA English DT Article DE deoxyribonucleic acid; contamination; archival human temporal bones; polymerase chain reaction ID POLYMERASE CHAIN-REACTION; REACTION AMPLIFICATION; MENTAL DEFICIENCY; DNA; SECTIONS; PATHOLOGY; BLINDNESS; SPECIMENS; DYSTONIA; SEQUENCE AB Hypothesis: Contamination of archival human temporal bones with extraneous deoxyribonucleic acid may represent a potentially significant problem in the analysis of nucleic acids isolated from archival specimens. Background: During the past decade, there has been growing interest in the development of molecular biologic techniques that can be applied to the investigation of pathologic changes in archival human temporal bones. The impetus for the development of these techniques is in part related to the fact that the temporal bone collections represent a repository of archival material compiled over decades, which is not available from living patients. Methods: An archival human temporal bone specimen from a male patient with the Mohr-Tranebjaerg syndrome (formerly called DFN-1) and a well-characterized mutation was analyzed for the presence of the mutation by a standard method for extraction, isolation, amplification, and sequencing of deoxyribonucleic acid. The experiment was repeated four times. Results: The deoxyribonucleic acid sequence from three of four extractions was normal. The known mutation was easily and repeatedly demonstrated in a blood sample from the same individual. Because Mohr-Tranebjaerg syndrome is X-linked, there is only one allele, and therefore there is no potential endogenous source to account for the normal sequence that was amplified. Contamination of the tissue sections by extraneous deoxyribonucleic acid presumably occurred during acquisition and processing of the temporal bone. Conclusions: Contamination of archival temporal bones with exogenous deoxyribonucleic acid is a significant potential problem that must be considered in the interpretation of the results of deoxyribonucleic acid retrieved from archival sections. The authors recommend collecting blood samples from temporal bone donors in the future to ensure the availability of a reliable source of deoxyribonucleic acid. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Univ Tubingen, Dept Otorhinolaryngol, Tubingen, Germany. Bispebjerg Hosp, Dept Audiol, DK-2400 Copenhagen, Denmark. Univ Copenhagen, Planum Inst, Dept Med Genet, Copenhagen, Denmark. RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [5 R01 DC03401] NR 19 TC 4 Z9 4 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD SEP PY 2002 VL 23 IS 5 BP 789 EP 792 DI 10.1097/00129492-200209000-00030 PG 4 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 592BZ UT WOS:000177918000032 PM 12218636 ER PT J AU Ehrhart, J Gluck, M Mieyal, J Zeevalk, GD AF Ehrhart, J Gluck, M Mieyal, J Zeevalk, GD TI Functional glutaredoxin (thioltransferase) activity in rat brain and liver mitochondria SO PARKINSONISM & RELATED DISORDERS LA English DT Article; Proceedings Paper CT 14th International Congress on Parkinsons Disease CY JUL 28-31, 2001 CL HELSINKI, FINLAND DE glutathione; mitochondria; Parkinson's disease; protein-glutathione mixed disulfide; brain ID PROTEIN DISULFIDE-ISOMERASE; GLUTATHIONE MIXED DISULFIDE; IN-SITU HYBRIDIZATION; DNA-BINDING ACTIVITY; IMMUNOLOGICAL CHARACTERIZATION; THIOREDOXIN REDUCTASE; HEART-MITOCHONDRIA; HYDROGEN-PEROXIDE; THIOL HOMEOSTASIS; S-THIOLATION AB Glutaredoxin (Grx) is a specific and efficient catalyst of glutathione-dependent deglutathionylation of protein-SS-glutathione mixed disulfides. Grx has been identified in brain cytosol, but the presence of activity in subcellular organelles has not been reported. Increases in protein glutathionylation are likely to occur in mitochondria during oxidative stress and it is, therefore, important to know if this organelle contains the enzyme activity needed to reverse such protein thiolation. Grx-like activity in the PI supernatant from rat brain and liver was doubled in the presence of Triton-X 100 suggesting a releasable pool of Grx. Brain and liver homogenates were subfractionated into cytosolic, mitochondrial and microsomal fraction, their purity determined by biochemical assay and EM and assayed for Grx-like activity. The data presented demonstrate that mitochondria contain functional Grx-like activity. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 UMDNJ, Robert Wood Johnson Med Sch, Dept Neurol, Piscataway, NJ 08854 USA. Bronx Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. RP Ehrhart, J (reprint author), UMDNJ, Robert Wood Johnson Med Sch, Dept Neurol, Bldg UBHC,Room D-437-E-675 Hoes Lane, Piscataway, NJ 08854 USA. FU NIA NIH HHS [AG15885]; NINDS NIH HHS [NS36157] NR 50 TC 17 Z9 17 U1 0 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 SEP PY 2002 VL 8 IS 6 BP 395 EP 400 AR PII S1353-8020(02)00020-2 DI 10.1016/S1353-8020(02)00020-2 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 593MK UT WOS:000177995100004 PM 12217626 ER PT J AU Pinar, H Stephens, M Singer, DB Boyd, TK Pflueger, SMV Gang, DL Roberts, DJ Sung, CJ AF Pinar, H Stephens, M Singer, DB Boyd, TK Pflueger, SMV Gang, DL Roberts, DJ Sung, CJ TI Triplet placentas: Reference values for weights SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE in vitro fertilization; multiple birth; placenta; triplet; twin; weight ID PREGNANCIES AB The occurrence of twins, triplets, and other multiple births increased significantly between 1970 and 2000 in the United States and other industrialized countries. The number of triplet placentas submitted for examination as pathologic specimens has also markedly increased, but no reference values are published for triplet Weights. We examined 196 normal triplet placentas. Specimens with associated conditions known to affect the weights of the placentas were excluded. The gestational ages ranged between 20 and 38 weeks. Mean weights for different gestational ages are summarized as follows: 253 g for 20 weeks, 319 g for 22 weeks, 406 g for 24 weeks, 509 g for 26 weeks, 621 g for 28 weeks, 738 g for 30 weeks, 855 g for 32 weeks, 965 g for 34 weeks, 1065 g for 36 weeks, and 1147 g for 38 weeks. Weight gain of triplet placentas appears to parallel that of twin placentas. The mean values of placental Weights for triplets at each gestational age are less than triple those of singleton weights for the same duration of gestation. The placental weights in multiple gestations do not increase proportionately with the number of fetuses. C1 Women & Infants Hosp Rhode Isl, Dept Pathol & Lab Med, Div Perinatal & Pediat Pathol, Providence, RI 02905 USA. Brown Univ, Sch Med, Providence, RI 02905 USA. Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02905 USA. Baystate Med Ctr, Dept Pathol & Lab Med, Springfield, MA 01199 USA. Tufts Univ, Sch Med, Springfield, MA 01199 USA. Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Pinar, H (reprint author), Women & Infants Hosp Rhode Isl, Dept Pathol & Lab Med, Div Perinatal & Pediat Pathol, 101 Dudley St, Providence, RI 02905 USA. NR 8 TC 10 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD SEP-OCT PY 2002 VL 5 IS 5 BP 495 EP 498 DI 10.1007/s10024-002-0014-0 PG 4 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 602MB UT WOS:000178508100009 PM 12202997 ER PT J AU Gidwani, PP Sobol, A DeJong, W Perrin, JM Gortmaker, SL AF Gidwani, PP Sobol, A DeJong, W Perrin, JM Gortmaker, SL TI Television viewing and initiation of smoking among youth SO PEDIATRICS LA English DT Article DE smoking; adolescents; television; youth smoking ID HEALTH-RISK BEHAVIORS; ADOLESCENT HEALTH; PHYSICAL-ACTIVITY; US ADOLESCENTS; UNITED-STATES; CHILDREN; TOBACCO; VALIDITY; ALCOHOL AB Background. Smoking is the leading preventable cause of death in the United States, and the risk of disease increases the earlier in life smoking begins. The prevalence of smoking among US adolescents has increased since 1991. Despite bans on television tobacco advertising, smoking on television remains widespread. Objective. To determine whether youth with greater exposure to television viewing exhibit higher rates of smoking initiation. Methods. We used the National Longitudinal Survey of Youth, Child Cohort to examine longitudinally the association of television viewing in 1990 among youth ages 10 to 15 years with smoking initiation from 1990-1992. Television viewing was based on the average of youth and parent reports. We used multiple logistic regression, taking into account sampling weights, and controlled for ethnicity; maternal education, IQ, and work; household structure; number of children; household poverty; child gender; and child aptitude test scores. Results. Among these youth, smoking increased from 4.8% in 1990 to 12.3% in 1992. Controlling for baseline characteristics, youth who watched 5 or more hours of TV per day were 5.99 times more likely to initiate smoking behaviors (95% confidence interval: 1.39-25.71) than those youth who watched <2 hours. Similarly, youth who watched >4 to 5 hours per day were 5.24 times more likely to initiate smoking than youth who watched <2 hours (95% confidence interval: 1.19-23.10). Conclusions. Television viewing is associated in a dose-response relationship with the initiation of youth smoking. Television viewing should be included in adolescent risk behavior research. Interventions to reduce television viewing may also reduce youth smoking initiation. C1 Childrens Hosp & Hlth Ctr, Ctr Child Hlth Outcomes, San Diego, CA 92123 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Gidwani, PP (reprint author), Childrens Hosp & Hlth Ctr, Ctr Child Hlth Outcomes, 3020 Childrens Way,MC 5053, San Diego, CA 92123 USA. FU AHRQ HHS [T32 HS00063]; ODCDC CDC HHS [U48/CCU115807] NR 32 TC 86 Z9 86 U1 2 U2 17 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 SEP PY 2002 VL 110 IS 3 BP 505 EP 508 DI 10.1542/peds.110.3.505 PG 4 WC Pediatrics SC Pediatrics GA 589MN UT WOS:000177762900017 PM 12205251 ER PT J AU Levin, LA Gordon, LK AF Levin, LA Gordon, LK TI Retinal ganglion cell disorders: types and treatments SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review ID OPTIC-NERVE HEAD; OPEN-ANGLE GLAUCOMA; NITRIC-OXIDE SYNTHASE; LATERAL GENICULATE-NUCLEUS; NORMAL-TENSION GLAUCOMA; METABOTROPIC GLUTAMATE-RECEPTOR; ELEVATED INTRAOCULAR-PRESSURE; RETROGRADE AXONAL-TRANSPORT; NEUROTROPHIC FACTOR BDNF; CALCIUM-BINDING PROTEIN C1 Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53792 USA. Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Hosp, Los Angeles, CA USA. RP Levin, LA (reprint author), Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, 600 Highland Ave, Madison, WI 53792 USA. FU NEI NIH HHS [EY12492, EY13708] NR 268 TC 32 Z9 32 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD SEP PY 2002 VL 21 IS 5 BP 465 EP 484 AR PII S1350-9462(02)00012-5 DI 10.1016/S1350-9462(02)00012-5 PG 20 WC Ophthalmology SC Ophthalmology GA 601HK UT WOS:000178440300003 PM 12207946 ER PT J AU Klein, CE Tangen, CM Braun, TJ Hussain, MHA Peereboom, DM Nichols, CR Rivkin, SE Dakhil, SR Crawford, ED AF Klein, CE Tangen, CM Braun, TJ Hussain, MHA Peereboom, DM Nichols, CR Rivkin, SE Dakhil, SR Crawford, ED TI SWOG-9510: Evaluation of topotecan in hormone refractory prostate cancer: A Southwest Oncology Group Study SO PROSTATE LA English DT Article DE hormone refractory prostate cancer; topotecan; clinical trial ID PHASE-II TRIAL; ORAL ESTRAMUSTINE; SOLID TUMORS; CHEMOTHERAPY; PACLITAXEL AB BACKGROUND. Prostate cancer is the most common malignancy in American men, and as many as 70%, of those initially treated for localized disease will ultimately progress and be considered candidates to receive therapy for metastatic cancer [1,2]. Although most will respond initially to hormone manipulation, essentially all will fail and require additional therapy. No standard chemotherapy approach has been shown to prolong survival significantly, and new agents are desperately needed. Topotecan is a now topoisomerase-1 inhibitor whose early investigation suggested possible activity in hormone-refractory prostate cancer. METHODS. In this phase II trial, patients having failed one or two prior androgen ablative therapies were treated with 21-day continuous intravenous infusions of topotecan at a dose of 0.5 mg/m(2) per day every 28 days. RESULTS. Twenty-six eligible patients were entered on the study. There were no confirmed tumor responses. Median survival was 9 months. The most common toxicities were hematologic, with 8 of 24 assessable patients experiencing grade 4 toxicity. CONCLUSION. Topotecan infusions at this dose are ineffective in the management of hormone-refractory prostate cancer. C1 Univ Colorado, Denver, CO 80202 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Wayne State Univ, Med Ctr, Detroit, MI 48202 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Puget Sound Oncol Consortium, Seattle, WA USA. Wichita Community Clin Oncol Program, Wichita, KS USA. RP Klein, CE (reprint author), Denver VAMC, 1055 Clermont St, Denver, CO 80220 USA. FU NCI NIH HHS [CA45560, CA04919, CA45807, CA63844, CA35281, CA58861, CA37981, CA12213, CA32102, CA46113, CA96429, CA38296, CA20319, CA76462, CA14028, CA35431] NR 19 TC 6 Z9 6 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 0270-4137 J9 PROSTATE JI Prostate PD SEP 1 PY 2002 VL 52 IS 4 BP 264 EP 268 DI 10.1002/pros.10118 PG 5 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 585TT UT WOS:000177541200002 PM 12210486 ER PT J AU Busch, B Biederman, J Cohen, LG Sayer, JM Monuteaux, MC Mick, E Zallen, B Faraone, SV AF Busch, B Biederman, J Cohen, LG Sayer, JM Monuteaux, MC Mick, E Zallen, B Faraone, SV TI Correlates of ADHD among children in pediatric and psychiatric clinics SO PSYCHIATRIC SERVICES LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Pediatrics/Ambulatory-Pediatric-Association/Society- for-Pediatric-Research CY MAY 12-16, 2000 CL BOSTON, MASSACHUSETTS SP Amer Acad Pediatr, Ambulat Pediatr Assoc, Soc Pediatr Res ID ATTENTION-DEFICIT HYPERACTIVITY; GREAT SMOKY MOUNTAINS; DEFICIT/HYPERACTIVITY DISORDER; PRIMARY-CARE; LEARNING-DISABILITIES; PSYCHOSOCIAL PROBLEMS; GENERAL-POPULATION; EMOTIONAL-PROBLEMS; COMMUNITY SAMPLE; COMORBIDITY AB Objective: Conventional wisdom among pediatricians has been that children with attention-deficit hyperactivity disorder (ADHD) who receive their diagnosis and are managed in the primary care setting have fewer comorbid psychiatric disorders and milder impairments than those seen in psychiatric clinics. The authors sought to determine whether comorbidity and clinical correlates of ADHD differ among children in these two settings. Methods: A case-control study design was used. Participants were 522 children and adolescents of both sexes, six to 18 years of age, with (N=280) and without (N=242) ADHD. Participants were drawn from pediatric and psychiatric clinics in a tertiary care hospital and a health maintenance organization in a large metropolitan area. Assessments were conducted with standardized measures of psychiatric, cognitive, social, academic, and family function. Results: The number, type, clusters, and a e at onset of ADHD symptoms were nearly identical for youths at pediatric and psychiatric ascertainment sources. Regardless of source, participants with ADHD were significantly more likely than controls to have a higher prevalence of mood disorders, other disruptive behavior, anxiety disorders, and substance use disorders. Significant impairments of intellectual, academic, interpersonal, and family functioning did not differ between ascertainment sources. Conclusions: Children with ADHD from both psychiatric and pediatric practices have prototypical symptoms of the disorder; high levels of comorbidity with mood, anxiety, and disruptive behavior disorders; and impairments in cognitive, interpersonal, and academic function that do not differ by ascertainment source. These findings suggest that children cared for in pediatric practice have similar levels of comorbidity and dysfunction as psychiatrically referred youth. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, WACC 725,15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD36317-02]; NIMH NIH HHS [R01-MH-50657-07] NR 60 TC 71 Z9 73 U1 0 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD SEP PY 2002 VL 53 IS 9 BP 1103 EP 1111 DI 10.1176/appi.ps.53.9.1103 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 590BH UT WOS:000177797000009 PM 12221308 ER PT J AU Cambray, J AF Cambray, J TI Who's really there? Dreams and the analytic third SO PSYCHOANALYTIC PSYCHOLOGY LA English DT Article AB Analysts from different theoretical orientations met to discuss dreams. A major focus was how unconscious processes symbolized in dreams impact the interactive field as viewed through the agency of the analytic third in conjunction with the quality of otherness that attends such experiences. Among the diverse offerings: exploring dreams through an ecopsychological lens, the clinical utility of a dream series in a post-Jungian analysis of I traumatized woman, and a Lacanian view on core elements of desire as used to reclaim the mysterious quality of dreams in showing forth the psyche together with clinical and cultural application of such ideas. A brief comparative analysis highlighting the role of the numinous in encounters with radical otherness is also offered. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. RP Cambray, J (reprint author), 311 Cole Ave, Providence, RI 02906 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0736-9735 J9 PSYCHOANAL PSYCHOL JI Psychoanal. Psychol. PD FAL PY 2002 VL 19 IS 4 BP 772 EP 776 DI 10.1037//0736-9735.19.4.772 PG 5 WC Psychology, Clinical; Psychology, Psychoanalysis SC Psychology GA 606KZ UT WOS:000178734300010 ER PT J AU McKay, JR Pettinati, HM Morrison, R Feeley, M Mulvaney, FD Gallop, R AF McKay, JR Pettinati, HM Morrison, R Feeley, M Mulvaney, FD Gallop, R TI Relation of depression diagnoses to 2-year outcomes in cocaine-dependent patients in a randomized continuing care study SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article ID ADDICTION SEVERITY INDEX; SUBSTANCE USE; FOLLOW-UP; PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; COPING SKILLS; ALCOHOLIC MEN; RELIABILITY; ABUSERS; DRINKING AB This study examined the relation between depression diagnoses and outcomes in 132 cocaine-dependent patients who were randomized to relapse prevention (RP) or standard 12-step focused group continuing care and followed for 2 years. Depressed patients attended more treatment sessions and had more cocaine-free urines during treatment than participants without depression, but they drank alcohol more frequently before treatment and during the 18-month posttreatment follow-up. Cocaine outcomes in depressed patients deteriorated to a greater degree after treatment than did cocaine outcomes in patients without depression, particularly in patients in RP who had a current depressive disorder at baseline. The best alcohol outcomes were obtained in nondepressed patients who received RP. The results suggest that extended continuing care treatment may be warranted for cocaine-dependent patients with co-occurring depressive disorders. C1 Univ Penn, Treatment Res Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP McKay, JR (reprint author), Univ Penn, Treatment Res Ctr, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [K02 DA00361, R01 DA10262, P50 DA05186] NR 59 TC 63 Z9 63 U1 1 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 2002 VL 16 IS 3 BP 225 EP 235 DI 10.1037//0893-164X.16.3.225 PG 11 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 592AC UT WOS:000177913700006 PM 12236457 ER PT J AU Alterman, AI Gariti, P Niedbala, RS AF Alterman, AI Gariti, P Niedbala, RS TI Varying results for immunoassay screening kits for cotinine level SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article ID SMOKING AB Our earlier study found that although enzyme-linked immunosorbent analysis (ELISA) screening assays for urine cotinine indicated use in former smoking treatment patients who reported abstinence, this finding was sometimes incorrect when validated against gas chromatography/mass spectrometry (GC/MS; P. Gariti, A. I. Alterman, R. Ehrmann, F. D. Mulvaney, & C. P, O'Brien, 2002). In the current validation study, separate urine samples of 71 of these same patients were reanalyzed by an independent laboratory in blinded fashion using a screening enzyme immunoassay (EIA) analysis and GC/MS confirmation. EIA results showed almost total agreement with confirmatory testing. The findings indicate that use of screening ELISA/EIA for urine cotinine can detect unreported cases of smoking in former patients, but that care is needed in selecting a laboratory for conducting these tests. C1 Univ Penn, Sch Med, Treatment Res Ctr, Philadelphia, PA 19104 USA. OraSure Technol Inc, Bethlehem, PA USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Alterman, AI (reprint author), Univ Penn, Sch Med, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA 10070] NR 9 TC 5 Z9 6 U1 1 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 2002 VL 16 IS 3 BP 256 EP 259 DI 10.1037//0893-164X.16.3.256 PG 4 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 592AC UT WOS:000177913700010 PM 12236461 ER PT J AU Hitsman, B Abrams, DB Shadel, WG Niaura, R Borrelli, B Emmons, KM Brown, RA Swift, RM Monti, PM Rohsenow, DJ Colby, SM AF Hitsman, B Abrams, DB Shadel, WG Niaura, R Borrelli, B Emmons, KM Brown, RA Swift, RM Monti, PM Rohsenow, DJ Colby, SM TI Depressive symptoms and readiness to quit smoking among cigarette smokers in outpatient alcohol treatment SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article; Proceedings Paper CT 7th Annual Meeting of the Society-for-Research-on-Nicotine-and-Tabacco CY MAR 23-25, 2001 CL SEATTLE, WASHINGTON SP Soc Res Nicotine Tobacco ID CONTEMPLATION LADDER; NICOTINE DEPENDENCE; TOBACCO SMOKING; CESSATION AB The authors examined whether length of alcohol abstinence and depressive symptoms were related to motivational readiness to consider smoking cessation among patients in alcohol treatment. Participants were adults (N = 253) enrolled in a smoking cessation trial. Controlling for gender, depressive symptoms, and nicotine dependence, hierarchical regression analysis of readiness scores revealed a significant interaction of days since last drink and depressive symptoms. It was found that a greater number of days since last drink was associated with greater readiness, but only among patients with low scores on the Center for Epidemiologic Studies Depression Scale (L. S. Radloff. 1977). The findings suggest that alcoholic smokers with low depressive symptoms are more receptive to quitting smoking after sustained alcohol abstinence. C1 Miriam Hosp, Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI 02903 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brown Med Sch, Ctr Alcohol & Addict Studies, Providence, RI USA. Vet Affairs Med Ctr, Providence, RI USA. RP Abrams, DB (reprint author), Miriam Hosp, Brown Med Sch, Ctr Behav & Prevent Med, CORO Bldg,Suite 5000,1 Hoppin St, Providence, RI 02903 USA. FU NCI NIH HHS [P50 CA84719]; NIAAA NIH HHS [R01 AA11211]; NIDA NIH HHS [F31 DA05854] NR 25 TC 16 Z9 17 U1 1 U2 8 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 2002 VL 16 IS 3 BP 264 EP 268 DI 10.1037//0893-164X.16.3.264 PG 5 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 592AC UT WOS:000177913700012 PM 12236463 ER PT J AU Koelsch, S Schmidt, BH Kansok, J AF Koelsch, S Schmidt, BH Kansok, J TI Effects of musical expertise on the early right anterior negativity: An event-related brain potential study SO PSYCHOPHYSIOLOGY LA English DT Article ID ELECTROPHYSIOLOGICAL EVIDENCE; MUSICIANS; REPRESENTATION; EXPECTANCY; ERP; ORGANIZATION; PLASTICITY; RESPONSES; CONTEXTS; LANGUAGE AB Event-related brain potentials in response to harmonically inappropriate chords were compared for musical experts and novices. Similar to previous studies, these chords elicited an early right anterior negativity (ERAN). The amplitude of the ERAN was clearly larger for musical experts than for novices, presumably because experts had more specific musical expectancies than novices. Chords with a physically deviant timbre elicited a mismatch negativity that did not differentiate the groups, indicating that the larger ERAN in experts was not due to a general enhanced auditory sensitivity. The ERAN reflects fast and automatic neural mechanisms that process complex musical (music-syntactic) irregularities, and the present results indicate that these mechanisms can be modulated by expertise. C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02245 USA. Max Planck Inst Cognit Neurosci, Leipzig, Germany. Inst Gen Psychol, Leipzig, Germany. RP Harvard Univ, Sch Med, BIDMC, Dana 779,330 Brookline Ave, Boston, MA 02245 USA. EM mail@stefan-koelsch.de NR 39 TC 109 Z9 111 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2002 VL 39 IS 5 BP 657 EP 663 DI 10.1017/S0048577202010508 PG 7 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LN UT WOS:000177939300014 PM 12236333 ER PT J AU Surman, OS Cosimi, AB Fukunishi, I Kawaii, T Findley, J Kita, Y Makuuchi, M AF Surman, OS Cosimi, AB Fukunishi, I Kawaii, T Findley, J Kita, Y Makuuchi, M TI Some ethical and psychiatric aspects of right-lobe liver transplantation in the United States and Japan SO PSYCHOSOMATICS LA English DT Review ID ORGAN-TRANSPLANTATION; BRAIN-DEATH; DONOR; CANDIDATES; ALLOCATION; DONATION AB Cadaver sources are insufficient for the increasing demand for liver transplantation. Right-lobe liver transplantation from living donors is fully developed in Japan and has been rapidly increasing in the United States during the past 2 years, although donor risk is greater than in other types of solid organ transplantation. The authors examine the psychiatric and ethical aspects of right-lobe liver transplantation in light of cultural differences between the United States and Japan. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. Tokyo Inst Psychiat, Tokyo, Japan. Tokyo Univ Hosp, Dept Surg, Tokyo 113, Japan. RP Surman, OS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 815,15 Parkman St, Boston, MA 02114 USA. RI 幕内, 雅敏/A-2140-2012 NR 45 TC 13 Z9 13 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 SEP-OCT PY 2002 VL 43 IS 5 BP 347 EP 353 DI 10.1176/appi.psy.43.5.347 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 596VX UT WOS:000178188100001 PM 12297602 ER PT J AU Otto, MW Nierenberg, AA AF Otto, MW Nierenberg, AA TI Assay sensitivity, failed clinical trials, and the conduct of science SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Editorial Material ID PANIC DISORDER; METHODOLOGICAL CONTROVERSIES C1 Massachusetts Gen Hosp, Cognit Behav Therapy Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Cognit Behav Therapy Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 11 TC 33 Z9 33 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD SEP-OCT PY 2002 VL 71 IS 5 BP 241 EP 243 DI 10.1159/000064813 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 591YN UT WOS:000177908000001 PM 12207103 ER PT J AU Mataix-Cols, D Marks, IM Greist, JH Kobak, KA Baer, L AF Mataix-Cols, D Marks, IM Greist, JH Kobak, KA Baer, L TI Obsessive-compulsive symptom dimensions as predictors of compliance with and response to behaviour therapy: Results from a controlled trial SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE obsessive-compulsive disorder; symptom dimensions; behaviour therapy; exposure and ritual prevention; outcome predictors ID DISORDER; PERSONALITY; SUBTYPES; EXPOSURE; SCALE; OCD AB Background. Recent factor-analytic studies in obsessive-compulsive disorder (OCD) identified consistent symptom dimensions. Support for the validity of these dimensions. comes from studies of psychiatric comorbidity, functional, brain imaging, genetic transmission, and treatment response to medications. This study examined whether previously identified OCD symptom dimensions are associated with treatment compliance and response to behaviour therapy (BT) for OCD. Methods: One hundred and fifty-three OCD outpatients who participated in a multi-centre randomised controlled trial of computer-versus clinician-guided BT for OCD were included in the study. Logistic and multiple regression models tested for significant predictors of compliance with and response to BT and relaxation. Results: The patients studied were phenomenologically comparable (including the presence of 'pure' obsessions and mental rituals) to those in previous serotonin reuptake inhibitor (SRI) trials and those in clinical epidemiology studies. High scorers on the 'hoarding' dimension were more likely to drop out prematurely from the study and tended to improve less. For those completing treatment, the strongest predictor of outcome was pre-treatment severity. Initial depression scores were unrelated to outcome. After controlling for symptom severity, higher scores on the 'sexual/religious obsessions' factor predicted poorer outcome with BT, especially when computer-guided. Conclusions: BT is especially indicated for OCD patients With aggressive/checking, contamination/cleaning and symmetry/ordering symptoms. Previous accounts of unsuccessful BT in patients with hoarding symptoms may be due in, part to their propensity to drop out earlier from treatment. Patients with sexual/religious obsessions, but not those with mental rituals, might respond less well to traditional BT techniques. Existing treatments need to be refined and/or new treatments developed to improve these patients' adherence and response to treatment. Copyright (C) 2002 S. Karger AG, Basel. C1 Guys Hosp, GKT Sch Med, Div Psychol Med, London SE1 9RT, England. Guys Hosp, Inst Psychiat, London SE1 9RT, England. Imperial Coll Sch Med, Dept Psychiat, London, England. Healthcare Technol Syst, Madison, WI USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Mataix-Cols, D (reprint author), Guys Hosp, GKT Sch Med, Div Psychol Med, 5th Floor,Thomas Guy House, London SE1 9RT, England. RI Mataix-Cols, David/G-3843-2010 OI Mataix-Cols, David/0000-0002-4545-0924 NR 39 TC 232 Z9 237 U1 1 U2 20 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD SEP-OCT PY 2002 VL 71 IS 5 BP 255 EP 262 DI 10.1159/000064812 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 591YN UT WOS:000177908000003 PM 12207105 ER PT J AU Petersen, T Hughes, M Papakostas, GI Kant, A Fava, M Rosenbaum, JF Nierenberg, AA AF Petersen, T Hughes, M Papakostas, GI Kant, A Fava, M Rosenbaum, JF Nierenberg, AA TI Treatment-resistant depression and axis II comorbidity SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA German DT Article DE axis II comorbidity; treatment-resistant depression; predictors of response; personality ID PERSONALITY-DISORDERS; MAJOR DEPRESSION; UNIPOLAR DEPRESSION; ALEXITHYMIA; PREDICTORS AB Background. Researchers of unipolar depression have speculated that personality disturbance is a contributing factor in the development of treatment resistance. The purpose of this study was to compare the prevalence of Axis II disorders between a sample of rigorously defined, treatment-resistant depressed outpatients and a sample of depressed outpatients not having experienced treatment resistance. Methods: 53 patients with treatment-resistant depression (TRD) and 105 patients with non-treatment-resistant depression (non-TRD) were recruited through respective outpatient clinical trials at the Massachusetts General Hospital's Depression Clinical and Research Program. Diagnosis of Major Depressive Disorder was made using the Structured Clinical Interview for the DSM-III-R, personality disorders were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders, and antidepressant treatment resistance was defined using the McLean Hospital Antidepressant Treatment Record. Participants from both studies were matched for baseline HAM-D-17 total score and gender. Multiple chi-square analysis was used to compare frequencies of Axis II disorders between TRD and non-TRD patients as well as to compare categorical baseline demographic variables. Unpaired t tests were used to compare baseline demographic and clinical variables measured in a continuous manner. Results: Non-TRD patients had a higher rate of obsessive-compulsive personality disorder than TRD patients, but this difference was not statistically significant after adjusting for multiple comparisons. No other differences were found to be statistically significant. Range of Axis II comorbidity was 0.0-30.2% for TRD patients and 2.9-37.1% for non-TRD patients. Conclusions: In this sample, treatment resistance in a current major depressive episode was not associated with an increased rate of Axis II disorders. Strengths of this study include the use of structured interview instruments to assess Axis I and II conditions, and having the two study groups matched for gender and baseline severity of depression. Limitations of this study include a modest sample size and reliance on DSM personality constructs. Copyright (C) 2002 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Petersen, T (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 19 TC 22 Z9 23 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD SEP-OCT PY 2002 VL 71 IS 5 BP 269 EP 274 DI 10.1159/000064808 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 591YN UT WOS:000177908000005 PM 12207107 ER PT J AU Chen, NH Li, HY Gliklich, RE Chu, CC Liang, SC Wang, PC AF Chen, NH Li, HY Gliklich, RE Chu, CC Liang, SC Wang, PC TI Validation assessment of the Chinese version of the Snore Outcomes Survey SO QUALITY OF LIFE RESEARCH LA English DT Article DE validation; Chinese version SOS ID OBSTRUCTIVE SLEEP-APNEA; HEALTH SURVEY SF-36; REDUCTION; SURGERY AB The aim of this study was to use a parallel model to translate the Snore Outcomes Survey (SOS) into Mandarin Chinese language by comparing performing characteristics and statistical properties of the original and Chinese versions SOS. The Chinese version SOS (CSOS) was validated in a prospective, non-randomized manner. A total of 359 patients with sleep-disordered breathing (SDB) aged 18 years and older diagnosed as having SDB participated in the study at entry. Reliability, validity, and longitudinal sensitivity data for CSOS were obtained. CSOS demonstrated good test-retest reliability (Intra-class correlation coefficient = 0.751). The Cronbach's alpha coefficient was 0.86. The item-total correlation coefficients varied from 0.30 to 0.99. The CSOS correlated well with polysomnogram (PSG) parameters including respiratory distress index (RDI), lowest arterial O-2 saturation (LAST). CSOS also yielded significant correlations with vitality subscale of Chinese Taiwan version SF-36 (r = 0.4, p = 0.0011). The standard response mean (SRM) for CSOS was 1.33. The validation demonstrated only minor effects of language; the statistical properties of the CSOS were equivalent to the English version. The CSOS is a valid tool to evaluate adults with SDB among Chinese-speaking population. C1 Chang Gung Mem Hosp, Sleep Ctr, Dept Pulm & Crit Care Med, Taipei 10591, Taiwan. Chang Gung Mem Hosp, Dept Otolaryngol, Taipei 10591, Taiwan. Chang Gung Univ, Taipei, Taiwan. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Clin Outcomes Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Dept Hlth, Taipei, Taiwan. China Med Coll, Dept Publ Hlth, Taichung, Taiwan. Cathay Gen Hosp, Dept Otolaryngol, Taipei 106, Taiwan. RP Wang, PC (reprint author), Cathay Gen Hosp, Dept Otolaryngol, 280,Sec 4,Jen Ai Rd, Taipei 106, Taiwan. NR 20 TC 17 Z9 17 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD SEP PY 2002 VL 11 IS 6 BP 601 EP 607 DI 10.1023/A:1016337008763 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 573FL UT WOS:000176818600011 PM 12206581 ER PT J AU Wittenberg, J Harisinghani, MG Jhaveri, K Varghese, J Mueller, PR AF Wittenberg, J Harisinghani, MG Jhaveri, K Varghese, J Mueller, PR TI Algorithmic approach to CT diagnosis of the abnormal bowel wall SO RADIOGRAPHICS LA English DT Article DE computed tomography (CT), tissue characterization; intestines, CT ID COMPUTED-TOMOGRAPHY; CROHNS-DISEASE; SPIRAL CT; ISCHEMIA; COLITIS; SIGN; HEMORRHAGE; MANAGEMENT; FEATURES; CANCER AB Computed tomography demonstrates intestinal wall abnormalities that can be analyzed by categorizing attenuation changes in the intestinal wall and transposing morphologic characteristics learned from barium studies. These attenuation patterns include white, gray, water halo sign, fat halo sign, and black. The white pattern represents avid contrast material enhancement that uniformly affects most of the thickened bowel wall. If the bowel wall is enhanced to a degree equal to or greater than that of venous opacification in the same scan, it should be classified in the white attenuation pattern. Common diagnoses with this pattern include idiopathic inflammatory bowel diseases and vascular disorders. The gray pattern is defined as a thickened bowel wall with limited enhancement whose homogeneous attenuation is comparable with that of enhanced muscle. This pattern is used to differentiate between benign and malignant disease, but it is the least specific of the patterns and should be combined with morphologic observations. The water halo sign indicates stratification within a thickened bowel wall that consists of either two or three continuous, symmetrically thickened layers. Common diagnoses with this sign include idiopathic inflammatory bowel diseases, vascular disorders, infectious diseases, and radiation damage. The fat halo sign refers to a three-layered target sign of thickened bowel in which the middle or "submucosal" layer has a fatty attenuation. Common diagnoses with this sign include Crohn disease in the small intestine and idiopathic inflammatory bowel diseases in the colon. Black attenuation is the equivalent of pneumatosis, and this pattern is commonly seen in ischemia, infection, and trauma. (C)RSNA, 2002. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Wittenberg, J (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. NR 24 TC 60 Z9 61 U1 0 U2 5 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 SEP-OCT PY 2002 VL 22 IS 5 BP 1093 EP 1107 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592VP UT WOS:000177957800011 PM 12235339 ER PT J AU Wittenberg, J AF Wittenberg, J TI Algorithmic approach to CT diagnosis of the abnormal bowel wall - Author's response SO RADIOGRAPHICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Wittenberg, J (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 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 SEP-OCT PY 2002 VL 22 IS 5 BP 1108 EP 1109 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592VP UT WOS:000177957800013 ER PT J AU Romero, JM Lev, MH Chan, ST Connelly, MM Curiel, RC Jackson, AE Gonzalez, RG Ackerman, RH AF Romero, JM Lev, MH Chan, ST Connelly, MM Curiel, RC Jackson, AE Gonzalez, RG Ackerman, RH TI US of neurovascular occlusive disease: Interpretive pearls and pitfalls SO RADIOGRAPHICS LA English DT Article DE carotid arteries, stenosis or obstruction; carotid arteries, US; subclavian steal syndrome; ultrasound (US), Doppler studies; vertebral arteries, US ID CAROTID-ARTERY STENOSIS; DOPPLER ULTRASOUND CRITERIA; ENDARTERECTOMY SPECIMENS; PSEUDO-OCCLUSION; FLOW AB Ultrasonography (US) of the head and neck is a convenient but operator-dependent screening tool for detection and diagnosis of neurovascular occlusive disease. In US examination of the extracranial carotid arteries, stenosis is most commonly graded according to the peak systolic Doppler velocity in the region of maximal luminal narrowing rather than according to the percentage of atheromatous plaque occupying the lumen. However, the peak systolic velocity is not always reliable in estimation of the degree of stenosis. General diagnostic pitfalls include technical difficulties with scanning, failure to review the spectral waveform patterns, the presence of additional stenotic lesions, and anatomic variants. Specific examples of pitfalls include tandem lesions, differentiation of pseudo-occlusion from true total occlusion, pseudo-normalization of velocities in cases of very severe stenosis, lesions of the carotid artery origin or aortic valve, progression of subclavian steal, underestimation of severe stenosis due to heavily calcified plaque, a persistent trigeminal artery, and contralateral carotid artery stenosis. Although conventional angiography remains the standard of reference for assessment of carotid artery disease recognition of these common, sources of error in US can improve the accuracy of this noninvasive test in diagnosis of carotid artery occlusion. (C)RSNA, 2002. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hong Kong Polytech Univ, Dept Optometry & Radiog, Kowloon, Hong Kong, Peoples R China. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. RI Chan, Suk-tak/G-5846-2015 NR 14 TC 9 Z9 9 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2002 VL 22 IS 5 BP 1165 EP 1176 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592VP UT WOS:000177957800019 PM 12235345 ER PT J AU Tong, SC Pitman, M Anupindi, SA AF Tong, SC Pitman, M Anupindi, SA TI Best cases from the AFIP - Ileocecal enteric duplication cyst: Radiologic-pathologic correlation SO RADIOGRAPHICS LA English DT Article DE intestines, abnormalities; intestines, cysts ID ILEAL C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Anupindi, SA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 34 Fruit St,White 246, Boston, MA 02114 USA. NR 13 TC 9 Z9 13 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2002 VL 22 IS 5 BP 1217 EP 1222 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592VP UT WOS:000177957800022 PM 12235349 ER PT J AU Steinbach, LS Palmer, WE Schweitzer, ME AF Steinbach, LS Palmer, WE Schweitzer, ME TI Special focus session - MR arthrography SO RADIOGRAPHICS LA English DT Article DE ankle, arthrography; arthrography, contrast media; elbow, arthrography; hip, arthrography; joints, MR; knee, arthrography; magnetic resonance (MR), arthrography; shoulder, arthrography; wrist, arthrography ID ULNAR COLLATERAL LIGAMENT; ANTERIOR SHOULDER INSTABILITY; ACETABULAR LABRAL TEARS; CHRONIC WRIST PAIN; TRIANGULAR FIBROCARTILAGE; GLENOHUMERAL JOINT; ROTATOR CUFF; HISTOLOGIC CORRELATION; ANKLE INSTABILITY; CONTRAST MATERIAL AB Direct magnetic resonance (MR) arthrography with injection of saline solution or diluted gadolinium can be useful for evaluating certain pathologic conditions in the joints. It is most helpful for outlining labral-ligamentous abnormalities in the shoulder and distinguishing partial-thickness from full-thickness tears in the rotator cuff, demonstrating labral tears in the hip, showing partial- and full-thickness tears of the collateral ligament of the elbow and delineating bands in the elbow, identifying residual or recurrent tears in the knee following meniscectomy, increasing the certainty of perforations of the ligaments and triangular fibrocartilage in the wrist, correctly identifying ligament tears in the ankle and increasing the sensitivity for ankle impingement syndromes, assessing the stability of osteochondral lesions in the articular surface of joints, and delineating loose bodies in joints. Indirect MR arthrography with intravenous administration of diluted gadolinium may be performed when direct arthrography is inconvenient or not logistically feasible. Although indirect MR arthrography has some disadvantages vis-A-vis direct MR arthrography, it does not require fluoroscopic guidance or joint injection and it is superior to conventional MR imaging in delineating structures when there is minimal joint fluid. In addition, vascularized or inflamed tissue will enhance with this method. Indirect MR arthrography can be used to rule in or diagnose abnormalities and to exclude abnormalities. (C)RSNA, 2002. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA. RP Steinbach, LS (reprint author), Univ Calif San Francisco, Dept Radiol, 505 Parnassus Ave,Suite M392, San Francisco, CA 94143 USA. NR 70 TC 144 Z9 149 U1 1 U2 2 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 SEP-OCT PY 2002 VL 22 IS 5 BP 1223 EP 1246 PG 24 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592VP UT WOS:000177957800023 PM 12235350 ER PT J AU Adriaensen, MEAPM Bosch, JL Halpern, EF Hunink, MGM Gazelle, GS AF Adriaensen, MEAPM Bosch, JL Halpern, EF Hunink, MGM Gazelle, GS TI Elective endovascular versus open surgical repair of abdominal aortic aneurysms: Systematic review of short-term results SO RADIOLOGY LA English DT Article; Proceedings Paper CT 87th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 25-30, 2001 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE aneurysm, abdominal; aneurysm, aortic; aneurysm, surgery; data, analysis; grafts, interventional procedures ID STENT-GRAFT; REPORTING STANDARDS; CLINICAL-TRIALS; AAA TREATMENT; MULTICENTER; COST; EXPERIENCE; COMPLICATIONS; ENDOLEAKS AB Purpose: To summarize and compare published short-term results of elective endovascular and open surgical repair of abdominal aortic aneurysms. Materials and Methods: A MEDLINE search of the English literature was performed. Studies with at least 10 patients in each treatment group were included if they reported patient characteristics, complications, and mortality. Two reviewers independently extracted the data. A random-effects model was used to pool the data and calculate pooled odds ratios (endovascular vs open surgical repair). Results: Nine studies were included, reported results of 1.318 procedures (687 endovascular repair and 631 open surgical repair). Mean blood loss was 456 mL for endovascular repair and 1,202 mL for open surgical repair (P=.003). On average, patients undergoing endovascular repair spent 0.5 days in the intensive care unit and 3.9 days in the hospital, and patients undergoing open surgical repair spent 2.2 days (P=.04) in the intensive care unit and 10.3 days (P=.02) in the hospital. The pooled 30-day-mortality was 0.03 for endovascular repair (95% CI: 0.02, 0.04) and 0.04 for open surgical repair (95% CI: 0.00, 0.07) (P=.03), and the odds ratio was 0.55 (95% CI: 0.33, 0.92). The pooled local and/or vascular complication rate was 0.16 for endovascular repair (95% CI: 0.06, 0.25) and 0.12 for open surgical repair (95% CI: 0.06, 0.18)(P=.46), and the odds ratio was 0.97 (95% CI: 0.62, 1.54). The pooled systemic and/or remote complication rate was 0.17 for endovascular repair (95% CI: 0.09, 0.25) and 0.44 for open surgical repair (95% CI: 0.21, 0.66) (P<.001), and the odds ratio was 0.22 (95% CI: 0.11, 0.45). Conclusion: On the basis of this systematic review, endovascular repair results in less blood loss, shorter intensive care unit and hospital stays, lower 30-day mortality, and lower systemic and/or remote complication rates than those of open surgical repair. (C) RSNA, 2002. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Gazelle, GS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 0 Emerson Pl,Ste 2H, Boston, MA 02114 USA. NR 40 TC 75 Z9 77 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 SEP PY 2002 VL 224 IS 3 BP 739 EP 747 DI 10.1148/radiol.2243011675 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 587BY UT WOS:000177621700018 PM 12202708 ER PT J AU Monsky, WL Kruskal, JB Lukyanov, AN Girnun, GD Ahmed, M Gazelle, GS Huertas, JC Stuart, KE Torchilin, VP Goldberg, SN AF Monsky, WL Kruskal, JB Lukyanov, AN Girnun, GD Ahmed, M Gazelle, GS Huertas, JC Stuart, KE Torchilin, VP Goldberg, SN TI Radio-frequency ablation increases intratumoral liposomal doxorubicin accumulation in a rat breast tumor model SO RADIOLOGY LA English DT Article DE animals; chemotherapy; hyperthermia; liposomes; neoplasms; radiofrequency (RF) ablation ID RADIOFREQUENCY THERMAL ABLATION; TISSUE ABLATION; HEPATOCELLULAR-CARCINOMA; LIVER METASTASES; HEPATIC METASTASES; HYPERTHERMIA; ELECTRODE; COAGULATION; MACROMOLECULES; TEMPERATURE AB PURPOSE: To determine whether intratumoral accumulation of liposomal doxorubicin or free unencapsulated doxorubicin is increased when combined with radio-frequency (RF) ablation. MATERIALS AND METHODS: Two 1.2-1.5-cm R3230 mammary adenocarcinomas were grown within the mammary fat pads of 19 female Fischer rats. One tumor of each pair was treated with RF ablation (tip temperature, 70degreesC +/- 2 [SD]; 120 mA +/- 75) for 5 minutes, whereas the other tumor was a control. Intravenous liposomal doxorubicin (1 mg in 500 muL, n = 6) or intravenous free unencapsulated doxorubicin (n = 7) was administered immediately following RF ablation. Doxorubicin was extracted in acid alcohol from tumors 24 hours following RF ablation, and fluorescent spectrophotometry was used to quantify extracted doxorubicin. Comparisons of intratumoral doxorubicin accumulation in tumors treated with RF ablation and in untreated tumors were analyzed with parametric (paired Student t test) and nonparametric (Wilcoxon rank sum test) statistics. Findings at autoradiography with densitometry (six additional tumors) demonstrated the spatial distribution of the intratumoral accumulation of liposomal doxorubicin. RESULTS: When RF ablation preceded administration of liposomal doxorubicin, mean intratumoral doxorubicin concentration was 5.6 mug/g +/- 2.1 (range, 1.9-7.7 mug/g), whereas 1.0 mug/g +/- 0.4 (range, 0.5-1.5 mug/g) was present in control tumors not treated with RF ablation (P < .05). Thus, there was a mean 7.1-fold +/- 4.9 increase in intratumoral doxorubicin accumulation following RF ablation (range, 2.1-14.5-fold) compared with the amount without RF pretreatment (P < .05). Increased intratumoral accumulation was not seen in animals receiving free doxorubicin with (mean, 0.4 mug/g +/- 0.1) or without (mean, 0.8 mug/g +/- 0.4) RF pretreatment (P = .07). Autoradiographic findings demonstrated accumulation of liposomal doxorubicin in a peripheral rim of tumor adjacent to the zone of coagulation. CONCLUSION: RF ablation augments the delivery of systemic antineoplastic agents such as liposomal doxorubicin. (C) RSNA, 2002. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. Northeastern Univ, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Goldberg, SN (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. NR 42 TC 52 Z9 53 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 SEP PY 2002 VL 224 IS 3 BP 823 EP 829 DI 10.1148/radiol.2243011421 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 587BY UT WOS:000177621700031 PM 12202721 ER PT J AU Stone, ME AF Stone, ME TI Homosexuality and science: A guide to debates. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Reference Serv, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Reference Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD FAL PY 2002 VL 42 IS 1 BP 84 EP 85 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 604TC UT WOS:000178636300023 ER PT J AU Rehman, SU Cope, DW Basile, JN AF Rehman, SU Cope, DW Basile, JN TI Metastatic gastroesophageal adenocarcinoma to skeletal muscle: A unique event SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID CARCINOMA; CANCER; INFILTRATION; THIGH; COLON; TUMOR AB Skeletal muscle is rarely the site of metastatic cancer, though a few such cases have been reported. Esophageal adenocarcinoma metastasic to skeletal muscle has not previously been reported in the literature. We describe the case of 71-year-old African American male with stage IV adenocarcinoma of die gastroesophageal junction. He had severe and disabling pain in the right thigh, which was tender to palpation. The pain was unresponsive to nonsteroidal anti-inflammatory drugs and full-close narcotics. Plain x-ray films and bone scan were nondiagnostic. Magnetic resonance imaging showed a soft tissue mass involving the thigh muscles, anterior and medial to the right femur. Computed tomography (CT)-guided biopsy revealed that the thigh mass was metastatic adenocarcinoma consistent with the primary gastroesophageal cancer. Metastasis to muscle is rare, but physicians should be aware of the possibility because detection requires specific tests. We discuss the role of these tests, as well as available treatment options. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Rehman, SU (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA. NR 35 TC 12 Z9 12 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD SEP PY 2002 VL 95 IS 9 BP 1076 EP 1078 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 596KR UT WOS:000178164500031 PM 12356116 ER PT J AU Briggs, SM Schnitzer, JJ AF Briggs, SM Schnitzer, JJ TI The World Trade Center terrorist attack: Changing priorities for surgeons in disaster response SO SURGERY LA English DT Article ID THREAT RP Briggs, SM (reprint author), Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, 8 Hawthorne Pl,Suite 114, Boston, MA 02114 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2002 VL 132 IS 3 BP 506 EP 512 DI 10.1067/msy.2002.127981 PG 7 WC Surgery SC Surgery GA 600EZ UT WOS:000178378800013 PM 12324766 ER PT J AU Sarr, MG Warshaw, AL AF Sarr, MG Warshaw, AL TI Responsibility of authorship SO SURGERY LA English DT Editorial Material C1 Mayo Clin & Mayo Fdn, Gastroenterol Res Unit, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sarr, MG (reprint author), Mayo Clin & Mayo Fdn, Gastroenterol Res Unit, Alfred 2-435,200 1st St SW, Rochester, MN 55905 USA. NR 2 TC 0 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2002 VL 132 IS 3 BP 521 EP 521 DI 10.1067/msy.2002.126507 PG 1 WC Surgery SC Surgery GA 600EZ UT WOS:000178378800016 PM 12324769 ER PT J AU Chaum, E Hatton, MP AF Chaum, E Hatton, MP TI Gene therapy for genetic and acquired retinal diseases SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE apoptosis; gene therapy; growth factors; proliferative vitreoretinopathy; retinal pigment epithelium retina; retinal degeneration; retinitis pigmentosa; retinoblastoma; ribozymes; transfection; viruses ID PIGMENT EPITHELIAL-CELLS; FIBROBLAST-GROWTH-FACTOR; CILIARY NEUROTROPHIC FACTOR; HERPES-SIMPLEX VIRUS; RECOMBINANT ADENOASSOCIATED VIRUS; DOMINANT RETINITIS-PIGMENTOSA; ORNITHINE-DELTA-AMINOTRANSFERASE; RETROVIRUS-MEDIATED TRANSFER; EXPERIMENTAL PROLIFERATIVE VITREORETINOPATHY; RECONSTITUTED RETINOBLASTOMA CELLS AB We present an overview of the current status of basic science and translational research being applied to gene therapy for eye disease, focusing on diseases of the retina. We discuss the viral and nonviral methods being used to transfer genes to the retina and retinal pigment epithelium, and the advantages and disadvantages of each approach. We review the various genetic and somatic treatment strategies that are being used for genetically determined and acquired diseases of the retina, including gene replacement, gene silencing by ribozymes and antisense oligonucleotides, suicide gene therapy, antiapoptosis, and growth factor therapies. The rationales for the specific therapeutic approaches to each disease are discussed. Schematics of gene transfer methods and therapeutic approaches are presented together with a glossary of gene transfer terminology. (C) 2002 by Elsevier Science Inc. All rights reserved. C1 Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Chaum, E (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, 956 Court Ave,Rm D228, Memphis, TN 38163 USA. NR 231 TC 17 Z9 20 U1 1 U2 3 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 SEP-OCT PY 2002 VL 47 IS 5 BP 449 EP 469 AR PII S0039-6257(02)00336-3 DI 10.1016/S0039-6257(02)00336-3 PG 21 WC Ophthalmology SC Ophthalmology GA 606HA UT WOS:000178727500003 PM 12431694 ER PT J AU Bokhari, A Connolly, S Coull, BA Harvey, EA Holmes, LB AF Bokhari, A Connolly, S Coull, BA Harvey, EA Holmes, LB TI Effects on toes from prenatal exposure to anticonvulsants SO TERATOLOGY LA English DT Article ID FETAL-HYDANTOIN SYNDROME; TERATOGENICITY; DRUGS; INHIBITION AB Background: Changes in the distal phalanges of the fingers, including coned epiphyses and hypoplasia of the phalanges, are recognized teratogenic effects of the anticonvulsant drugs phenytoin and phenobarbital We hypothesized that the frequency of these changes would also be increased in the toes of children exposed to these drugs in comparison to unexposed children, Methods: We report on the findings in an analysis of radiographs of the feet of 63 children exposed in utero to either phenytoin alone, phenobarbital alone or both drugs and 56 unexposed comparison children. Results: Only subtle changes were identified. The frequency of coned epiphyses and hypoplasia of phalanges of the toes was the same in both the anticonvulsant and unexposed children. Among the anticonvulsant-exposed children, however, there was a strong association between the presence of coned epiphyses in the feet and in the hands: all five children with coned epiphyses in the hands, as described previously in the same individuals by Lu et al. ([20001 Teratology 61: 277-283) had coned epiphyses in their feet (P = 0.0012). Measurements showed a shortening of metatarsals in all three treatment groups, but this was significant only in the phenytoin monotherapy-exposed children. Conclusions: Subtle changes are present in the phalanges and metatarsals of the feet of anticonvulsant-exposed children, but the overall frequency is much less than occurred in the hands of the same children We conclude that the presence of either coned epiphyses or hypoplasia of the phalanges of the toes cannot be considered a distinctive feature of the teratogenicity of the anticonvulsant drugs phenytoin and phenobarbital. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Warren 801,55 Fruit St, Boston, MA 02114 USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD SEP PY 2002 VL 66 IS 3 BP 122 EP 126 DI 10.1002/tera.10085 PG 5 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 589CX UT WOS:000177741400005 PM 12210473 ER PT J AU Zubair, AC Zahrein, D Neuberg, D Gribben, J Freedman, A Ritz, J AF Zubair, AC Zahrein, D Neuberg, D Gribben, J Freedman, A Ritz, J TI Early neutrophil engraftment provides a functional assessment of long-term hematopoietic reconstitution following autologous bone marrow transplant. SO TRANSFUSION LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 26-29, 2002 CL ORLANDO, FLORIDA SP Amer Assoc Blood Banks C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2002 VL 42 IS 9 SU S BP 7S EP 7S PG 1 WC Hematology SC Hematology GA 592MP UT WOS:000177941700024 ER PT J AU Dzik, WH Murphy, MF AF Dzik, WH Murphy, MF TI An international study of the performance of patient sample collection. SO TRANSFUSION LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 26-29, 2002 CL ORLANDO, FLORIDA SP Amer Assoc Blood Banks C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Blood Serv, Oxford, England. Int Soc Blood Transfus, BEST Working Party, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2002 VL 42 IS 9 SU S BP 26S EP 26S PG 1 WC Hematology SC Hematology GA 592MP UT WOS:000177941700093 ER PT J AU Purmal, A Serebryanik, I Kostka, S Cherry, P Kusinitz, F Gunderia, R Kratz, A Kuypers, F Rinder, C Rinder, H AF Purmal, A Serebryanik, I Kostka, S Cherry, P Kusinitz, F Gunderia, R Kratz, A Kuypers, F Rinder, C Rinder, H TI RBC morphology and physical properties of the RBC membrane are not affected by the INACTINE pathogen reduction process. SO TRANSFUSION LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 26-29, 2002 CL ORLANDO, FLORIDA SP Amer Assoc Blood Banks C1 VI Technol Inc, Watertown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Yale Univ, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2002 VL 42 IS 9 SU S BP 94S EP 94S PG 1 WC Hematology SC Hematology GA 592MP UT WOS:000177941700347 ER PT J AU Dzik, WH Anderson, JK O'Neill, EM Assmann, SF Kalish, LA Stowell, CP AF Dzik, WH Anderson, JK O'Neill, EM Assmann, SF Kalish, LA Stowell, CP TI A prospective, randomized clinical trial of universal WBC reduction SO TRANSFUSION LA English DT Article ID BLOOD-TRANSFUSION; LEUKOCYTE-DEPLETION; COLORECTAL-CANCER; ALLOGENEIC LEUKOCYTES; SURGERY; COMPONENTS; INFECTION; COMPLICATIONS; VALIDATION; RECURRENCE AB BACKGROUND: Recipient exposure to allogeneic donor WBCs results in transfusion complications for selected populations of recipients. Whether or not WBC reduction should be universally applied is highly controversial. STUDY DESIGN AND METHODS: In a general hospital, a randomized, controlled clinical trial of conversion to universal WBC reduction was conducted. Patients (11%) with established medical indications for WBC-reduced blood were not eligible. All other patients who required transfusion were assigned at random to receive either unmodified blood components or stored WBC-reduced RBCs and platelets. Analysis for each patient was restricted to the first hospitalization. RESULTS: All eligible patients (n = 2780) were enrolled. Three specified primary outcome measures were not different between the two groups: 1) in-hospital mortality (8.5% control; 9.0% WBC-reduced; OR, 0.94 [95% Cl, 0.72-1.22]; p = 0.64); 2) hospital length of stay (LOS) after transfusion (median number of days, 6.4 for control and 6.3 for WBC-reduced; p = 0.21); and 3) total hospital costs (median, $19,500 for control and $19,200 for WBC-reduced, p = 0.24). Secondary outcomes (intensive care LOS, postoperative LOS, antibiotic usage, and readmission rate) were not different between the two groups. Subgroup analysis based on patient age, sex, amount of blood transfused, or category of surgical procedure showed no effect of WBC reduction. Patients who received WBC-reduced blood had a lower incidence of febrile reactions (p = 0.06). CONCLUSION: A beneficial effect of conversion from selective to universal WBC reduction was not demonstrated. C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Baxter Healthcare Corp, Deerfield, IL 60015 USA. Unimed Pharmaceut, Deerfield, IL USA. Amer Red Cross, Blood Serv, New England Reg, Dedham, MA USA. New England Res Inst, Watertown, MA 02172 USA. RP Dzik, WH (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. NR 28 TC 88 Z9 91 U1 0 U2 3 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2002 VL 42 IS 9 BP 1114 EP 1122 DI 10.1046/j.1537-2995.2002.00182.x PG 9 WC Hematology SC Hematology GA 596XD UT WOS:000178191000004 PM 12430666 ER PT J AU Dzik, S Mincheff, M Puppo, F AF Dzik, S Mincheff, M Puppo, F TI Apoptosis, transforming growth factor-beta, and the immunosuppressive effect of transfusion SO TRANSFUSION LA English DT Article ID RED-CELLS; TGF-BETA; BLOOD; MACROPHAGES; LEUKOCYTES; STORAGE; SURGERY C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. George Washington Univ, Med Ctr, Dept Med, Tumor Immunol Lab, Washington, DC 20037 USA. Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. RP Dzik, S (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. NR 18 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2002 VL 42 IS 9 BP 1221 EP 1223 DI 10.1046/j.1537-2995.2002.00175.x PG 3 WC Hematology SC Hematology GA 596XD UT WOS:000178191000020 PM 12430682 ER PT J AU Allen, TM Kelleher, AD Zaunders, J Walker, BD AF Allen, TM Kelleher, AD Zaunders, J Walker, BD TI STI and beyond: the prospects of boosting anti-HIV immune responses SO TRENDS IN IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTE; ACTIVE ANTIRETROVIRAL THERAPY; TYPE-1 INFECTION; HIV-1-INFECTED PATIENTS; TREATMENT INTERRUPTION; CELL RESPONSES; VIRAL LOAD; DENDRITIC CELLS; PLASMA VIREMIA AB Twenty years into the HIV epidemic, highly active antiretroviral therapy (HAART) represents the only effective intervention to control HIV-1 disease progression. However, the prospect of life-long treatment with HAART is challenging given cumulative drug toxicities, difficulties with adherence to complicated regimens and the looming emergence of drug-resistant viruses. The challenges are even greater in resource-poor settings where costs and logistical problems with delivery represent formidable obstacles. Alternative approaches to long-term control of viral replication and disease progression are clearly needed. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. RP Allen, TM (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RI Zaunders, John/J-6553-2012; Allen, Todd/F-5473-2011 OI Zaunders, John/0000-0002-5912-5989; NR 63 TC 19 Z9 20 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD SEP PY 2002 VL 23 IS 9 BP 456 EP 460 AR PII S1471-4906(02)02297-4 DI 10.1016/S1471-4906(02)02297-4 PG 5 WC Immunology SC Immunology GA 589CJ UT WOS:000177740200006 PM 12200068 ER PT J AU Shipp, TD Mulliken, JB Bromley, B Benacerraf, B AF Shipp, TD Mulliken, JB Bromley, B Benacerraf, B TI Three-dimensional prenatal diagnosis of frontonasal malformation and unilateral cleft lip/palate SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE cleft lip/palate; prenatal diagnosis; three-dimensional ultrasound ID FACE SYNDROME; DYSPLASIA; HYPERTELORISM AB Frontonasal malformation includes a spectrum of anomalies involving the eyes, nose, lips, forehead and brain. We present a case in which a fetal labial cleft was initially identified using traditional two-dimensional sonography. Three-dimensional sonography with multiplanar reconstruction and surface-rendering were essential to establish the diagnosis of frontonasal malformation with severe nasal hypoplasia and unilateral complete cleft lip/palate. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Div Plast Surg, Boston, MA USA. RP Shipp, TD (reprint author), Diagnost Ultrasound Associates PC, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 13 TC 9 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD SEP PY 2002 VL 20 IS 3 BP 290 EP 293 DI 10.1046/j.1469-0705.2002.00773.x PG 4 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 593QE UT WOS:000178003000018 PM 12230455 ER PT J AU Carroll, PR Kantoff, PW Balk, SP Brown, MA D'Amico, AV George, DJ Grossfeld, GD Johnson, CS Kelly, WK Klotz, L Lee, WR Lubeck, DP McLeod, DG Oh, WK Pollack, A Sartor, O Smith, MR Hart, C AF Carroll, PR Kantoff, PW Balk, SP Brown, MA D'Amico, AV George, DJ Grossfeld, GD Johnson, CS Kelly, WK Klotz, L Lee, WR Lubeck, DP McLeod, DG Oh, WK Pollack, A Sartor, O Smith, MR Hart, C TI Newer approaches to androgen deprivation therapy in prostate cancer - Proceedings of the Second International Conference - Overview consensus statement SO UROLOGY LA English DT Editorial Material ID RADIATION-THERAPY; CARCINOMA C1 Univ Calif San Francisco, Med Ctr, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Toronto, ON, Canada. Wake Forest Univ, Sch Med, Dept Radiat Oncol, Winston Salem, NC 27109 USA. Walter Reed Army Med Ctr, Serv Urol, Washington, DC 20307 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Louisiana State Univ, Sch Med, Stanley Scott Canc Ctr, New Orleans, LA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. InforMEDical Inc, Narberth, PA USA. RP Carroll, PR (reprint author), Univ Calif San Francisco, Med Ctr, Sch Med, Dept Urol, U-575,533 Parnassus Ave, San Francisco, CA 94143 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 3 TC 27 Z9 27 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 SEP PY 2002 VL 60 IS 3A SU S BP 1 EP 6 AR PII S0090-4295(02)01559-5 DI 10.1016/S0090-4295(02)01559-5 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100001 PM 12231036 ER PT J AU Sartor, O Carroll, PR Pollack, A D'Amico, AV Kantoff, PW AF Sartor, O Carroll, PR Pollack, A D'Amico, AV Kantoff, PW TI Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer - Discussion SO UROLOGY LA English DT Editorial Material C1 Louisiana State Univ, New Orleans, LA 70112 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sartor, O (reprint author), Louisiana State Univ, New Orleans, LA 70112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 2002 VL 60 IS 3A SU S BP 11 EP 12 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100003 ER PT J AU Klotz, L McLeod, DG Kantoff, PW Carroll, PR D'Amico, AV Sartor, O AF Klotz, L McLeod, DG Kantoff, PW Carroll, PR D'Amico, AV Sartor, O TI Emerging role of adjuvant hormonal therapy - Discussion SO UROLOGY LA English DT Editorial Material C1 Univ Toronto, Toronto, ON, Canada. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Louisiana State Univ, New Orleans, LA USA. RP Klotz, L (reprint author), Univ Toronto, Toronto, ON, Canada. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 2002 VL 60 IS 3A SU S BP 21 EP 21 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100005 ER PT J AU Lee, WR Pollak, A Carroll, PR Klotz, L D'Amico, AV Kelly, WK Sartor, O Kantoff, PW AF Lee, WR Pollak, A Carroll, PR Klotz, L D'Amico, AV Kelly, WK Sartor, O Kantoff, PW TI Impact of androgen deprivation therapy on survival in men treated with radiation for prostate cancer - Discussion SO UROLOGY LA English DT Editorial Material ID RADIOTHERAPY C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Toronto, Toronto, ON, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Louisiana State Univ, New Orleans, LA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, WR (reprint author), Wake Forest Univ, Winston Salem, NC 27109 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 2002 VL 60 IS 3A SU S BP 30 EP 31 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100007 ER PT J AU D'Amico, AV AF D'Amico, AV TI Radiation and hormonal therapy for locally advanced and clinically localized prostate cancer SO UROLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on Newer Approaches to Androgen Deprivation Therapy in Prostate Cancer CY NOV 02-03, 2001 CL CAMBRIDGE, MASSACHUSETTS ID RADIOTHERAPY; CARCINOMA AB Patients with locally advanced prostate cancer (TNM clinical stage T3, T4) who were treated using external-beam radiotherapy (EBRT) and 3 years of androgen deprivation therapy (ADT) were compared with patients treated with EBRT alone and were shown to have a survival benefit. Studies that address the same question for patients with clinically localized disease (stage T1, T2) have been completed and are awaiting follow-up study. A rate of decrease in the serum hemoglobin level of greater than or equal to1 g/dL during the first month of neoadjuvant ADT predicted for a significantly worse disease-free survival outcome, as defined by the prostate-specific antigen, for patients with intermediate- and high-risk clinically localized disease who were undergoing EBRT and ADT. Validation of this predictive factor by others is needed. C1 Brigham & Womens Hosp, Dept Radiat Oncol, 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. NR 10 TC 18 Z9 19 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 SEP PY 2002 VL 60 IS 3A SU S BP 32 EP 37 AR PII S0090-4295(02)01566-2 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100008 PM 12231043 ER PT J AU Smith, MR D'Amico, AV Kelly, WK Pollack, A AF Smith, MR D'Amico, AV Kelly, WK Pollack, A TI Radiation and hormonal therapy for locally advanced and clinically localized prostate cancer - Discussion SO UROLOGY LA English DT Editorial Material ID RADIOTHERAPY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 2002 VL 60 IS 3A SU S BP 37 EP 38 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100009 ER PT J AU Kantoff, PW Klotz, L D'Amico, AV Smith, MR Carroll, PR AF Kantoff, PW Klotz, L D'Amico, AV Smith, MR Carroll, PR TI Preoperative neoadjuvant androgen withdrawal therapy in prostate cancer: The Canadian experience - Discussion SO UROLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Toronto, Toronto, ON, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 2002 VL 60 IS 3A SU S BP 51 EP 51 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100013 ER PT J AU Oh, WK Klotz, L Smith, MR Carroll, PR McLeod, DG Sartor, O AF Oh, WK Klotz, L Smith, MR Carroll, PR McLeod, DG Sartor, O TI Intermittent androgen suppression in prostate cancer: The Canadian experience - Discussion SO UROLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Toronto, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Louisiana State Univ, New Orleans, LA USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 2002 VL 60 IS 3A SU S BP 56 EP 56 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100015 ER PT J AU Sartor, O Grossfeld, GD Kantoff, PW Pollack, A Carroll, PR Lee, WR Klotz, L AF Sartor, O Grossfeld, GD Kantoff, PW Pollack, A Carroll, PR Lee, WR Klotz, L TI Patterns of failure after primary local therapy for prostate cancer and rationale for secondary therapy - Discussion SO UROLOGY LA English DT Editorial Material C1 Louisiana State Univ, New Orleans, LA 70112 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Toronto, Toronto, ON, Canada. RP Sartor, O (reprint author), Louisiana State Univ, New Orleans, LA 70112 USA. NR 0 TC 1 Z9 1 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 SEP PY 2002 VL 60 IS 3A SU S BP 62 EP 63 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100017 ER PT J AU Smith, MR AF Smith, MR TI Osteoporosis during androgen deprivation therapy for prostate cancer SO UROLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on Newer Approaches to Androgen Deprivation Therapy in Prostate Cancer CY NOV 02-03, 2001 CL CAMBRIDGE, MASSACHUSETTS ID BONE-MINERAL DENSITY; ESTROGEN-RECEPTOR GENE; X-RAY ABSORPTIOMETRY; OLDER MEN; HORMONE AGONISTS; LONGITUDINAL EVALUATION; AROMATASE DEFICIENCY; RANCHO BERNARDO; SEX STEROIDS; VITAMIN-D AB Osteoporosis is an important complication of androgen deprivation therapy (ADT). ADT by either orchiectomy or treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases fracture risk. Other factors, including diet and lifestyle, may contribute to bone loss in men with prostate cancer. Routine osteoporosis screening in men with prostate cancer is appropriate based on the high prevalence of osteoporosis. There is limited information about the best strategy to treat or prevent bone loss during ADT. Lifestyle modification, including smoking cessation, moderate alcohol consumption, and regular weight-bearing exercise should be encouraged. Supplemental calcium and vitamin D are also recommended. Additional treatment is warranted for men with osteoporosis, fractures, or high rates of bone loss during ADT. Pamidronate, an intravenous bisphosphonate, prevents bone loss during ADT. Other bisphosphonates are probably effective, although they have not been evaluated in this clinical setting. Alternative forms of hormonal therapy, including bicalutamide monotherapy, may cause less bone loss than ADT. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 61 TC 59 Z9 61 U1 1 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 SEP PY 2002 VL 60 IS 3A SU S BP 79 EP 85 AR PII S0090-4295(02)01579-0 DI 10.1016/S0090-4295(02)01579-0 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100021 PM 12231056 ER PT J AU Oh, WK AF Oh, WK TI Secondary hormonal therapies in the treatment of prostate cancer SO UROLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on Newer Approaches to Androgen Deprivation Therapy in Prostate Cancer CY NOV 02-03, 2001 CL CAMBRIDGE, MASSACHUSETTS ID ANTIANDROGEN WITHDRAWAL SYNDROME; PHASE-II TRIAL; PC-SPES; FLUTAMIDE WITHDRAWAL; MEGESTROL-ACETATE; ANTIGEN DECLINE; IN-VITRO; KETOCONAZOLE; BICALUTAMIDE; CARCINOMA AB Patients with androgen-independent prostate cancer demonstrate progression of disease, despite chemical or surgical castration, and have a poor prognosis. Cancer progression may be manifest as an asymptomatic increase in serum prostate-specific antigen (PSA) or may be accompanied by symptomatic and/or radiographic evidence of tumor growth. Observation remains a reasonable choice for asymptomatic patients. However, many patients remain anxious about withholding further treatment and, although studies have not demonstrated a survival benefit with second-line hormonal therapy, it may be appropriate to consider these therapies. In patients who have radiographic and/or symptomatic progression, the use of second-line hormonal therapy is more easily justified. Treatment options include: (1) secondary use of antiandrogens (eg, high-dose bicalutamide), (2) therapies targeted against adrenal steroid synthesis (eg, ketoconazole, aminoglutethimide, and corticosteroids), and (3) estrogenic therapies (eg, diethylstilbestrol). Symptomatic improvement and PSA-level decreases of greater than or equal to50% have been reported in approximately 20% to 80% of patients with androgen-independent prostate cancer who receive such second-line hormone therapies, with a typical response duration of 2 to 6 months. Toxicity is generally mild for these oral therapies, although serious side effects, including adrenal insufficiency, liver toxicity, and thrombosis, may occur. In conclusion, secondary hormonal therapies have a significant role in the treatment of patients with androgen-independent prostate cancer. Further research is needed to understand their optimal use. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Dept Adult Oncol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 36 TC 43 Z9 44 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 2002 VL 60 IS 3A SU S BP 87 EP 92 AR PII S0090-4295(02)01581-9 DI 10.1016/S0090-4295(02)01581-9 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100023 PM 12231058 ER PT J AU Gilligan, T Kantoff, PW AF Gilligan, T Kantoff, PW TI Chemotherapy for prostate cancer SO UROLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on Newer Approaches to Androgen Deprivation Therapy in Prostate Cancer CY NOV 02-03, 2001 CL CAMBRIDGE, MASSACHUSETTS ID PHASE-II TRIAL; ORAL ESTRAMUSTINE PHOSPHATE; RADICAL PROSTATECTOMY; DOCETAXEL TAXOTERE; ONCOLOGY-GROUP; CELL-LINES; ETOPOSIDE; ANTIGEN; MITOXANTRONE; THERAPY AB Androgen deprivation therapy remains the mainstay of therapy for patients with advanced prostate cancer and for selected patients with localized prostate cancer. Androgen deprivation therapy is the model of target-based therapies in this disease. Although it is clear that other target-based therapies need to be developed, cytotoxic chemotherapy is emerging as an effective form of treatment for men with prostate cancer. The early studies combining mitoxantrone plus a corticosteroid demonstrated that chemotherapy could be given to men with symptomatic hormone-refractory prostate cancer with minimal toxicity, and significant palliation could be provided. Since then, it has been recognized that estramustine, when combined with a variety of microtubular inhibitors, is very active in hormone-refractory prostate cancer. Doublets combining estramustine plus a taxane seem to be the most active. Although it appears that estramustine may add some activity to taxanes, the mechanism of its activity is uncertain, and its overall value is similarly questioned, particularly in light of its significant toxicity. Regimens that omit estramustine are being explored (ie, either taxane alone or taxane plus biologic agents). In addition, triplet therapy (combining estramustine plus a taxane plus a third drug, such as carboplatin or etoposide) is being explored. Finally, the utility of chemotherapy is beginning to be explored in the context of earlier disease in the neoadjuvant, adjuvant, or serologically relapsing group of patients. Data from these studies are just beginning to be gathered. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Kantoff, PW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. OI Gilligan, Timothy/0000-0003-2308-9303 NR 46 TC 76 Z9 77 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 SEP PY 2002 VL 60 IS 3A SU S BP 94 EP 100 AR PII S0090-4295(02)01583-2 DI 10.1016/S0090-4295(02)01583-2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100025 PM 12231060 ER PT J AU George, DJ AF George, DJ TI Receptor tyrosine kinases as rational targets for prostate cancer treatment: Platelet-derived growth factor receptor and imatinib mesylate SO UROLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on Newer Approaches to Androgen Deprivation Therapy in Prostate Cancer CY NOV 02-03, 2001 CL CAMBRIDGE, MASSACHUSETTS ID FACTOR-B CHAINS; BETA-RECEPTOR; FACTOR-A; IN-VIVO; HUMAN MENINGIOMAS; INHIBITOR STI571; MESSENGER-RNAS; ALPHA-RECEPTOR; PDGF RECEPTORS; EXPRESSION AB Over the past 15 years, numerous signal transduction pathways have been elucidated whose dysregulation may play an important role in the growth and survival of cancer cells. The success of imatinib mesylate (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ), a small molecule that inhibits the activation of the BCR-Abl oncogene in the treatment of chronic myelogenous leukemia, has demonstrated how effective targeted strategies can be when properly applied. With the hope of selectively targeting other critical components of cancer growth and survival while minimizing toxicity to the host, numerous strategies have been developed to inhibit receptor tyrosine kinases for various growth factors commonly expressed by cancer cells. Success of targeted inhibitors is inherently dependent on the proper selection of patients whose tumors are dependent on these growth factor pathways. Unfortunately, in prostate cancer, such selection has been a difficult-to-impossible task to date. Because of the vast number of mutational events, it is difficult to demonstrate that any particular growth factor signaling pathway is critical. In addition, because of the type (mostly bone only) and nature (usually small foci) of metastases, limited access to tumor tissue in the advanced cancer population has hampered attempts to characterize patients by their molecular features or phenotype. This article will focus on defining alternative criteria for a rational drug target and novel study designs for testing these agents in prostate cancer. In particular, the neoadjuvant setting represents a unique opportunity for new drug development in prostate cancer. An example of a neoadjuvant study testing, imatinib mesylate, is presented to display the advantages and limitations of this study design. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP George, DJ (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. NR 36 TC 36 Z9 37 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 SEP PY 2002 VL 60 IS 3A SU S BP 115 EP 121 AR PII S0090-4295(02)01589-3 DI 10.1016/S0090-4295(02)01589-3 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 597HX UT WOS:000178217100031 PM 12231066 ER PT J AU Yoon, JH Chen, MH Renshaw, AA Richie, JP D'Amico, AV AF Yoon, JH Chen, MH Renshaw, AA Richie, JP D'Amico, AV TI Predictive factor analysis as the basis for the clinical utility of percent positive prostate biopsies in patients with intermediate-risk prostate cancer SO UROLOGY LA English DT Article ID ANTIGEN DOUBLING TIMES; RADICAL PROSTATECTOMY; PATHOLOGICAL STAGE; GLEASON SCORE; DNA-PLOIDY; RECURRENCE; VOLUME; CARCINOMA; SPECIMENS; GRADE AB Objectives. To define the clinical reason for the further refinement of stratification of prostate-specific antigen (PSA) outcome using percent positive prostate biopsies in intermediate-risk patients. Methods. A chi-square metric was used to compare the distribution of pretreatment clinical and post-treatment pathologic factors for patients with intermediate-risk prostate cancer with 50% or less versus greater than 50% positive prostate biopsies. The PSA outcome stratified by the percent positive biopsies was calculated according to the Kaplan-Meier actuarial method. Comparisons of actuarial PSA failure-free survival were performed using the log-rank test. Results. The group with greater than 50% positive biopsies for prostate cancer had a significantly higher proportion of patients with pretreatment PSA values greater than 10 to 20 ng/mL(P = 0.01), biopsy Gleason score 4+3 (P = 0.05), and 1992 American Joint Committee on Cancer clinical category T2b (P = 0.01) than did the group with less than 50% positive biopsies. The group with greater than 50% positive biopsies also had a significantly higher proportion of patients with prostatectomy Gleason score 4+3 or higher (P = 0.001), pathologic Stage T3b (P < 0.0001), and rate of positive surgical margins (P = 0.002) than did the group of patients with less than 50% positive biopsies. Conclusions. The results of this study provide an explanation on the basis of the pretreatment and post-treatment predictive factors for the difference in PSA outcome for intermediate-risk patients when stratified by the percent positive biopsies. C1 Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Connecticut, Dept Biostat, Farmington, CT USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Yoon, JH (reprint author), Brigham & Womens Hosp, Dept Urol, 45 Francis St,ASB-II,3rd Floor, Boston, MA 02115 USA. NR 22 TC 13 Z9 13 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 SEP PY 2002 VL 60 IS 3 BP 454 EP 457 AR PII S0090-4295(02)01770-3 DI 10.1016/S0090-4295(02)01770-3 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 595LV UT WOS:000178111600022 PM 12350483 ER PT J AU Ung, JO Richie, JP Chen, MH Renshaw, AA D'Amico, AV AF Ung, JO Richie, JP Chen, MH Renshaw, AA D'Amico, AV TI Evolution of the presentation and pathologic and biochemical outcomes after radical prostatectomy for patients with clinically localized prostate cancer diagnosed during the PSA era SO UROLOGY LA English DT Article ID RETROPUBIC PROSTATECTOMY; STAGE T1C; ANTIGEN; RATES; MEN; PROGRESSION AB Objectives. To demonstrate the evolution of the clinical presentation and pathologic and biochemical outcomes for patients with clinically localized prostate cancer treated with radical prostatectomy during the prostate-specific antigen (PSA) era. Methods. One thousand fifty-nine consecutive men treated with radical prostatectomy from January 1989 to December 2000 comprised the study cohort. A chi-squared metric was used to compare the proportions of patients during three intervals (1989 to 1992, 1993 to 1996, and 1997 to 2000) by categories of PSA level, biopsy Gleason score, clinical T stage, percent positive biopsy cores, age, and risk group, as well as pathologic T stage, Gleason score, margin status, and lymph node status. Actual 2-year PSA recurrence-free survival rates are reported for patients with a minimal follow-up of 24 months, stratified by the interval and preoperative risk group. Results. There was a significant shift in the preoperative characteristics toward younger patients (P <0.0001) with nonpalpable disease (P <0.0001), lower PSA levels (P <0.0001), fewer percent positive biopsies (P <0.0001), and lower preoperative risk group classification (P <0.0001). Pathologically, a significant downward stage migration was found toward organ-confined disease (P <0.0001) and improvement in surgical margin status (P < 0.001). The actual 2-year PSA recurrence-free survival rates improved during the three intervals spanning the PSA era from 60% to 78% and 82% (P <0.0001). Conclusions. With the introduction of serum PSA as a screening tool, we have noted an evolution toward a lower pathologic stage, grade, and improved PSA outcome. These findings provide further support that serum PSA screening increases the proportion of patients potentially curable after radical prostatectomy. C1 Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ung, JO (reprint author), Brigham & Womens Hosp, Dept Urol, 45 Francis St,ASB-II,3rd Floor, Boston, MA 02115 USA. NR 29 TC 92 Z9 94 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 SEP PY 2002 VL 60 IS 3 BP 458 EP 463 AR PII S0090-4295(02)01814-9 DI 10.1016/S0090-4295(02)01814-9 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 595LV UT WOS:000178111600023 PM 12350484 ER PT J AU Yeung, A Deguang, H AF Yeung, A Deguang, H TI Somatoform disorders SO WESTERN JOURNAL OF MEDICINE LA English DT Article AB When Ms M experienced an attack of severe pain in the office of her primary care practitioner, her physician contacted a psychiatrist for an immediate consultation. The psychiatrist rendered the diagnosis of panic disorder and recommended a treatment regimen involving an antidepressant agent, a benzodiazepine, and biweekly supportive and cognitive therapy. After 3 months of therapy, Ms M no longer had symptoms. The dosage of the benzodiazepine was tapered and she continued to be well for another 6 months while taking the antidepressant alone. Believing that she was cured, Ms M then discontinued the use of the antidepressant against the advice of her psychiatrist. Two months later, her symptoms recurred and she resumed taking the antidepressant. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02113 USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St, Boston, MA 02113 USA. NR 6 TC 4 Z9 4 U1 0 U2 1 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD SEP PY 2002 VL 176 IS 4 BP 253 EP 256 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 618XH UT WOS:000179442500011 PM 12208832 ER PT J AU Zerbini, LF Libermann, TA Ventura, AM AF Zerbini, LF Libermann, TA Ventura, AM TI Insertion of an exogenous domain in the adenovirus type 2 fiber globular region SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE adenovirus; fiber protein; knob domain ID MEDIATED GENE-TRANSFER; COXSACKIE-B VIRUSES; SMOOTH-MUSCLE CELLS; RECOMBINANT ADENOVIRUS; SEROTYPE-2 FIBER; BINDING DOMAIN; HEAD DOMAIN; RECEPTOR; PROTEIN; VECTOR AB Adenoviruses have been used for gene therapy or immunization due to their ability to efficiently infect a broad range of cells and tissues. These applications as well as specificity could be improved further by redirecting binding of the virus to specific cell types. In this regard, modification of viral genes encoding coat proteins is an option to achieve improvement in retargeting. In this report, we describe a substitution in the adenovirus type 2 fiber globular region by the 44 amino acid C4 domain of human immunodeficiency virus type 1 gp120. In vitro translation analysis and immunoprecipitation assays show that the incorporation of the C4 domain into the fiber protein does not ablate its trimerization property and demonstrates the availability of the C4 epitope for interaction with monoclonal anti-C4 antibody. The recombinant adenovirus containing this modified fiber was also characterized by immunoprecipitation with the same antibody, showing the viability of such kind of modification. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo, Brazil. New England Baptist Bone & Joint Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02115 USA. RP Zerbini, LF (reprint author), Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo, Brazil. RI Libermann, Towia/F-9866-2010; Zerbini, Luiz /B-7720-2015 FU NIDDK NIH HHS [R24 DK 58739] NR 50 TC 1 Z9 1 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 AUG 30 PY 2002 VL 296 IS 4 BP 897 EP 903 AR PII S0006-291X(02)02005-3 DI 10.1016/S0006-291X(02)02005-3 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 643WY UT WOS:000180887000018 PM 12200132 ER PT J AU Zhang, KH Davids, E Tarazi, FI Baldessarini, RJ AF Zhang, KH Davids, E Tarazi, FI Baldessarini, RJ TI Serotonin transporter binding increases in caudate-putamen and nucleus accumbens after neonatal 6-hydroxydopamine lesions in rats: implications for motor hyperactivity SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE motor hyperactivity; 6-hydroxydopamine; 5-hydroxytryptamine (5-HT) transporter; caudate-putamen; nucleus accumbens; development ID DEPLETING BRAIN-LESIONS; ADULT-RAT; LOCOMOTOR-ACTIVITY; DOPAMINE NEURONS; NEOSTRIATUM; HYPERINNERVATION; INNERVATION; DENERVATION; AMPHETAMINE; AFFERENTS AB We examined serotonin (5-HT) transporters in rat forebrain using quantitative autoradiography at three distinct developmental stages after neonatal 6-hydroxydopamine lesions. The lesions substantially increased 5-HT transporter binding in both caudate-putamen and nucleus accumbens, but not cerebral cortex. The effects reached maximal levels as early as postnatal day (PD) 24, and were sustained until early adulthood. Behavioral analyses indicated that neonatal lesions resulted in motor hyperactivity on PD 24, but not on PD 36 or 59. These findings suggest that excess 5-HT transporters reflect serotonin hyperinnervation reported to occur in lesioned rats, and may modulate motor hyperactivity. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Zhang, KH (reprint author), Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, 115 Mill St, Belmont, MA 02478 USA. NR 33 TC 21 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD AUG 30 PY 2002 VL 137 IS 2 BP 135 EP 138 AR PII S0165-3806(02)00436-4 DI 10.1016/S0165-3806(02)00436-4 PG 4 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 599LX UT WOS:000178337000004 ER PT J AU Tseng, YH Ueki, K Kriauciunas, KM Kahn, CR AF Tseng, YH Ueki, K Kriauciunas, KM Kahn, CR TI Differential roles of insulin receptor substrates in the anti-apoptotic function of insulin-like growth factor-1 and insulin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; FORKHEAD TRANSCRIPTION FACTOR; ELEMENT-BINDING PROTEIN; FACTOR-I RECEPTOR; BROWN ADIPOCYTES; SIGNALING PATHWAY; CELL-SURVIVAL; FACTOR FKHR; PHOSPHATIDYLINOSITOL 3'-KINASE; GLUCOSE-HOMEOSTASIS AB Insulin-like growth factor-1 (IGF-1) and insulin are known to prevent apoptosis. The signaling network of IGF-l and insulin occurs via multiple pathways involving different insulin receptor substrates (IRSs). To define their roles in the anti-apoptotic function of IGF-1 and insulin, we established brown pre-adipocyte cell lines from wild-type and IRS knockout (KO) animals. In response to 16 h of serum deprivation, IRS-1-deficient cells showed a significant decrease in response to IGF-1 protection from apoptosis, whereas no changes were observed in the IRS-2, IRS-3, or IRS-4 KO cells. Five hours after serum withdrawal, cells already began to undergo apoptosis. At this early time point, IGF-l and insulin were able to protect both wild-type and IRS-1 KO cells from death by 85-90%. After a longer period of serum deprivation, the protective ability of insulin and IGF-1 was decreased, and this was especially reduced in the IRS-1 KO cells. Reconstitution of these cells with IRS-1, IRS-2, IRS-3, or IRS-1/IRS-2 chimeras restored the anti-apoptotic effects of IGF-1, whereas overexpression of IRS-4 had no effect at long time points and actually reduced the effect of IGF-1 at the short time point. The biochemical basis of the defect in anti-apoptosis was not dependent on phosphorylation of mitogen-activated protein kinase; whereas phosphoinositide 3-kinase activity was decreased by 30% in IRS-1 KO cells. Akt phosphorylation was slightly reduced in these cells. Phosphorylation of the transcription factors cAMP response element-binding protein and FKHR by IGF-1 and insulin was markedly reduced in IRS-1 KO cells. In addition, both IGF-1 and insulin prevented caspase-3 cleavage in the wild-type cells, and this effect was greatly reduced in the IRS-1-deficient cells. These findings suggest that the IRS proteins may play differential roles in the anti-apoptotic effects of IGF-1 and insulin in brown pre-adipocytes, with IRS-1 being predominant, possibly acting through caspase-3-, CREB-, and FKHR-dependent mechanisms. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res,Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res,Dept Med, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK101183, DK33201, DK55545] NR 57 TC 76 Z9 78 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 AUG 30 PY 2002 VL 277 IS 35 BP 31601 EP 31611 DI 10.1074/jbc.M202932200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 588UB UT WOS:000177718700040 PM 12082100 ER PT J AU Chao, W Shen, Y Li, L Rosenzweig, A AF Chao, W Shen, Y Li, L Rosenzweig, A TI Importance of FADD signaling in serum deprivation - and hypoxia-induced cardiomyocyte apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-DEATH; CARDIAC MYOCYTES; IN-VIVO; ACTIVATION; CASPASE-8; PATHWAY; GLUCOSE; SYSTEM; MITOCHONDRIA; INVOLVEMENT AB Although cardiomyocyte (CM) apoptosis has been well described in both in vitro and in vivo models of ischemic heart disease, the intracellular pathways leading to CM death have not been fully characterized. To define the role of death receptor signaling in CM apoptosis, we constructed recombinant adenoviral vectors carrying wild-type (wt) or dominant negative (dn) forms of the death receptor adaptor protein FADD (Fas-associated death domain protein) and used these vectors to transduce rat neonatal CMs in models of hypoxia- and serum deprivation (SD)-induced apoptosis. The combination of SD and hypoxia induced rapid activation of caspase-3 and -8 as well as DNA fragmentation, reaching a plateau within 4-8 h. Adenoviral expression of FADD-dn inhibited caspase-8 activation as well as hypoxia/SD-induced apoptosis at 24 h in an moi (multiplicity of infection)-dependent manner. In contrast, adenoviral expression of FADD-wt increased apoptosis and caspase-3 activity in CMs under both normoxic and hypoxic conditions. Surprisingly, FADD-dn, as well as the specific caspase-8 inhibitor benzyloxycarbonyl-IETD-fluoromethylketone also inhibited the activation of caspase-9 and -3 in CMs subjected to hypoxia/SD. These data suggest a primary role for FADD/caspase-8 signaling that is necessary and sufficient for apoptosis of CMs subjected to hypoxia/SD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy,Cardiovasc Res Ct, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp East, Program Cardiovasc Gene therapy, 114 16th St,Rm 2600, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-04336, HL-59521, HL-61557] NR 32 TC 48 Z9 50 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 AUG 30 PY 2002 VL 277 IS 35 BP 31639 EP 31645 DI 10.1074/jbc.M204104200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 588UB UT WOS:000177718700044 PM 12063258 ER PT J AU Shimada, M Chen, X Cvrk, T Hilfiker, H Parfenova, M Segre, GV AF Shimada, M Chen, X Cvrk, T Hilfiker, H Parfenova, M Segre, GV TI Purification and characterization of a receptor for human parathyroid hormone and parathyroid hormone-related peptide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; PHOTOAFFINITY CROSS-LINKING; FIRST EXTRACELLULAR LOOP; NMR SOLUTION STRUCTURE; PTH-RELATED PEPTIDE; (PTH)/PTH-RELATED PEPTIDE; BINDING DOMAIN; HUMORAL HYPERCALCEMIA; H-1-NMR SPECTROSCOPY; PTH/PTHRP RECEPTOR AB The human parathyroid hormone (PTH) receptor (hPTH1R), containing a 9-amino, acid sequence of rhodopsin at its C terminus, was transiently expressed in COS-7 cells and solubilized with 0.25% n-dodecyl maltoside. Approximately 18 mug of hPTH1R were purified to homogeneity per mg of crude membranes by single-step affinity chromatography using 1D4, a monoclonal antibody to a rhodopsin epitope. The N terminus of the hPTH1R is Tyr(23), consistent with removal of the 22-amino acid signal peptide. Comparisons of hPTH1R by quantitative immunoblotting and Scatchard analysis revealed that 75% of the receptors in membrane preparations were functional; there was little, if any, loss of functional receptors during purification. The binding affinity of the purified hPTH1R was slightly lower than membrane-embedded hPTH1R (K-d = 16.5 +/- 1.3 versus 11.9 +/- 1.9 nm), and the purified receptors bound rat [Nle(8,21),Tyr(34)]PTH-(1-34)-NH2 (PTH-(1-34)), and rat [Ile(5)Trp(23),Tyr(36)]PTHrP-(5-36)-NH2 with indistinguishable affinity. Maximal displacement of I-125-PTH-(1-34) binding by rat [alpha-aminoisobutyric acid (Aib)(1,3),Nle(8),Gln(10),Har(11),Ala(12),Trp(14),Arg(19),Tyr(21)]PTH-(1-21)-NH2 and rat Aib(1,3),Gln(10),Ha(11),Ala(12),Trp(14)]PTH-(1-14)-NH2 of 80 and 10%, respectively, indicates that both N-terminal and juxtamembrane ligand binding determinants are functional in the purified hPTH1R. Finally, PTH stimulated [S-35]GTPgammaS incorporation into Galpha(s) in a time- and dose-dependent manner, when recombinant hPTH1R, Galpha(s)-, and betagamma-subunits were reconstituted in phospholipid vesicles. The methods described will enable structural studies of the hPTH1R, and they provide an efficient and general technique to purify proteins, particularly those of the class 11 G protein-coupled receptor family. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Segre, GV (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 501, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-11794, DK-47034] NR 89 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 2002 VL 277 IS 35 BP 31774 EP 31780 DI 10.1074/bc.M204166200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 588UB UT WOS:000177718700059 PM 12080067 ER PT J AU Goncalves, J Silva, F Freitas-Vieira, A Santa-Marta, M Malho, R Yang, XY Gabuzda, D Barbas, C AF Goncalves, J Silva, F Freitas-Vieira, A Santa-Marta, M Malho, R Yang, XY Gabuzda, D Barbas, C TI Functional neutralization of HIV-1 Vif protein by intracellular immunization inhibits reverse transcription and viral replication SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL-DEPENDENT REQUIREMENT; VIVO GENE DELIVERY; TYPE-1 VIF; IN-VIVO; SOR GENE; LENTIVIRAL VECTOR; HUMAN-ANTIBODIES; DNA-SYNTHESIS; LIFE-CYCLE AB Human immunodeficiency virus type 1 (HIV-1)-encoded Vif protein is important for viral replication and infectivity. Vif is a cytoplasmic protein that acts during virus assembly by an unknown mechanism, enhancing viral infectivity. The action of Vif in producer cells is essential for the completion of proviral DNA synthesis following virus entry. Therefore, Vif is considered to be an important alternative therapeutic target for inhibition of viral infectivity at the level of viral assembly and reverse transcription. To gain insight into this process, we developed a Vif-specific single-chain antibody and expressed it intracellularly in the cytoplasm. This intrabody efficiently bound Vif protein and neutralized its infectivity-enhancing function. Intrabody-expressing cells were shown to be highly refractory to challenge with different strains of HIV-1 and HIV-1-infected cells. Inhibition of Vif by intrabody expression in the donor cell produced viral particles that do not complete reverse transcription in the recipient cell. The anti-Vif scFv was shown to be specific for Vif protein because its function was observed only in nonpermissive cells (H9, CEM, and U38). Moreover, transduction of peripheral blood mononuclear cells with an HIV-derived retroviral vector expressing Vif intrabody was shown to confer resistance to laboratory-adapted and primary HIV strains. This study provides biochemical evidence for the role of Vif in the HrV-1 lifecycle and validates Vif as a target for the control of HIV-1 infection. C1 Univ Lisbon, URIA Ctr Patogenese Mol, Fac Farm, P-1649019 Lisbon, Portugal. Univ Lisbon, Fac Ciencias Lisboa, Dept Plant Biol, P-1600 Lisbon, Portugal. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Goncalves, J (reprint author), Univ Lisbon, URIA Ctr Patogenese Mol, Fac Farm, Av Das Forcas Armadas, P-1649019 Lisbon, Portugal. RI Malho, Rui/I-4503-2012; Santa-Marta, Mariana/L-2407-2013; iMed.ULisboa, iMed.ULisboa/C-6292-2014; Goncalves, Joao/B-2013-2008; iMed.ULisboa, M2B /B-5277-2014 OI Malho, Rui/0000-0001-5287-869X; Santa-Marta, Mariana/0000-0002-0243-4158; Goncalves, Joao/0000-0002-1245-3715; FU NIAID NIH HHS [AI 36186, AI 37470] NR 54 TC 52 Z9 58 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 AUG 30 PY 2002 VL 277 IS 35 BP 32036 EP 32045 DI 10.1074/jbc.M201906200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 588UB UT WOS:000177718700092 PM 12039955 ER PT J AU Santiago, C Bjorling, E Stehle, T Casasnovas, JM AF Santiago, C Bjorling, E Stehle, T Casasnovas, JM TI Distinct kinetics for binding of the CD46 and SLAM receptors to overlapping sites in the measles virus hemagglutinin protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELLULAR RECEPTOR; CRYSTAL-STRUCTURE; AFFINITY; SURFACE; RECOGNITION; RHINOVIRUS; SUFFICIENT; FRAGMENTS; EPITOPES; DOMAINS AB Measles virus (MV) is a human pathogen using two distinct cell surface receptors for entry into host cells. We present here a comparative analysis for binding of the MV receptors CD46 and SLAM to the measles virus hemagglutinin protein (MVH, Edmonston strain). Soluble monomeric and dimeric MM variants were prepared in mammalian cells and their conformation assessed using a panel of monoclonal antibodies. The two receptor molecules specifically bound to the MVH protein with distinct binding modes. The association rate (k(a)) for SLAM binding to MVH was very low (similar to3000 M-1 s(-1)), about 20 times lower that the k(a) determined for CD46 binding. However, SLAM bound tighter to the virus protein than CD46, as revealed by a 5-fold lower dissociation rate (k(d), similar to1.5 x 10(-3) s(-1)). These data suggest that the SLAM receptor binds to a less accessible and more hydrophobic surface on MVH than the CD46 receptor, as illustrated in a binding model. Despite the differences in kinetics, receptor competition binding experiments revealed that they recognize overlapping sites in MVH. Indeed, a panel of anti-MVH monoclonal antibodies equally inhibited binding of both receptor molecules. The similar immune reactivity of the two receptor binding sites suggests that the shift in receptor usage by MV may not be driven by immune responses. C1 Karolinska Inst, Novum, Dept Biosci, Ctr Biotechnol, S-14157 Huddinge, Sweden. Karolinska Inst, Microbiol & Tumor Biol Ctr, S-17177 Stockholm, Sweden. Karolinska Inst, South Hosp, Res Ctr, S-11883 Stockholm, Sweden. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Casasnovas, JM (reprint author), Karolinska Inst, Novum, Dept Biosci, Ctr Biotechnol, S-14157 Huddinge, Sweden. RI Casasnovas, Jose/L-6299-2014; Santiago, Cesar/K-4240-2014 OI Casasnovas, Jose/0000-0002-2873-6410; Santiago, Cesar/0000-0002-5149-1722 FU NIAID NIH HHS [AI45716] NR 36 TC 51 Z9 53 U1 0 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 AUG 30 PY 2002 VL 277 IS 35 BP 32294 EP 32301 DI 10.1074/jbo.M202973200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 588UB UT WOS:000177718700124 PM 12065582 ER PT J AU Clark, RA Li, SL Pearson, DW Leidal, KG Clark, JR Denning, GM Reddick, R Krause, KH Valente, AJ AF Clark, RA Li, SL Pearson, DW Leidal, KG Clark, JR Denning, GM Reddick, R Krause, KH Valente, AJ TI Regulation of calreticulin expression during induction of differentiation in human myeloid cells - Evidence for remodeling of the endoplasmic reticulum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN DISULFIDE-ISOMERASE; RESPIRATORY BURST OXIDASE; CALCIUM-PUMP ISOFORMS; HEAT-SHOCK; CA2+ STORE; INTRACELLULAR-DISTRIBUTION; TRANSCRIPTIONAL REGULATION; FUNCTIONAL EXPRESSION; MOLECULAR CHAPERONE; CARDIAC DEVELOPMENT AB Induction of differentiation of HL-60 human myeloid cells profoundly affected expression of calreticulin, a Ca2+-binding endoplasmic reticulum chaperone. Induction with Me2SO or retinoic acid reduced levels of calreticulin protein by similar to60% within 4 days. Pulse-chase studies indicated that labeled calreticulin decayed at similar rates in differentiated and undifferentiated cells (t(1/2) similar to4.6 days), but the biosynthetic rate was <10% of control after 4 days. Differentiation also induced a rapid decline in calreticulin mRNA levels (90% reduction after 1 day) without a decrease in transcript stability (t(1/2) similar to5 h). Nuclear run-on analysis demonstrated rapid down-regulation of gene transcription (21% of control at 2 h). Differentiation also greatly reduced the Ca2+ content of the cells (25% of control), although residual Ca2+ pools remained sensitive to thapsigargin, ionomycin, and inositol trisphosphate. Progressive decreases were also observed in levels of calnexin and ERp57, whereas BiP/GRP78 and protein disulfide isomerase were only modestly affected. Ultrastructural studies showed a substantial reduction in endoplasmic reticulum content of the cells. Thus, terminal differentiation of myeloid cells was associated with decreased endoplasmic reticulum content, selective reductions in molecular chaperones, and diminished intracellular Ca2+ stores, perhaps reflecting an endoplasmic reticulum remodeling program as a prominent feature of granulocytic differentiation. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Dept Pathol, San Antonio, TX 78229 USA. Iowa City Vet Affairs Med Ctr, Dept Med, Iowa City, IA 52242 USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Geneva, Dept Med, CH-1225 Geneva, Switzerland. RP Clark, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Krause, Karl-Heinz/E-8030-2011 NR 65 TC 16 Z9 16 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 AUG 30 PY 2002 VL 277 IS 35 BP 32369 EP 32378 DI 10.1074/jbc.M205269200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 588UB UT WOS:000177718700133 PM 12065601 ER PT J AU Bang, PI Yelick, PC Malicki, JJ Sewell, WF AF Bang, PI Yelick, PC Malicki, JJ Sewell, WF TI High-throughput behavioral screening method for detecting auditory response defects in zebrafish SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE hearing; auditory system; startle response; hair cell; macula ID GOLDFISH CARASSIUS-AURATUS; MUTATIONS AFFECTING DEVELOPMENT; LATERAL LINE NERVES; MAUTHNER CELL; INNER-EAR; RETICULOSPINAL NEURONS; GENETIC-ANALYSIS; MOTTLED SCULPIN; ADULT ZEBRAFISH; COTTUS-BAIRDI AB We have developed an automated, high-throughput behavioral screening method for detecting hearing defects in zebrafish. Our assay monitors a rapid escape reflex in response to a loud sound. With this approach, 36 adult zebrafish, restrained in visually isolated compartments, can be simultaneously assessed for responsiveness to near-field 400 Hz sinusoidal tone bursts. Automated, objective determinations of responses are achieved with a computer program that obtains images at precise times relative to the acoustic stimulus. Images taken with a CCD video camera before and after stimulus presentation are subtracted to reveal a response to the sound. Up to 108 fish can be screened per hour. Over 6500 fish were tested to validate the reliability of the assay. We found that 1% of these animals displayed hearing deficits. The phenotypes of non-responders were further assessed with radiological analysis for defects in the gross morphology of the auditory system. Nearly all of those showed abnormalities in conductive elements of the auditory system: the swim bladder or Weberian ossicles. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Univ Hosp Geneva, Dept Otolaryngol, CH-1211 Geneva, Switzerland. RP Sewell, WF (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [HD-40190]; NIDCD NIH HHS [DC-00767] NR 45 TC 59 Z9 63 U1 0 U2 14 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 AUG 30 PY 2002 VL 118 IS 2 BP 177 EP 187 AR PII S0165-0270(02)00118-8 DI 10.1016/S0165-0270(02)00118-8 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 592ZQ UT WOS:000177967100008 PM 12204308 ER PT J AU Parzen, M Lipsitz, SR Ibrahim, JG Lipshultz, S AF Parzen, M Lipsitz, SR Ibrahim, JG Lipshultz, S TI A weighted estimating equation for linear regression with missing covariate data SO STATISTICS IN MEDICINE LA English DT Article DE missing at random; missing completely at random; missing data mechanism ID MAXIMUM-LIKELIHOOD; INCOMPLETE DATA; MODELS; EM AB Linear regression is one of the most popular statistical techniques. In linear regression analysis, missing covariate data occur often. A recent approach to analyse such data is a weighted estimating equation. With weighted estimating equations, the contribution to the estimating equation from a complete observation is weighted by the inverse 'probability of being observed'. In this paper, we propose a weighted estimating equation in which we wrongly assume that the missing covariates are multivariate normal, but still produces consistent estimates as long as the probability of being observed is correctly modelled. In simulations, these weighted estimating equations appear to be highly efficient when compared to the most efficient weighted estimating equation as proposed by Robins et al. and Lipsitz et al. However, these weighted estimating equations, in which we wrongly assume that the missing covariates are multivariate normal, are much less computationally intensive than the weighted estimating equations given by Lipsitz et al. We compare the weighted estimating equations proposed in this paper to the efficient weighted estimating equations via an example and a simulation study. We only consider missing data which are missing at random; non-ignorably missing data are not addressed in this paper. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Rochester, Ctr Med, Rochester, NY 14627 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. FU BHP HRSA HHS [AHRQ 10871]; NCI NIH HHS [CA 74015, CA 70101]; NHLBI NIH HHS [HL 69800, HL52329] NR 11 TC 9 Z9 9 U1 0 U2 2 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 AUG 30 PY 2002 VL 21 IS 16 BP 2421 EP 2436 DI 10.1002/sim.1195 PG 16 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 584GJ UT WOS:000177458600012 PM 12210626 ER PT J AU Young, JM Bennett, C Gilhooly, P Wessells, H Ramos, DE AF Young, JM Bennett, C Gilhooly, P Wessells, H Ramos, DE TI Efficacy and safety of sildenafil citrate (Viagra((R))) in black and Hispanic American men SO UROLOGY LA English DT Article ID ERECTILE DYSFUNCTION; ORAL SILDENAFIL; INTERNATIONAL INDEX; DOUBLE-BLIND; RISK-FACTORS; PREVALENCE AB The objective of this study was to assess the efficacy and safety of sildenafil citrate (Viagra) in black American and Hispanic American men with erectile dysfunction (ED) of broad-spectrum etiology. A total of 246 black American and 197 Hispanic American men were randomized to sildenafil (50 mg, adjustable to 25 mg or 100 mg, depending on efficacy and tolerability; n = 124 and n = 99, respectively) or matching placebo (n = 122 and n = 98, respectively). After 6 weeks, patients were given the option of switching to the other blinded treatment for the following 6 weeks. The 12 weeks of double-blind treatment were followed by 12 weeks of open-label extension. Despite differences in prevalence of hypertension, diabetes mellitus, hyperlipidemia, and use of concomitant anti hypertensive agents between the 2 study groups, sildenafil was efficacious and well tolerated. After 6 weeks, scores for questions 3 and 4 from the International Index of Erectile Function (IIEF) were significantly higher among sildenafil-treated black and Hispanic patients than in placebo-treated patients. In addition, compared with placebo, a significantly larger proportion of sildenafil patients reported improved erections and improved ability to have sexual intercourse. When efficacy results were stratified by ED severity or number of risk factors, scores for IIEF questions 3 and 4 were lower in men with severe ED versus mild-to-moderate ED. Similarly, the percentage of patients reporting improved erections decreased with ED severity and number of risk factors. The proportion of patients switching to the other treatment after 6 weeks was significantly higher in the placebo group (71% to 85%) than in the sildenafil group (27% to 28%). The most common adverse events included headache and vasodilation, which were mild to moderate in nature and were comparable between groups. These data demonstrate that despite differences in prevalence rates of comorbidities, efficacy and safety of sildenafil is maintained across different ethnic groups. C1 S Orange Cty Urol Med Associates, Laguna Woods, CA 92653 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Dept Vet Affairs, New Jersey Healthcare Syst, E Orange, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Washington, Seattle, WA 98195 USA. Pfizer Inc, New York, NY USA. RP Young, JM (reprint author), S Orange Cty Urol Med Associates, 24301 Paseo Valencia, Laguna Woods, CA 92653 USA. NR 25 TC 27 Z9 27 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 AUG 30 PY 2002 VL 60 IS 2B SU S BP 39 EP 48 AR PII S0090-4295(02)01689-8 DI 10.1016/S0090-4295(02)01689-8 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 597HW UT WOS:000178217000005 PM 12414332 ER PT J AU Nurnberg, HG Seidman, SN Gelenberg, AJ Fava, M Rosen, R Shabsigh, R AF Nurnberg, HG Seidman, SN Gelenberg, AJ Fava, M Rosen, R Shabsigh, R TI Depression, antidepressant therapies, and erectile dysfunction: Clinical trials of sildenafil citrate (Viagra((R))) in treated and untreated patients with depression SO UROLOGY LA English DT Article ID INDUCED SEXUAL DYSFUNCTION; NOCTURNAL PENILE TUMESCENCE; SPINAL-CORD INJURY; SEROTONIN REUPTAKE INHIBITORS; CORONARY-ARTERY DISEASE; RADICAL PROSTATECTOMY; MAJOR DEPRESSION; ORAL SILDENAFIL; PRIMARY-CARE; MEN AB Erectile dysfunction (ED) and depression are highly prevalent conditions and frequently occur concomitantly in predisposed individuals. Men with ED and depression are also likely to have other comorbid conditions, including diabetes, hypertension, and heart disease. Because ED is also a common adverse effect of some medications for these conditions, patients are frequently noncompliant with treatment. Sildenafil citrate (Viagra) is effective in treating ED of a broad range of etiologies, suggesting that it may be equally beneficial in patients with ED that is associated with depressive symptoms and in those with ED resulting from serotonergic reuptake inhibitor (SRI) antidepressant treatment. We review the results of 3 randomized, placebo-controlled trials and a retrospective analysis of data pooled from 10 clinical trials that examine the efficacy of sildenafil in treating ED associated with depression and as an adverse effect of SRI treatment. The results suggest that sildenafil is efficacious as a first-line treatment for ED in men with untreated minor depression, in men with ED that is refractory to successful SRI treatment of depression, and in those whose depression was successfully treated but who developed ED as a consequence of SRI treatment. Given the complex interrelations among ED, depression, and other comorbid conditions, the key to proper management is a comprehensive evaluation, including sexual function, and an accurate differential diagnosis. C1 Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA. Columbia Presbyterian Med Ctr, Dept Psychiat, New York, NY 10032 USA. Arizona Hlth Sci Ctr, Dept Psychiat, Tucson, AZ 85724 USA. Massachusetts Gen Hosp, Depress Clin & Res Ctr, Boston, MA 02114 USA. Robert Wood Johnson Med Sch, Dept Psychiat, Piscataway, NJ USA. Presbyterian Hosp, Dept Urol, New York, NY USA. RP Nurnberg, HG (reprint author), Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Psychiat, 2400 Tucker NE, Albuquerque, NM 87131 USA. NR 56 TC 35 Z9 38 U1 0 U2 5 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 AUG 30 PY 2002 VL 60 IS 2B SU S BP 58 EP 66 AR PII S0090-4295(02)01691-6 DI 10.1016/S0090-4295(02)01691-6 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 597HW UT WOS:000178217000007 PM 12414334 ER PT J AU Boes, M Cerny, J Massol, R Op den Brouw, M Kirchhausen, T Chen, JZ Ploegh, HL AF Boes, M Cerny, J Massol, R Op den Brouw, M Kirchhausen, T Chen, JZ Ploegh, HL TI T-cell engagement of dendritic cells rapidly rearranges MHC class II transport SO NATURE LA English DT Article ID ANTIGEN PRESENTATION; INVARIANT CHAIN; EXPRESSION; MICE; ACTIVATION; DEGRADATION; MOLECULES; COMPLEXES; GENES AB Assembly of major histocompatibility complex (MHC) molecules, which present antigen in the form of short peptides to T lymphocytes, occurs in the endoplasmic reticulum; once assembled, these molecules travel from the endoplasmic reticulum to their final destination. MHC class II molecules follow a route that takes them by means of the endocytic pathway, where they acquire peptide, to the cell surface(1). The transport of MHC class II molecules in 'professional' antigen-presenting cells (APCs) is subject to tight control and responds to inflammatory stimuli such as lipopolysaccharide. To study class II transport in live APCs, we replaced the mouse MHC class II gene with a version that codes for a class II molecule tagged with enhanced green fluorescent protein (EGFP). The resulting mice are immunologically indistinguishable from wild type. In bone-marrow-derived dendritic cells, we observed class II molecules in late endocytic structures with transport patterns similar to those in Langerhans cells observed in situ. We show that tubular endosomes extend intracellularly and polarize towards the interacting T cell, but only when antigen-laden dendritic cells encounter T cells of the appropriate specificity. We propose that such tubulation serves to facilitate the ensuing T-cell response. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Charles Univ, Fac Sci, Prague, Van Cerny, Czech Republic. RP Ploegh, HL (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Cerny, Jan/C-1887-2012 NR 22 TC 277 Z9 285 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 29 PY 2002 VL 418 IS 6901 BP 983 EP 988 DI 10.1038/nature01004 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 588AP UT WOS:000177677500046 PM 12198548 ER PT J AU Zhang, ZQ Wang, Y Herzog, CR Liu, GJ Lee, HW DePinho, RA You, M AF Zhang, ZQ Wang, Y Herzog, CR Liu, GJ Lee, HW DePinho, RA You, M TI A strong candidate gene for the Papg1 locus on mouse chromosome 4 affecting lung tumor progression SO ONCOGENE LA English DT Article DE Cdkn2a; p16(INK4a); ARF; genetic variants; mouse lung tumors; pulmonary adenoma progression 1; quantitative trait locus ID CELL-CYCLE CONTROL; SUPPRESSOR GENE; PLASMACYTOMA SUSCEPTIBILITY; STABILIZES P53; MDM2; P19(ARF); CANCER; P16(INK4A); CDKN2A; MICE AB Lung cancer is the leading cause of cancer death among both men and women, accounting for more than 28% of all cancer deaths. In fact, more people die of lung cancer than of colon, breast, and prostate cancers combined. Although lung cancer is largely induced by smoking, there is strong evidence for genetic susceptibility and gene-environment interactions in the development of lung cancer. Inbred mouse models offer an effective means of identifying candidate lung cancer susceptibility loci since genetic heterogeneity and enormous variation in exposure levels to environmental agents make it difficult to identify lung cancer susceptibility loci in humans. Papg-1 (pulmonary adenoma progression 1) was previously mapped to a region on mouse chromosome 4. This locus contains a candidate gene, Cdkn2a also referred to as Ink4a/Arf, which dually encodes two established tumor suppressors p16(INK4a) and ARE Cdkn2a became a primary candidate for Papg-1 for two reasons: (1) two haplotypes of mouse Cdkn2a were found to segregate with differential genetic susceptibility to lung tumor progression in mice; and (2) in vitro studies showed that the p16(INK4a) allele from the BALB/cJ mouse had a significantly decreased ability to bind and inhibit CDK6 and to suppress cell growth when compared with the p16(INK4a) allele from the A/J mouse. Here, we report that mice with a heterozygous deficiency for the A/J Cdkn2a allele were significantly more susceptible to lung tumor progression than mice with a heterozygous deficiency for a BALB/cJ Cdkn2a allele, when compared to their respective wild type mice. These results offer strong evidence that naturally occurring variation of p16(INK4a) influences susceptibility to enhance lung tumor progression making it a strong candidate for the lung tumor progression locus, Papg-1. C1 Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. Ohio State Univ, Sch Publ Hlth, Ctr Comprehens Canc, Columbus, OH 43210 USA. Amer Hlth Fdn, Valhalla, NY 10595 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP You, M (reprint author), Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, 420 W 12th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [R01CA78797, P30CA16058, R01CA58554] NR 32 TC 16 Z9 17 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 29 PY 2002 VL 21 IS 38 BP 5960 EP 5966 DI 10.1038/sj.onc.1205725 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 585JD UT WOS:000177520900019 PM 12185599 ER PT J AU Steere, AC Burns, RB AF Steere, AC Burns, RB TI A 58-year-old man with a diagnosis of chronic Lyme disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; RANDOMIZED CONTROLLED TRIAL; COGNITIVE-BEHAVIOR THERAPY; POLYMERASE CHAIN-REACTION; BORRELIA-BURGDORFERI DNA; DOUBLE-BLIND; ERYTHEMA MIGRANS; NEUROLOGIC MANIFESTATIONS; FIBROMYALGIA SYNDROME; ANTIBIOTIC-TREATMENT C1 Massachusetts Gen Hosp, Comprehens Arthrit Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Steere, AC (reprint author), Massachusetts Gen Hosp, Comprehens Arthrit Ctr, 149 13th St,Room 8301, Charlestown, MA 02129 USA. NR 79 TC 9 Z9 9 U1 1 U2 2 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 AUG 28 PY 2002 VL 288 IS 8 BP 1002 EP 1010 DI 10.1001/jama.288.8.1002 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 587RM UT WOS:000177656400026 PM 12190371 ER PT J AU Mehta, RH Manfredini, R Hassan, F Sechtem, U Bossone, E Oh, JK Cooper, JV Smith, DE Portaluppi, F Penn, M Hutchison, SD Nienaber, CA Isselbacher, EM Eagle, KA AF Mehta, RH Manfredini, R Hassan, F Sechtem, U Bossone, E Oh, JK Cooper, JV Smith, DE Portaluppi, F Penn, M Hutchison, SD Nienaber, CA Isselbacher, EM Eagle, KA CA Int Registry Acute Aortic Dissection TI Chronobiological patterns of acute aortic dissection SO CIRCULATION LA English DT Article DE aorta; circadian rhythm; seasons ID ACUTE MYOCARDIAL-INFARCTION; SUDDEN CARDIAC DEATH; CIRCADIAN VARIATION; SEASONAL-VARIATION; THORACIC AORTA; RUPTURE; ONSET; RISK; RHYTHMICITY; POPULATION AB Background-Chronobiological rhythms have been shown to influence the occurrence of a variety of cardiovascular disorders. However, the effects of the time of the day, the day of the week, or monthly/seasonal changes on acute aortic dissection (AAD) have not been well studied. Methods and Results-Accordingly, we evaluated 957 patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2000 (mean age 62 14 years, type A 61%). A chi(2) test for goodness of fit and partial Fourier analysis were used to evaluate nonuniformity and rhythmicity of AAD during circadian, weekly, and monthly periods. A significantly higher frequency of AAD occurred from 6:00 AM to 12:00 noon compared with other time periods (12:00 noon to 6:00 Pm, 6:00 Pm to 12:00 midnight, and 12:00 midnight to 6:00 AM; P<0.001 by X, test). Fourier analysis showed a highly significant circadian variation (P<0.001) with a peak between 8:00 Am and 9:00 AM. Although no significant variation was found for the day of the week, the frequency of AAD was significantly higher during winter (P=0.008 versus other seasons by chi(2) test). Fourier analysis confirmed this monthly variation with a peak in January (P<0.001). Subgroup analysis identified a significant association for all subgroups with circadian rhythmicity. However, seasonal/monthly variations were observed only among patients aged <70 years, those with type B AAD, and those without hypertension or diabetes. Conclusions-Similar to other cardiovascular conditions, AAD exhibits significant circadian and seasonal/monthly variations. Our findings may have important implications for the prevention of AAD by tailoring treatment strategies to ensure maximal benefits during the vulnerable periods. C1 Univ Michigan, Div Cardiol, Ann Arbor, MI 48109 USA. Univ Ferrara, Internal Med & Hypertens Ctr 1, I-44100 Ferrara, Italy. Robert Bosch Krankenhaus, Div Cardiol, Stuttgart, Germany. Mayo Clin, Div Cardiol, Rochester, MN USA. Cleveland Clin Fdn, Div Cardiol, Cleveland, OH 44195 USA. St Michaels Hosp, Div Cardiol, Toronto, ON M5B 1W8, Canada. Univ Rostock, Div Cardiol, Rostock, Germany. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mehta, RH (reprint author), 2215 Fuller Rd,7E 111A, Ann Arbor, MI 48105 USA. RI Portaluppi, Francesco/H-2206-2012 OI Portaluppi, Francesco/0000-0002-2948-1579 NR 26 TC 121 Z9 128 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 27 PY 2002 VL 106 IS 9 BP 1110 EP 1115 DI 10.1161/01.CIR.0000027568.39540.4B PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 590AK UT WOS:000177794800024 PM 12196337 ER PT J AU Martin, F Sanchez, PL Doherty, E Colon-Hernandez, PJ Delgado, G Inglessis, I Scott, N Hung, J King, MEE Buonanno, F Demirjian, Z de Moor, M Palacios, IF AF Martin, F Sanchez, PL Doherty, E Colon-Hernandez, PJ Delgado, G Inglessis, I Scott, N Hung, J King, MEE Buonanno, F Demirjian, Z de Moor, M Palacios, IF TI Percutaneous transcatheter closure of patent foramen ovale in patients with paradoxical embolism SO CIRCULATION LA English DT Article DE heart septal defects; embolism; catheterization; stroke ID ATRIAL SEPTAL ANEURYSM; RECURRENT CEREBROVASCULAR EVENTS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CRYPTOGENIC STROKE; SURGICAL CLOSURE; DECOMPRESSION-SICKNESS; ISCHEMIC EVENTS; TERM RISK; PREVENTION; DEFECT AB Background-Percutaneous transcatheter closure of patent foramen ovale (PFO) is used as an alternative to surgery or long-term anticoagulation for the treatment of patients with paradoxical embolism and PFO. Methods and Results-We report the immediate and long-term clinical and echocardiographic outcome of 110 consecutive patients (58 males, mean age 47 +/- 14 years) who underwent transcatheter closure of PFO because of paradoxical embolism between 1995 and 2001. Procedural success, defined as successful deployment of the device and effective occlusion (no, or trivial, shunt after device placement), was achieved in all (100%) patients. There was no in-hospital mortality, 1 device migration requiring surgical intervention (0.9%), and 1 episode of cardiac tamponade (0.9%) requiring pericardiocentesis. A progressive increment in full occlusion was observed (44%, 51%, 66%, and 71% at 1 day, 6 months, and 1 and 2 years, respectively, after device placement). At a mean follow-up of 2.3 years, 2 patients experienced recurrent neurological events (1 fatal stroke and 1 transient ischemic attack), representing an annual risk of recurrence of 0.9%. In addition, 4 (3.6%) of the patients required reintervention for device malalignment or significant shunt. Kaplan-Meier analysis showed a freedom from recurrent embolic events and reintervention of 96% and 90% at 1 and 5 years, respectively. Conclusions-Transcatheter closure of PFO is a safe and effective therapy for patients with paradoxical embolism and PFO. It is associated with a high success rate, low incidence of hospital complications, and low frequency of recurrent systemic embolic events. C1 Harvard Univ, Massachusetts Gen Hosp,Sch Med, Cardiac Catheterizat Lab & Intervent Cardiol, Cardiac Unit,Dept Med, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp,Sch Med, Cardiac Catheterizat Lab & Intervent Cardiol, Cardiac Unit,Dept Med, Bulfinch 105,Fruit St, Boston, MA 02114 USA. OI Sanchez, Pedro L/0000-0002-4288-345X NR 31 TC 215 Z9 223 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 27 PY 2002 VL 106 IS 9 BP 1121 EP 1126 DI 10.1161/01.CIR.0000027819.19722.EE PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 590AK UT WOS:000177794800026 PM 12196339 ER PT J AU Kelly, PJ Rosand, J Kistler, JP Shih, VE Silveira, S Plomaritoglou, A Furie, KL AF Kelly, PJ Rosand, J Kistler, JP Shih, VE Silveira, S Plomaritoglou, A Furie, KL TI Homocysteine, MTHFR 677C -> T polymorphism, and risk of ischemic stroke - Results of a meta-analysis SO NEUROLOGY LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; CAROTID-ARTERY STENOSIS; FACTOR-V-LEIDEN; PLASMA HOMOCYSTEINE; CEREBROVASCULAR-DISEASE; CEREBRAL INFARCTION; VASCULAR-DISEASE; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; HOMOCYST(E)INE CONCENTRATION; SERUM HOMOCYSTEINE AB Background: Data are conflicting concerning risk for ischemic stroke associated with hyperhomocyst(e)inemia (hyper-Hcy) and a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which predisposes to hyper-Hcy in vivo. Methods: Search of MEDLINE, Science Citation Index, and abstracts of conference proceedings revealed relevant articles. Exposure was defined as follows: 1) prevalence of hyper-Hey; 2) absolute difference in the mean Hey concentration between subjects with and without ischemic stroke; and 3) the MTHFR TT genotype frequency. Outcome was defined as ischemic stroke with or without neuroimaging. Inclusion criteria were retrospective and prospective studies with reported odds ratios (OR) or hazard ratios (HR) or arithmetic mean Hey levels. Exclusion criteria were absence of OR or HR, outcome defined as carotid atherosclerosis or intima-media thickening, stroke in patients younger than 18 years old, and studies in languages other than English. Statistical analyses for between-study heterogeneity and pooled risk estimates were performed using Stata software (Stata Corporation, College Station, TX). Results: Among 16 studies (1,487 stroke and 2,554 nonstroke cases), the pooled mean Hey level in patients with ischemic stoke was 2.32 mumol/L (95% CI, 1.6 to 3.04; p < 0.001) greater than that in those without ischemic stroke.. Among 14 included studies (1,769 stroke and 7,400 nonstroke cases), the pooled OR estimate of ischemic stroke associated with hyper-Hcy was 1.79 (95% CI, 1.61 to 2.0; p < 0.001). Among 19 included studies (2,788 stroke and 3,962 nonstroke cases), the OR associated with the TT genotype was 1.23 (95% CI, 0.96 to 1.58; p = 0.1). Conclusion: These data support an association between mild-to-moderate hyper-Hcy and ischemic stoke. The MTHFR TT genotype may have a small influence in determining susceptibility to ischemic stoke. C1 Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Amino Acid Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. RP Kelly, PJ (reprint author), Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, VBK 802,Fruit St, Boston, MA 02114 USA. NR 67 TC 153 Z9 173 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 27 PY 2002 VL 59 IS 4 BP 529 EP 536 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 586YJ UT WOS:000177613500011 PM 12196644 ER PT J AU Breedveld, GJ Percy, AK MacDonald, ME De Vries, BBA Yapijakis, C Dure, LS Ippel, EF Sandkuijl, LA Heutink, P Arts, WFM AF Breedveld, GJ Percy, AK MacDonald, ME De Vries, BBA Yapijakis, C Dure, LS Ippel, EF Sandkuijl, LA Heutink, P Arts, WFM TI Clinical and genetic heterogeneity in benign hereditary chorea SO NEUROLOGY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; HUNTINGTONS-DISEASE; PROTEIN SIP1; EARLY-ONSET; FAMILY; IDENTIFICATION; SMN AB Background: Benign hereditary chorea (BHC) is an autosomal dominant disorder that can be distinguished from Huntington disease by its early onset, stable or only slightly progressive course, and absence of mental deterioration. The variation in clinical features is such that its very existence has been doubted. The authors recently described the localization of a gene responsible for BHC on chromosome 14q in a large Dutch family. Objective: To report results of extensive clinical and linkage analyses for this Dutch family and six other families with BHC. Results: Three of the seven families had linkage to a region on chromosome 14q13.1-q21.1. HOMOG analysis showed odds of 10 x 10(11) in favor of locus heterogeneity. Haplotype analyses for the linked families resulted in a reduction of the critical interval for the BHC gene to 8.4 cM between marker D14S49 and marker D14S278. Clinically, these three families had a homogeneous picture with early-onset chorea, sometimes accompanied by slight ataxia in walking, but without dystonia, myoclonic jerks, or dysarthria. The severity of the choreatic movements tended to abate in adolescence or early adulthood. In the unlinked families, symptoms and signs were more heterogeneous as to age at onset and the occurrence of myoclonic jerks or dystonia. Conclusions: BHC is a clinically and genetically heterogeneous disorder, with one well-defined clinical syndrome mapping to chromosome 14q. C1 Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. Erasmus Univ, Dept Pediat Neurol, NL-3000 DR Rotterdam, Netherlands. Univ Alabama, Div Pediat Neurol, Birmingham, AL USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Univ Athens, Sch Med, Dept Neurol, GR-11527 Athens, Greece. Univ Utrecht, Ctr Med, Div Med Genet, Utrecht, Netherlands. Univ Nijmegen, Ctr Med, Dept Human Genet, Nijmegen, Netherlands. RP Arts, WFM (reprint author), Erasmus MC Sophia Childrens Hosp, Dept Pediat Neurol, POB 2600, NL-3000 CB Rotterdam, Netherlands. RI Dure, Leon/B-3243-2008 NR 30 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 27 PY 2002 VL 59 IS 4 BP 579 EP 584 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 586YJ UT WOS:000177613500019 PM 12196653 ER PT J AU Yoshii, A Krishnamoorthy, KS Grant, PE AF Yoshii, A Krishnamoorthy, KS Grant, PE TI Abnormal cortical development shown by 3D MRI in Prader-Willi syndrome SO NEUROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Pediat Neurol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol, Boston, MA 02114 USA. RP Grant, PE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Gray 2,Room B285,55 Fruit St, Boston, MA 02114 USA. NR 4 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 27 PY 2002 VL 59 IS 4 BP 644 EP 645 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 586YJ UT WOS:000177613500038 PM 12196672 ER PT J AU Kunisaki, SM Haller, GW Shimizu, A Kitamura, H Colvin, RB Sachs, DH AF Kunisaki, SM Haller, GW Shimizu, A Kitamura, H Colvin, RB Sachs, DH TI Autologous graft-versus-host disease in a porcine bone marrow transplant model SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; STEM-CELL TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; CLASS-II GENES; MINIATURE SWINE; T-CELLS; BREAST-CANCER; CYCLOSPORIN-A; LETHAL GRAFT; TREATED RATS AB Background. Autologous graft-versus-host disease (autoGvHD) has been reported in patients and can be induced in rodents by syngeneic bone marrow transplantation (BMT) and a brief administration of cyclosporine A (CsA). To our knowledge, there is no previous large-animal model for this phenomenon, nor is there a model in which autoGvHD occurs spontaneously after autologous bone marrow transplant (autoBMT) in the absence of CsA induction. During our studies of autoBMT in miniature swine, performed without CsA treatment, we noted the frequent occurrence of a rash consistent with autoGvHD. We hypothesized that the extent of peripheral blood contamination of the bone marrow (BM) inoculum before transplant may have correlated with the incidence of such autoGvHD. Methods. Retrospective analysis of the prevalence of autoGvHD in swine was carried out in all animals that had become engrafted after autoBMT in our laboratory. Subsequent prospective experiments attempted to induce autoGvHD by transplanting autologous BM enriched with autologous peripheral blood into lethally irradiated animals. Results. Our data showed that autoGvHD frequently occurs in swine after autoBMT, with the most severe cases of the disease occurring in animals with the highest levels of peripheral blood contamination of the BM inoculum. Furthermore, mixed lymphocyte reactions (MLR) against self antigens were positive only in animals affected by autoGvHD. Conclusion. These findings provide the first evidence for autoGvHD without the use of CsA in a preclinical BMT model. The role of autologous T cells needs further delineation but may help to explain the occasional occurrences of autoGvHD that have been reported in humans after autoBMT. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Surg HST, Boston, MA 02129 USA. Univ Klinikum Mannheim, Chirurg Klin, Klinikum Mannheim GMBH, Mannheim, Germany. Nippon Med Coll, Dept Pathol, Tokyo 113, Japan. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Surg HST, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [1R01 CA79988]; NHLBI NIH HHS [5R01 HL63430] NR 54 TC 0 Z9 0 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 AUG 27 PY 2002 VL 74 IS 4 BP 465 EP 471 DI 10.1097/01.TP.0000026254.49423.D7 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 590FV UT WOS:000177808600006 PM 12352903 ER PT J AU Adams, PL Cohen, DJ Danovitch, GM Edington, RMD Gaston, RS Jacobs, CL Luskin, RS Metzger, RA Peters, TG Siminoff, LA Veatch, RM Rothberg-Wegman, L Bartlett, ST Brigham, L Burdick, J Gunderson, S Harmon, W Matas, AJ Thistlethwaite, JR Delmonico, FL AF Adams, PL Cohen, DJ Danovitch, GM Edington, RMD Gaston, RS Jacobs, CL Luskin, RS Metzger, RA Peters, TG Siminoff, LA Veatch, RM Rothberg-Wegman, L Bartlett, ST Brigham, L Burdick, J Gunderson, S Harmon, W Matas, AJ Thistlethwaite, JR Delmonico, FL TI The nondirected live-kidney donor: Ethical considerations and practice guidelines - A national conference report SO TRANSPLANTATION LA English DT Article ID DONATION AB Background. The success of kidney transplantation from a genetically unrelated living spouse or friend has influenced transplant physicians to consider the requests of individuals wishing to volunteer to be a kidney donor who have no intended recipient specified. Representatives of the transplant community gathered in Boston, MA, on May 31, 2001, to deliberate on the experience of live kidney donation from such volunteers, currently termed nondirected donors (NDD). Objective of Conference Participants. The objective of the conference was to recommend ethical and practice guidelines for health care professionals considering the transplantation of a kidney from a live NDD. Conference Participants. This conference was convened under the sponsorship of The National Kidney Foundation, with representation from The American Society of Transplantation and The American Society of Transplant Surgeons, The American Society of Nephrology, The United Resource Networks, The United Network for Organ Sharing, The Association of Organ Procurement Organizations, The National Institutes of Health, and The Division of Transplantation of the Health Resources and Services Administration (see Appendix). Conference Report. The suggested content of screening interviews, which provide information regarding the donation process, elicits pertinent medical and psychosocial history, and assesses NDD motivation are presented in this report. Approaches to identifying the center that would evaluate the suitability of the NDD, to performing the kidney recovery, and to selecting the NDD recipient are also proposed. Other ethical issues such as the use of prisoners as an NDD, compensation for the NDD, media involvement, and communication between the NDD and recipient are discussed. Conclusion. The willingness of health care professionals to consider NDD volunteers is driven by the compelling need to provide organs for an ever-expanding list of patients awaiting a kidney transplant. However, the psychological impact and emotional reward of donation has yet to be determined for NDD who may not have any relationship to the recipient or knowledge of the recipient's outcome. Transplant centers that accept NDD should document an informed consent process that details donor risks, assures donor safety, and determines that the goals and expectations of the NDD and the recipient can be realized. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RI Siminoff, Laura /H-6277-2012 NR 13 TC 81 Z9 84 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2002 VL 74 IS 4 BP 582 EP 589 AR UNSP 0041-1337/02/7404-582/0 DI 10.1097/00007890-200208270-00030 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 590FV UT WOS:000177808600030 PM 12352927 ER PT J AU Pham, T Guerrini, S Wong, H Reeve, J Sternini, C AF Pham, T Guerrini, S Wong, H Reeve, J Sternini, C TI Distribution of galanin receptor 1 - Immunoreactivity in the rat stomach and small intestine SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE enteric neurons; excitatory neurons; inhibitory neurons; enterochromaffin-like cells; interstitial cells of Cajal; gastrointestinal motility ID ENTEROCHROMAFFIN-LIKE CELLS; SMOOTH-MUSCLE CELLS; PIG SMALL-INTESTINE; GUINEA-PIG; GASTROINTESTINAL-TRACT; INTERSTITIAL-CELLS; PHARMACOLOGICAL CHARACTERIZATION; CONTAINING NEURONS; MOLECULAR-CLONING; ENTERIC NEURONS AB Galanin affects gastrointestinal functions by activating different G protein-coupled receptors. Here, we identified the sites of expression of the galanin receptor 1 (GAL-R1) subtype in the rat stomach and small intestine by using immunohistochemistry with an antibody raised to the third intracellular loop of rat GAL-R1 (GAL-R1(Y225-238)) and confocal microscopy. Antibody specificity was confirmed by (1) the detection of a band at approximately 70 kDa in Western blot of membranes from GAL-R1 transfected cells, (2) the cell surface staining of GAL-R1 transfected cells, which was not detected in control cells, and (3) the abolition of Western signal and tissue immunostaining by preadsorbing the antibody with the peptide used for immunization. GAL-R1 immunoreactivity was localized to the cell surface of enterochromaffin-like cells, and of myenteric and submucous neurons, and to fibers distributed to the plexuses, interconnecting strands, muscle layers, vasculature, and mucosa. A dense network of GAL-R1 immunoreactivity was observed in the deep muscular plexus in very close association with interstitial cells of Cajal visualized by c-kit immunostaining. In the ileum, 81.6% of GAL-R1 myenteric neurons and 70.7% of GAL-R1 submucosal neurons were substance P immunoreactive. Vasoactive intestinal polypeptide immunoreactivity was found in 48.3% of GAL-R1 submucosal neurons, but not in GAL-R1 myenteric neurons. These findings support the hypothesis that GAL-R1 mediates galanin actions on gastrointestinal motility and secretion by modulating the release of other neurotransmitters and contributes to galanin-induced inhibition of gastric acid secretion by means of the suppression of endogenous histamine release. (C) 2002 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Div Digest Dis, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Sternini, C (reprint author), Univ Calif Los Angeles, Div Digest Dis, Digest Dis Res Ctr, CURE, Bldg 115,Room 224,VAGLAHS,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK41301, DK35740, DK57073] NR 49 TC 36 Z9 37 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 26 PY 2002 VL 450 IS 3 BP 292 EP 302 DI 10.1002/cne.10311 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 577UQ UT WOS:000177080900007 PM 12209857 ER PT J AU Tapon, N Harvey, KF Bell, DW Wahrer, DCR Schiripo, TA Haber, DA Hariharan, IK AF Tapon, N Harvey, KF Bell, DW Wahrer, DCR Schiripo, TA Haber, DA Hariharan, IK TI salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines SO CELL LA English DT Article ID DEPENDENT KINASE INHIBITOR; GENE; HID; PROLIFERATION; EMBRYOGENESIS; SURVIVAL; GROWTH; EXPRESSION; HOMOLOGS; ENCODES AB The number of cells in an organism is determined by regulating both cell proliferation and cell death. Relatively few mechanisms have been identified that can modulate both of these processes. In a screen for Drosophila mutations that result in tissue overgrowth, we identified salvador (sav), a gene that promotes both cell cycle exit and cell death. Elevated Cyclin E and DIAP1 levels are found in mutant cells, resulting in delayed cell cycle exit and impaired apoptosis. Salvador contains two WW domains and binds to the Warts (or LATS) protein kinase. The human ortholog of salvador(hWW45) is mutated in three cancer cell lines. Thus, salvador restricts cell numbers in vivo by functioning as a dual regulator of cell proliferation and apoptosis. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA87691]; NEI NIH HHS [EY11632]; NIGMS NIH HHS [GM61672] NR 29 TC 413 Z9 430 U1 6 U2 40 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 23 PY 2002 VL 110 IS 4 BP 467 EP 478 DI 10.1016/S0092-8674(02)00824-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 587QJ UT WOS:000177653200008 PM 12202036 ER PT J AU Shim, EY Walker, AK Blackwell, TK AF Shim, EY Walker, AK Blackwell, TK TI Broad requirement for the mediator subunit RGR-1 for transcription in the Caenorhabditis elegans embryo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; LAEVIS EARLY EMBRYOS; C-ELEGANS; YEAST; HOLOENZYME; ACTIVATION; COMPLEXES; SIN4; PHOSPHORYLATION; ORGANIZATION AB The Mediator-related transcription co-factors integrate positive and negative inputs and recruit and activate the RNA polymerase II complex. To understand the role of Mediator during transcription, it is important to identify Mediator subunits that are essential for its functions. In the yeast Mediator, the conserved component Rgr1 is associated with multiple subunits that are required for specific activation or repression events. Yeast rgr1 is essential for viability, for certain repression mechanisms, and for activation of heat shock genes, but it is not known whether rgr1 is generally important for transcription. Here we have performed the first analysis of rgr-1 function in a metazoan. We found that in the developing Caenorhabditis elegans embryo rgr-1 is broadly required for transcription and for phosphorylation of both Ser-2 and Ser-5 of the RNA polymerase II C-terminal domain repeat. We conclude that RGR-1 fulfills a critical Mediator function that is broadly essential for metazoan mRNA transcription and that RGR-1 may be required at an early recruitment or initiation step. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM 62891, R01 GM062891] NR 36 TC 16 Z9 25 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 AUG 23 PY 2002 VL 277 IS 34 BP 30413 EP 30416 DI 10.1074/jbc.C200305200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 586JA UT WOS:000177579800002 PM 12089139 ER PT J AU Lin, AE Grossfeld, PD Hamilton, RM Smoot, L Gripp, KW Proud, V Weksberg, R Wheeler, P Picker, J Irons, M Zackai, E Marino, B Scott, CI Nicholson, L AF Lin, AE Grossfeld, PD Hamilton, RM Smoot, L Gripp, KW Proud, V Weksberg, R Wheeler, P Picker, J Irons, M Zackai, E Marino, B Scott, CI Nicholson, L TI Further delineation of cardiac abnormalities in Costello syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE atrial tachycardia; cardiovascular malformation; chaotic atrial rhythm; conge-nital heart defect; Costello syndrome; hypertrophic cardiomyopathy; MCA/MR syndrome; multifocal atrial tachycardia ID CUTANEOUS-SKELETAL SYNDROME; CHAOTIC ATRIAL RHYTHM; NATURAL-HISTORY; CUTIS LAXA; DIFFERENTIAL-DIAGNOSIS; RETARDATION SYNDROME; BLADDER-CARCINOMA; NOONAN-SYNDROME; CHILDREN; PATIENT AB We review the cardiac abnormalities in 94 patients (27 new, 67 literature) with Costello syndrome, an increasingly recognized syndrome consisting of increased birth weight, postnatal growth retardation, and distinctive facial, skin, and musculoskeletal features (MIM 218040). A cardiac abnormality was found in 59 (63%) patients, with each of three categories occurring in approximately one-third of patients. A cardiovascular malformation (CVM) was noted in 30%, typically pulmonic stenosis (46% of those with a CVM). Cardiac hypertrophy was reported in 34%, which involved the left ventricle in 50% and was usually consistent with classic hypertrophic cardiomyopathy (HCM). A variety of rhythm disturbances were reported in 33%. Most (74%) were atrial tachycardia that was reported as supraventricular, chaotic, multifocal, or ectopic. Of 31 patients with a rhythm abnormality, 22 (68%) had an additional abnormality, i.e., CVM (4), cardiac hypertrophy (12), or both (6). Nine patients had isolated dysrhythmia, five (56%) of whom died. All of the 12 (13%) patients who died had a cardiac abnormality. One patient died of embryonal rhabdomyosarcoma, but in the remainder, a cardiac cause of death could not be disproved. All patients with Costello syndrome need a baseline cardiology evaluation with echocardiography and Holter monitoring. Additional prospective evaluations, even in patients without apparent cardiac abnormalities, would be prudent, although data are insufficient to propose a specific schedule. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Hosp Sick Children, Div Cardiol, Toronto, ON M5G 1X8, Canada. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Hosp Kings Daughters, Dept Pediat, Div Med Genet, Norfolk, VA USA. Hosp Sick Children, Div Clin & Med Genet, Toronto, ON M5G 1X8, Canada. Tufts Univ New England Med Ctr, Dept Pediat, Div Genet, Boston, MA 02111 USA. Childrens Hosp, Dept Genet, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. AI DuPont Hosp Children, Div Med Genet, Wilmington, DE USA. RP Lin, AE (reprint author), Brigham & Womens Hosp, Teratol Program, 75 Francis St,Old PBBH B501, Boston, MA 02115 USA. NR 87 TC 55 Z9 59 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 22 PY 2002 VL 111 IS 2 BP 115 EP 129 DI 10.1002/ajmg.10558 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 578HM UT WOS:000177111400001 PM 12210337 ER PT J AU Huang, TS Korson, MS Krauss, C Holmes, LB AF Huang, TS Korson, MS Krauss, C Holmes, LB TI Four cases with hypoplastic thumbs and encephaloceles SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE triphalangeal thumbs; encephalocele; rib anomaly ID TRIPHALANGEAL THUMB; HEDGEHOG; GENE; MAPS; MALFORMATIONS; EXPRESSION; 7Q36 AB We report on four infants with hypoplastic thumbs and occipital encephaloceles. None had either a chromosome abnormality or a family history of any major malformation. The literature and database were searched intensively. No similar cases were reported previously, suggesting that the constellations might represent a new genetic syndrome. (C) 2002 Wiley-Liss, Inc. C1 Childrens Hosp, Div Genet & Metab, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Div Genet & Metab, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Serv Pediat,Genet & Teratol Unit, Boston, MA USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA USA. RP Huang, TS (reprint author), Univ Calif Irvine, Dept Pediat, Room C202, Irvine, CA 92697 USA. FU NCRR NIH HHS [M01RR02172] NR 15 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 22 PY 2002 VL 111 IS 2 BP 178 EP 181 DI 10.1002/ajmg.10439 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 578HM UT WOS:000177111400010 PM 12210346 ER PT J AU MacGillivray, TE Vlahakes, GJ AF MacGillivray, TE Vlahakes, GJ TI Perspective - Angioplasty versus minimally invasive bypass surgery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP MacGillivray, TE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 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 AUG 22 PY 2002 VL 347 IS 8 BP 551 EP 552 DI 10.1056/NEJMp020078 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 587ZR UT WOS:000177675400001 PM 12192012 ER PT J AU Berger, DL Davis, PC Mark, EJ Mohammadkhani, M Colvin, RB AF Berger, DL Davis, PC Mark, EJ Mohammadkhani, M Colvin, RB TI An 87-year-old woman with abdominal pain, vomiting, bloody diarrhea, and an abdominal mass - Ileocecal intussusception due to colonic adenocarcinoma arising in a large villous adenoma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ADULT INTUSSUSCEPTION; MANAGEMENT C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 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 AUG 22 PY 2002 VL 347 IS 8 BP 601 EP 606 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 587ZR UT WOS:000177675400010 ER PT J AU Mitsiades, CS Mitsiades, N Poulaki, V Schlossman, R Akiyama, M Chauhan, D Hideshima, T Treon, SP Munshi, NC Richardson, PG Anderson, KC AF Mitsiades, CS Mitsiades, N Poulaki, V Schlossman, R Akiyama, M Chauhan, D Hideshima, T Treon, SP Munshi, NC Richardson, PG Anderson, KC TI Activation of NF-kappa B and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications SO ONCOGENE LA English DT Article DE multiple myeloma; IGF-1; NF-kappa B; IAPs; Apo2L; TRAIL ID GROWTH-FACTOR-I; DEXAMETHASONE-INDUCED APOPTOSIS; NECROSIS-FACTOR-ALPHA; PROSTATE-CANCER; NUCLEAR TRANSLOCATION; MEDIATED APOPTOSIS; RAT STRIATUM; TNF-ALPHA; INDUCTION; EXPRESSION AB Interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) promote the proliferation of multiple myeloma (MM) cells and protect them against dexamethasone (Dex)-induced apoptosis. We have previously shown that Apo2 ligand/TNF-Related apoptosis inducing ligand (Apo2L/TRAIL) induces apoptosis of MM cells, including cells either sensitive or resistant to Dex and cytotoxic drugs, and overcomes the growth and survival effect of IL-6; conversely, NF-kappaB transcriptional activity attenuates their Apo2L/TRAIL-sensitivity. In the current study, we demonstrate that IGF-1 stimulates sustained activation of NF-kappaB and Akt; induces phosphorylation of the FKHRL-1 Forkhead transcription factor; upregulates a series of intracellular anti-apoptotic proteins including FLIP, survivin, cIAP-2, A1/Bfl-1, and XIAP; and decreases Apo2L/TRAIL-sensitivity of MM cells. In contrast, IL-6 does not cause sustained NF-kappaB activation, induces less pronounced Akt activation and FKHRL-1 phosphorylation than IGF-1, and increases the expression of only survivin. Forced overexpression of constitutively active Akt in MM-1S cells reduced their sensitivity to Apo2L/TRAIL and to doxorubicin (Doxo). In contrast, the Akt inhibitor IL-6-Hydroxymethylchiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate induced cell death of both Dex- and Doxo-sensitive and -resistant cells; opposed the protective effect of constitutive Akt activity against Apo2L/TRAIL; and abrogated the NF-kappaB activation, increase of anti-apoptotic proteins and protection against Apo2L/TRAIL induced by IGF-1. These findings therefore define an important role of the Akt pathway in modulating tumor cell responsiveness to Apo2L/TRAIL, delineate molecular mechanisms for the survival effects of IGF-1, and characterize differential pathophysiologic sequelae of IGF-1 vs IL-6 on MM cells. Importantly, they provide the basis for future clinical trials in MM combining conventional or novel agents with strategies designed to neutralize IGF-1. C1 Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Anderson, KC (reprint author), Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378, R0-1 50947] NR 44 TC 354 Z9 366 U1 3 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 22 PY 2002 VL 21 IS 37 BP 5673 EP 5683 DI 10.1038/sj.onc.1205664 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 584JL UT WOS:000177463400002 PM 12173037 ER PT J AU Mehta, RH O'Gara, PT Bossone, E Nienaber, CA Myrmel, T Cooper, JV Smith, DE Armstrong, WF Isselbacher, EM Pape, LA Eagle, KA Gilon, D AF Mehta, RH O'Gara, PT Bossone, E Nienaber, CA Myrmel, T Cooper, JV Smith, DE Armstrong, WF Isselbacher, EM Pape, LA Eagle, KA Gilon, D CA Int Registry Acute Aortic Dissecti TI Acute type A aortic dissection in the elderly: Clinical characteristics, management, and outcomes in the current era SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-College-of-Cardiology CY MAR, 2001 CL ORLANDO, FLORIDA SP Amer Coll Cardiol ID ACUTE MYOCARDIAL-INFARCTION; AGE; SEPTUAGENARIANS; OCTOGENARIANS; FENESTRATION; MORTALITY; VALVE; OLDER AB OBJECTIVES We sought to evaluate the clinical characteristics, management, and outcomes of elderly patients with acute type A aortic dissection. BACKGROUND Few data exist on the clinical manifestations and outcomes of acute type A aortic dissection in an elderly patient cohort. METHODS We categorized 550 patients with type A aortic dissection enrolled in the International Registry of Acute Aortic Dissection into two age strata (<70 and greater than or equal to70 years) and compared their clinical features, management, and in-hospital events. RESULTS Thirty-two percent of patients with type A dissection were-aged greater than or equal to70 years. Marfan syndrome was exclusively associated with dissection in the young, whereas hypertension, atherosclerosis and iatrogenic dissection predominated in older patients. Typical symptoms (abrupt onset of chest or back pain) and signs (aortic regurgitation murmur or pulse deficits) of dissection were less common among the elderly. Fewer elderly patients were managed surgically than younger patients (64% vs. 86%, p < 0.0001). Hypotension occurred more frequently (46% vs. 32%, p = 0.002) and focal neurologic deficits less frequently (18% vs. 26%, p = 0.04) among the elderly. In-hospital mortality was higher among older patients (43% vs. 28%, p = 0.0006). Logistic regression analysis identified age greater than or equal to70 years as an independent predictor of hospital death for acute type A aortic dissection (odds ratio 1.7, 95% confidence interval 1.1-2.8; p 0.03). CONCLUSIONS Our study shows significant differences between older (age greater than or equal to70 years) and younger (age <70 years) patients with acute type A aortic dissection in their clinical characteristics, management, and hospital outcomes. Future research should evaluate strategies to improve outcomes in this high-risk elderly cohort. (C) 2002 by the American College of Cardiology Foundation. C1 Univ Michigan, Ann Arbor, MI 48105 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Ist Policlin San Donato, San Donato Milanese, Italy. Univ Rostock, Rostock, Germany. Univ Tromso Hosp, N-9012 Tromso, Norway. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts Hosp, Worcester, MA USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. RP Mehta, RH (reprint author), Univ Michigan, Cardiol 111A 7E,2215 Fuller Rd, Ann Arbor, MI 48105 USA. NR 21 TC 136 Z9 147 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 21 PY 2002 VL 40 IS 4 BP 685 EP 692 AR PII S0735-1097(02)02005-3 DI 10.1016/S0735-1097(02)02005-3 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 584NP UT WOS:000177474000012 PM 12204498 ER PT J AU Barr, RG Nathan, DM Meigs, JB Singer, DE AF Barr, RG Nathan, DM Meigs, JB Singer, DE TI Tests of glycemia for the diagnosis of type 2 diabetes mellitus SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; GLYCOSYLATED HEMOGLOBIN LEVELS; HEALTH-ORGANIZATION CRITERIA; FASTING PLASMA-GLUCOSE; CORONARY HEART-DISEASE; FOLLOW-UP; CARDIOVASCULAR-DISEASE; GLYCATED HEMOGLOBIN; PIMA-INDIANS; RISK-FACTORS AB This paper discusses tests of glycemia for the diagnosis of type 2 diabetes mellitus, with particular reference to the 1997 diagnostic criteria of the American Diabetes Association. The potential benefits of the lower diagnostic threshold for fasting plasma glucose are not well defined. However, the change in the diagnostic cutoff for diabetes mellitus affects as many as 1.9 million persons in the United States; therefore, the medical and social costs of the lower threshold may be considerable. Type 2 diabetes mellitus is defined by a threshold imposed on the continuous distribution of glycemic levels, typically with respect to risk for microvascular complications. However, the burden of type 2 diabetes relates more to macrovascular than microvascular complications. Because no clear threshold exists for macrovascular complications, a formal balancing of direct and indirect costs with both microvascular and macrovascular complications may be appropriate to establish glycemic thresholds. Because fasting plasma glucose, hemoglobin A(1c), and the oral glucose tolerance test all predict diabetic complications yet test reliability is better for fasting plasma glucose and hemoglobin A,c than for the oral glucose tolerance test, we suggest an alternative diagnostic approach: If random plasma glucose is elevated (greater than or equal to11.1 mmol/L [200 mg/dL]) and the hemoglobin A,c level is more than 2 SDs above the laboratory mean, then diabetes mellitus should be diagnosed, and management should be based on the hemoglobin A,c level. If the result of only one of these tests is positive, then fasting plasma glucose should be tested to evaluate the patient for impaired fasting glucose and diabetes mellitus. The glycemic threshold for type 2 diabetes should be established by cost-effectiveness analysis. The clinical diagnosis of diabetes mellitus could be streamlined by incorporation of hemoglobin A,c into established criteria. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Barr, RG (reprint author), Columbia Presbyterian Med Ctr, Div Gen Med, PH-9 E 105,622 W 168th St, New York, NY 10032 USA. FU BHP HRSA HHS [PE-11001] NR 112 TC 100 Z9 106 U1 0 U2 4 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 AUG 20 PY 2002 VL 137 IS 4 BP 263 EP 272 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 585BB UT WOS:000177502300007 PM 12186517 ER PT J AU Mathis, D King, GL AF Mathis, D King, GL TI B-cell signaling: Protein kinase C delta puts the brakes on SO CURRENT BIOLOGY LA English DT Editorial Material ID REACTIVE LYMPHOCYTES-B; CD4(+) T-CELLS; TRANSCRIPTION FACTORS; TRANSDUCTION; ACTIVATION; RECEPTOR; MICE AB The phenotype of mice lacking the delta isoform of protein kinase C reveals that this isoform curtails signaling events after engagement of the antigen-specific receptor on B cells. The result is a state of non-responsiveness, termed anergy, that represents one form of immunological self-tolerance. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Boston, MA 02215 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 20 PY 2002 VL 12 IS 16 BP R554 EP R556 AR PII S0960-9822(02)01052-7 DI 10.1016/S0960-9822(02)01052-7 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 586HF UT WOS:000177578000008 PM 12194836 ER PT J AU Gasca, S Canizares, J Santa Barbara, P Mejean, C Poulat, F Berta, P Boizet-Bonhoure, B AF Gasca, S Canizares, J Santa Barbara, P Mejean, C Poulat, F Berta, P Boizet-Bonhoure, B TI A nuclear export signal within the high mobility group domain regulates the nucleocytoplasmic translocation of SOX9 during sexual determination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTI-MULLERIAN HORMONE; SRY-RELATED GENE; KAPPA-B-ALPHA; SUBCELLULAR-LOCALIZATION; CYTOPLASMIC LOCALIZATION; CAMPOMELIC DYSPLASIA; DETERMINING REGION; CELL-MIGRATION; PROTEIN; MOUSE AB In mammals, male sex determination starts when the Y chromosome Sry gene is expressed within the undetermined male gonad. One of the earliest effect of Sry expression is to induce up-regulation of Sox9 gene expression in the developing gonad. SOX9, like SRY, contains a high mobility group domain and is sufficient to induce testis differentiation in transgenic XX mice. Before sexual differentiation, SOX9 protein is initially found in the cytoplasm of undifferentiated gonads from both sexes. At the time of testis differentiation and anti-Mullerian hormone expression, it becomes localized to the nuclear compartment in males whereas it is down-regulated in females. in this report, we used NIH 3T3 cells as a model to examine the regulation of SOX9 nucleo-cytoplasmic shuttling. SOX9-transfected cells expressed nuclear and cytoplasmic SOX9 whereas transfected cells treated with the nuclear export inhibitor leptomycin B, displayed an exclusive nuclear localization of SOX9. By using SOX9 deletion constructs in green fluorescent protein fusion proteins, we identified a functional nuclear export signal sequence between amino acids 134 and 147 of SOX9 high mobility group box. More strikingly, we show that inhibiting nuclear export with leptomycin B in mouse XX gonads cultured in vitro induced a sex reversal phenotype characterized by nuclear SOX9 and anti-Mullerian hormone expression. These results indicate that SOX9 nuclear export signal is essential for SOX9 sex-specific subcellular localization and could be part of a regulatory switch repressing (in females) or triggering (in males) male-specific sexual differentiation. C1 Inst Genet Humaine, CNRS UPR 1142, Human Mol Genet Grp, F-34396 Montpellier 5, France. Massachusetts Gen Hosp, Dept Pediat Surg Res, Boston, MA 02114 USA. RP Berta, P (reprint author), Inst Genet Humaine, CNRS UPR 1142, Human Mol Genet Grp, F-34396 Montpellier 5, France. EM berta@igh.cnrs.fr RI Canizares, Joaquin/M-3255-2014 OI Canizares, Joaquin/0000-0001-9002-5516 NR 46 TC 93 Z9 94 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 20 PY 2002 VL 99 IS 17 BP 11199 EP 11204 DI 10.1073/pnas.172383099 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586VM UT WOS:000177606900046 PM 12169669 ER PT J AU Boon, K Osorio, EC Greenhut, SF Schaefer, CF Shoemaker, J Polyak, K Morin, PJ Buetow, KH Strausberg, RL de Souza, SJ Riggins, GJ AF Boon, K Osorio, EC Greenhut, SF Schaefer, CF Shoemaker, J Polyak, K Morin, PJ Buetow, KH Strausberg, RL de Souza, SJ Riggins, GJ TI An anatomy of normal and malignant gene expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SERIAL ANALYSIS; CANCER; PROJECT; GENOME AB A gene's expression pattern provides clues to its role in normal physiology and disease. To provide quantitative expression levels on a genome-wide scale, the Cancer Genome Anatomy Project (CGAP) uses serial analysis of gene expression (SAGE). Over 5 million transcript tags from more than 100 human cell types have been assembled. To enhance the utility of this data, the CGAP SAGE project created SAGE Genie, a web site for the analysis and presentation of SAGE data (http://cgap.nci.nih.gov/SAGE). SAGE Genie provides an automatic link between gene names and SAGE transcript levels, accounting for alternative transcription and many potential errors. These informatics advances provide a rapid and intuitive view of transcript expression in the human body or brain, displayed on the SAGE Anatomic Viewer. We report here an easily accessible view of nearly any gene's expression in a wide variety of malignant and normal tissues. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. NIA, Biol Chem Lab, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Off Canc Genomics, Bethesda, MD 20892 USA. NCI, Ctr Bioinformat, Bethesda, MD 20892 USA. Ludwig Inst Canc Res, BR-01509010 Sao Paulo, Brazil. RP Riggins, GJ (reprint author), Duke Univ, Med Ctr, Durham, NC 27710 USA. FU NCI NIH HHS [U01 CA088128, U01 CA88128] NR 16 TC 229 Z9 242 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 20 PY 2002 VL 99 IS 17 BP 11287 EP 11292 DI 10.1073/pnas.152324199 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586VM UT WOS:000177606900062 PM 12119410 ER PT J AU Orange, JS Ramesh, N Remold-O'Donnell, E Sasahara, Y Koopman, L Byrne, M Bonilla, FA Rosen, FS Geha, RS Strominger, JL AF Orange, JS Ramesh, N Remold-O'Donnell, E Sasahara, Y Koopman, L Byrne, M Bonilla, FA Rosen, FS Geha, RS Strominger, JL TI Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NATURAL-KILLER-CELLS; T-CELLS; PRIMARY IMMUNODEFICIENCIES; HERPESVIRUS INFECTIONS; IMMUNE SYNAPSE; POLARIZATION; CYTOSKELETON; LYMPHOCYTES; CHILDHOOD; SIMPLEX AB The Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder caused by a mutation in WAS protein (WASp) that results in defective actin polymerization. Although the function of many hematopoietic cells requires WASp, the specific expression and function of this molecule in natural killer (NK) cells is unknown. Here, we report that WAS patients have increased percentages of peripheral blood NK cells and that fresh enriched NK cells from two patients with a WASp mutation have defective cytolytic function. In normal NK cells, WASp was expressed and localized to the activating immunologic synapse (IS) with filamentous actin (F-actin). Perforin also localized to the NK cell-activating IS but at a lesser frequency than F-actin and WASp. The accumulation of F-actin and WASp at the activating IS was decreased significantly in NK cells that had been treated with the inhibitor of actin polymerization, cytochalasin D. NK cells from WAS patients lacked expression of WASp and accumulated F-actin at the activating IS infrequently. Thus, WASp has an important function in NK cells. In patients with WASp mutations, the resulting NK cell defects are likely to contribute to their disease. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Orange, JS (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 7 Divin Ave, Cambridge, MA 02138 USA. RI Orange, Jordan/D-5239-2009; OI orange, jordan/0000-0001-7117-7725 FU NHLBI NIH HHS [HL-59561, P01 HL059561]; NIAID NIH HHS [AI-50207, R01 AI050207, T32 AI007512, AI-07512] NR 32 TC 146 Z9 150 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 AUG 20 PY 2002 VL 99 IS 17 BP 11351 EP 11356 DI 10.1073/pnas.162376099 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586VM UT WOS:000177606900073 PM 12177428 ER PT J AU Shenton, ME Gerig, G McCarley, RW Szekely, G Kikinis, R AF Shenton, ME Gerig, G McCarley, RW Szekely, G Kikinis, R TI Amygdala-hippocampal shape differences in schizophrenia: the application of 3D shape models to volumetric MR data SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Review DE schizophrenia; magnetic resonance imaging (MRI); amygdala-hippocampal complex; hippocampus; neurodevelopmental abnormalities; shape deformations; shape analysis; three-dimensional (3D) shape techniques; shape descriptors ID CAVUM SEPTI PELLUCIDI; PLANUM TEMPORALE ASYMMETRY; NUCLEAR MAGNETIC-RESONANCE; ZOOM-INVARIANT VISION; HUMAN CEREBRAL-CORTEX; PR-AE-COX; AFFECTIVE-DISORDER; THOUGHT-DISORDER; BRAIN MORPHOLOGY; MEDICAL IMAGES AB Evidence suggests that sonic structural brain abnormalities in schizophrenia are neurodevelopmental in origin. There is also growing evidence to suggest that shape deformations in brain structure may reflect abnormalities in neurodevelopment. While many magnetic resonance (MR) imaging studies have investigated brain area and volume measures in schizophrenia, fewer have focused on shape deformations. In this MR study we used a 3D shape representation technique, based on spherical harmonic functions, to analyze left and right amygdala-hippocampus shapes in each of 15 patients with schizophrenia and 15 healthy controls matched for age, gender, handedness and parental socioeconomic status. Left/right asymmetry was also measured for both shape and volume differences. Additionally, shape and Volume measurements were combined in a composite analysis. There were no differences between groups in overall volume or shape. Left/right amygdala-hippocampal asymmetry, however, was significantly larger in patients than controls for both relative volume and shape. The local brain regions responsible for the left/ right asymmetry differences in patients with schizophrenia were in the tail of the hippocampus (including both the inferior aspect adjacent to parahippocampal gyrus and the superior aspect adjacent to the lateral geniculate nucleus and more anteriorly to the cerebral peduncles) and in portions of the amygdala body (including the anterior-superior aspect adjacent to the basal nucleus), Also, in patients, increased volumetric asymmetry tended to be correlated with increased left/right shape asymmetry. Furthermore, a combined analysis of volume and shape asymmetry resulted in improved differentiation between groups. Classification function analyses correctly classified 70%, of cases using volume, 73.3% using shape, and 87% using combined volume and shape measures. These findings suggest that shape provides important new information toward characterizing the pathophysiology of schizophrenia, and that combining volume and shape measures provides improved group discrimination in studies investigating brain abnormalities in schizophrenia. An evaluation of shape deformations also suggests local abnormalities in the amygdala-hippocampal complex in schizophrenia. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst,Brockton Div, Dept Psychiat 116A,Lab Neurosci,Clin Neurosci Di, Brockton, MA 02301 USA. Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Swiss Fed Inst Technol, Swiss Fed Inst Technol, Commun Technol Lab, Zurich, Switzerland. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Radiol, MRI Div,Surg Planning Lab, Boston, MA 02115 USA. RP Shenton, ME (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst,Brockton Div, Dept Psychiat 116A,Lab Neurosci,Clin Neurosci Di, 940 Belmont St, Brockton, MA 02301 USA. EM martha_shenton@hms.harvard.edu RI Szekely, Gabor/A-3880-2008; Rohlf, F/A-8710-2008; McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NCI NIH HHS [P01 CA067165, P01 CA67165]; NCRR NIH HHS [P41 RR013218, P41 RR13218, R01 RR11747]; NIA NIH HHS [P01 AG004953, P01 AG04953]; NIMH NIH HHS [K02 MH001110, K02 MH-01110, K02 MH001110-10, R01 MH-50747, R01 MH050740, R01 MH050740-15]; PHS HHS [R01-40977] NR 108 TC 80 Z9 82 U1 4 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG 20 PY 2002 VL 115 IS 1-2 BP 15 EP 35 AR PII S0925-4927(02)00025-2 DI 10.1016/S0925-4927(02)00025-2 PG 21 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 589JB UT WOS:000177754200002 PM 12165365 ER PT J AU LaBonte, JA Babcock, GJ Patel, T Sodroski, J AF LaBonte, JA Babcock, GJ Patel, T Sodroski, J TI Blockade of HIV-1 infection of new world monkey cells occurs primarily at the stage of virus entry SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE human immunodeficiency virus; species restrictions; New World monkeys; receptors; virus entry ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; T-LYMPHOTROPIC RETROVIRUS; AIDS-LIKE DISEASE; CHEMOKINE RECEPTORS; CYCLOPHILIN-A; HUMAN CD4; HUMAN-LYMPHOCYTES; TYPE-1 INFECTION; RHESUS-MONKEYS AB HIV-1 naturally infects chimpanzees and humans, but does not infect Old World monkeys because of replication blocks that occur after virus entry into the cell. To understand the species-specific restrictions Operating Oil HIV-1 infection, the ability of HIV-1 to infect the cells of New World monkeys was examined. Primary cells derived from common marmosets and squirrel monkeys support every phase of HIV-1 replication with the exception of virus entry. Efficient HIV-1 entry typically requires binding of the viral envelope glycoproteins and host cell receptors, CD4 and either CCR5 or CXCR4 chemokine receptors. HIV-1 did not detectably bind or utilize squirrel monkey CD4 for entry, and marmoset CD4 was also very inefficient compared with human CD4. A marmoset CD4 variant, in which residues 48 and 59 were altered to the amino acids Found in human CD4, supported HIV-1 entry efficiently. The CXCR4 molecules of both marmosets and squirrel monkeys supported HIV-1 infection, but the CCR5 proteins of both species were only marginally functional. These results demonstrate that the CD4 and CCR5 proteins of New World monkeys represent the major restriction against HIV-1 replication in these primates. Directed adaptation of the HIV-1 envelope glycoproteins to common marmoset receptors might allow the development of New World monkey models of HIV-1 infection. C1 Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Aids, JFB 824,44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [P50 HL054785, HL 54785]; NIAID NIH HHS [R01 AI041851, AI 28691, AI 41851, P30 AI028691] NR 81 TC 28 Z9 31 U1 1 U2 3 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 AUG 19 PY 2002 VL 196 IS 4 BP 431 EP 445 DI 10.1084/jem.20020468 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 587XK UT WOS:000177669300003 PM 12186836 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 ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract 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 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 049-TOXI BP U369 EP U369 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422201806 ER PT J AU Doherty, SA Lewandrowski, KU Hile, DD Wise, DL Trantolo, DJ AF Doherty, SA Lewandrowski, KU Hile, DD Wise, DL Trantolo, DJ TI Biocompatibility of a bioresorbable bone graft substitute for mandibular reconstruction. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 103-PMSE BP U504 EP U504 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RM UT WOS:000177422302744 ER PT J AU Greco, JB Sakaie, KE Westmoreland, S He, J Aminipour, S Seghal, P Cheng, LL Lee, PL Lackner, A Gonzalez, RG AF Greco, JB Sakaie, KE Westmoreland, S He, J Aminipour, S Seghal, P Cheng, LL Lee, PL Lackner, A Gonzalez, RG TI In vivo and ex vivo NMR in the study of the pathogenesis of AIDS dementia. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. New England Primate Res Ctr, Div Pathol, Southborough, MA 01772 USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 148-BIOL BP U178 EP U178 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200827 ER PT J AU Hile, DD Lewandrowski, KU Doherty, SA Wise, DL Trantolo, DJ AF Hile, DD Lewandrowski, KU Doherty, SA Wise, DL Trantolo, DJ TI Osteoinduction in a resorbable bone graft extender. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 105-PMSE BP U505 EP U505 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RM UT WOS:000177422302746 ER PT J AU McLaughlin, BJ Singh, S Mohay, J Hadlock, T Woerly, S Vacanti, JP Wood, TO AF McLaughlin, BJ Singh, S Mohay, J Hadlock, T Woerly, S Vacanti, JP Wood, TO TI Polymers for ocular monolayer transplantation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Louisville, Dept Ophthalmol & Visual Sci, Abell Adm Ctr, Louisville, KY 40202 USA. Childrens Hosp, Massachusetts Eye & Ear Infirm, Dept Surg, Dept Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 231-PMSE BP U525 EP U525 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RM UT WOS:000177422302870 ER PT J AU Nouri, M Dohlman, CH AF Nouri, M Dohlman, CH TI Clinical experiences with a polymethyl methacrylate keratoprosthesis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 219-PMSE BP U523 EP U523 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RM UT WOS:000177422302858 ER PT J AU Pelish, HE Feng, Y Peterson, JR Westwood, NJ Tsai, AL Kirschner, MW Kirchhausen, T Shair, MD AF Pelish, HE Feng, Y Peterson, JR Westwood, NJ Tsai, AL Kirschner, MW Kirchhausen, T Shair, MD TI Secramine: An inhibitor of export from the Golgi apparatus discovered through biomimetic diversity-oriented synthesis and screening. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Inst Chem & Cell Biol, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Harvard Univ, Inst Chem & Cell Biol, Dept Cell Biol, Ctr Blood Res, Cambridge, MA 02138 USA. 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 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 200-MEDI BP U40 EP U40 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RM UT WOS:000177422300200 ER PT J AU Roberts, KA Lee, KB Yarmush, ML Jayaraman, A AF Roberts, KA Lee, KB Yarmush, ML Jayaraman, A TI Proteomic analysis of secreted protein dynamics in hepatocytes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Burn Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RI Lee, Kyongbum/D-9230-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 012-BIOT BP U199 EP U200 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200876 ER PT J AU Tung, CH Weissleder, R AF Tung, CH Weissleder, R TI Novel near infrared fluorescence probes for in vivo protease activity sensing. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 409-MEDI BP U78 EP U78 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RM UT WOS:000177422300409 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 ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Max Planck Inst Biochem, Martinsried, Germany. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RI Hill, David/B-6617-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 006-TOXI BP U361 EP U362 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422201763 ER PT J AU Zamecnik, PC AF Zamecnik, PC TI Diadenosine polyphosphates: The beginning. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 022-CARB BP U262 EP U262 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422203930 ER PT J AU Kohane, DS Plesnila, N Thomas, SS Le, D Langer, R Moskowitz, MA AF Kohane, DS Plesnila, N Thomas, SS Le, D Langer, R Moskowitz, MA TI Lipid-sugar particles for intracranial drug delivery: safety and biocompatibility SO BRAIN RESEARCH LA English DT Article DE regional cerebral blood flow ID BRAIN AB Controlled release of drugs to specific locales in the brain has engendered considerable interest. Here we evaluate the safety and biocompatibility of 6-mum diameter particles composed of dipalmitoylphosphatidylcholine and chondroitin sulfate A, when delivered into the cerebral parenchyma and ventricles, and in the case of intravascular injection. Some particles were loaded with fluorescein-labeled albumin to facilitate detection. Particles placed in medium with cultured murine primary cortical neurons did not increase cell death at concentrations as high as 4 mg/ml. When particles (100 mug in 2 mul) were placed stereotactically in the striatum and lateral ventricles, there was no histological evidence on hematoxylin-eosin stained sections of tissue injury outside of the needle track in any animal 3, 7, and 14 days after injection (n=6 each), and no inflammation. Ventricular size was not significantly different between animals given intraventricular injections of particles and albumin solution at those time points (n=4 each). Intracarotid injection of particles at concentrations of 0.2 and I mg/ml (n=4 each) did not affect relative cerebral blood flow, and there were no embolic events on histology. In one animal in the group injected with 5 mg/ml (n=3), there was a profound decrease in rCBF, with patchy emboli on histology. These novel biodegradable particles are biocompatible in and around the brain, and may be safe for intracranial sustained drug delivery either in the parenchyma or into the CSF. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Neurosci, Stroke & Neurovasc Regulat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Stroke & Neurovasc Regulat Lab, Boston, MA 02114 USA. RI Moskowitz, Michael/D-9916-2011 FU NIGMS NIH HHS [GM26698, GM00684]; NINDS NIH HHS [NS10828, NS374141] NR 15 TC 24 Z9 24 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 16 PY 2002 VL 946 IS 2 BP 206 EP 213 AR PII S0006-8993(02)02878-0 DI 10.1016/S0006-8993(02)02878-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 587WT UT WOS:000177667500007 PM 12137923 ER PT J AU Farzan, M Babcock, GJ Vasilieva, N Wright, PL Kiprilov, E Mirzabekov, T Choe, H AF Farzan, M Babcock, GJ Vasilieva, N Wright, PL Kiprilov, E Mirzabekov, T Choe, H TI The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1 alpha association and HIV-1 entry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR CXCR4; TETRASACCHARIDE SEQUENCE; SULFATED TYROSINES; N-TERMINUS; CCR5; 7-TRANSMEMBRANE; INFECTION; LIGAND; REGION AB The chemokine receptor CXCR4 plays critical roles in development, immune function, and human immunodeficiency virus type 1 (HIV-1) entry. Here we demonstrate that, like the CC-chemokine receptors CCR5 and CCR2b, CXCR4 is posttranslationally modified by sulfation of its amino-terminal tyrosines. The sulfate group at tyrosine 21 contributes substantially to the ability of CXCR4 to bind its ligand, stromal derived factor la. Tyrosine sulfation plays a less significant role in CXCR4-dependent HIV-1 entry than in CCR5-dependent HIV-1 entry. In some cell lines, CXCR4 is efficiently modified by a chondroitin sulfate chain at serine 18, but neither HIV-1 entry nor stromal derived factor la binding was affected by loss of this glycosaminoglycan. These data demonstrate a functional role for tyrosine sulfate in the CXC-chemokine receptor family and underscore a general difference in HIV-1 utilization of CCR5 and CXCR4. C1 Harvard Univ, Childrens Hosp, Sch Med, Ina Sue Perlmutter Lab,Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Canc Immunol & AIDS, Div AIDS,Dept Pathol, Boston, MA 02115 USA. RP Choe, H (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Ina Sue Perlmutter Lab,Dept Pediat, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI48425, AI43891, R01 AI043891] NR 28 TC 135 Z9 142 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 AUG 16 PY 2002 VL 277 IS 33 BP 29484 EP 29489 DI 10.1074/jbc.M203361200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 585DW UT WOS:000177509300019 PM 12034737 ER PT J AU Plotnick, MI Rubin, H Schechter, NM AF Plotnick, MI Rubin, H Schechter, NM TI The effects of reactive site location on the inhibitory properties of the serpin alpha(1)-antichymotrypsin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-SHEET-A; PLASMA PROTEINASE-INHIBITORS; HUMAN NEUTROPHIL ELASTASE; CENTER LOOP; ALPHA(1)-PROTEINASE INHIBITOR; PLASMINOGEN-ACTIVATOR; HUMAN CHYMASE; COMPLEX; CHYMOTRYPSIN; INSERTION AB The large size of the serpin reactive site loop (RSL) suggests that the role of the RSL in protease inhibition is more complex than that of presenting the reactive site (P1 residue) to the protease. This study examines the effect on inhibition of relocating the reactive site (Leu-358) of the serpin alpha(1)-antichymotrypsin either one residue closer (P2) or further (P1') from the base of the RSL (Glu-342). alpha(1)-Antichymotrypsin variants were produced by mutation within the P4-P2' region; the sequence ITLLSA was changed to ITLSSA to relocate the reactive site to P2 (Leu-357) and to ITITLS to relocate it to P1' (Leu-359). Inhibition of the chymotrypsin-like proteases human chymase and chymotrypsin and the non-target protease human neutrophil elastase (HNE) were analyzed. The P2 variant inhibited chymase and chymotrypsin but not HNE. Relative to P1, interaction at P2 was characterized by greater complex stability, lower inhibition rate constants, and increased stoichiometry of inhibition values. In contrast, the P1' variant inhibited HNE (stoichiometry of inhibition = 4) but not chymase or chymotrypsin. However, inhibition of HNE was by interaction with Ile-357, the P2 residue. The P1' site was recognized by all proteases as a cleavage site. Covalent-complexes resistant to SDS-PAGE were observed in all inhibitory reactions, consistent with the trapping of the protease as a serpin-acyl protease complex. The complete loss in inhibitory activity associated with lengthening the Glu-342-reactive site distance by a single residue and the enhanced stability of complexes associated with shortening this distance by a single residue are compatible with the distorted-protease model of inhibition requiring full insertion of the RSL into the body of the serpin and translocation of the linked protease to the pole opposite from that of encounter. C1 Univ Penn, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. Philadelphia Vet Affais Med Ctr, Philadelphia, PA 19104 USA. RP Plotnick, MI (reprint author), Hosp Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Maloney Bldg 8th Fl,36th & Spruce Sts, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [HL03495, HL50523]; NIAMS NIH HHS [AR39674] NR 51 TC 10 Z9 10 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 AUG 16 PY 2002 VL 277 IS 33 BP 29927 EP 29935 DI 10.1074/jbc.M202374200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 585DW UT WOS:000177509300073 PM 12055188 ER PT J AU Kaneto, H Xu, G Fujii, N Kim, S Bonner-Weir, S Weir, GC AF Kaneto, H Xu, G Fujii, N Kim, S Bonner-Weir, S Weir, GC TI Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC BETA-CELLS; HOMEODOMAIN PROTEIN IDX-1; NITRIC-OXIDE; TRANSCRIPTIONAL ACTIVATION; DIABETES-MELLITUS; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; SUPEROXIDE PRODUCTION; HEXOSAMINE PATHWAY; GLYCATION REACTION; PROMOTER ACTIVITY AB Oxidative stress, which is found in pancreatic beta-cells in the diabetic state, suppresses insulin gene transcription and secretion, but the signaling pathways involved in the beta-cell dysfunction induced by oxidative stress remain unknown. In this study, subjecting rat islets to oxidative stress activates JNK, p38 MAPK, and protein kinase C, preceding the decrease of insulin gene expression. Adenovirus-mediated overexpression of dominant-negative type (DN) JNK, but not the p38 MAPK inhibitor SB203580 nor the protein kinase C inhibitor GF109203X, protected insulin gene expression and secretion from oxidative stress. Moreover, wild type JNK overexpression suppressed both insulin gene expression and secretion. These results were correlated with changes in the binding of the important transcription factor PDX-1 to the insulin promoter; adenoviral overexpression of DN-JNK preserved PDX-1 DNA binding activity in the face of oxidative stress, whereas wild type JNK overexpression decreased PDX-1 DNA binding activity. Furthermore, to examine whether suppression of the JNK pathway can protect beta-cells from the toxic effects of hyperglycemia, rat islets were infected with DN-JNK expressing adenovirus or control adenovirus and transplanted under renal capsules of streptozotocin-induced diabetic nude mice. In mice receiving DN-JNK overexpressing islets, insulin gene expression in islet grafts was preserved, and hyperglycemia was ameliorated compared with control mice. In conclusion, activation of JNK is involved in the reduction of insulin gene expression by oxidative stress, and suppression of the JNK pathway protects beta-cells from oxidative stress. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Osaka City Univ, Sch Med, Dept Pharmacol, Osaka 545, Japan. Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIDDK NIH HHS [DK-35449, DK-36836] NR 77 TC 193 Z9 205 U1 4 U2 11 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 AUG 16 PY 2002 VL 277 IS 33 BP 30010 EP 30018 DI 10.1074/jbc.M202066200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 585DW UT WOS:000177509300082 PM 12011047 ER PT J AU Takemoto, CM Yoon, YH Fisher, DE AF Takemoto, CM Yoon, YH Fisher, DE TI The identification and functional characterization of a novel mast cell isoform of the microphthalmia-associated transcription factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HELIX-LOOP-HELIX; MI LOCUS; IMPAIRED EXPRESSION; GENE-EXPRESSION; MI/MI GENOTYPE; TIETZ-SYNDROME; MUTANT MICE; INVOLVEMENT; RECEPTOR; ZIPPER AB The microphthalmia-associated transcription factor (Mitf) is critical for mast cell development based on the severe mast cell deficiency seen in Mitf mutant mice. Mitf also is important for the development of melanocytes, osteoclasts, and retinal pigment epithelium. The lineage-restricted phenotypes of Mitf mutations correlate with tissue-restricted expression of Mitf, a feature due in part to the presence of several distinct Mitf isoforms. We report the identification and characterization of a novel mast cell isoform, Mitf-mc. This isoform arises from alternative splicing of a novel 5'-exon onto the common body of the gene and is predicted to encode a unique 43-amino acid sequence at its amino terminus. It is specifically expressed in mast cells. The mast cell isoform functions differently from the melanocyte isoform in its ability to activate cell type-specific Mitf gene targets. Mitf-me functions only on a mast cell target promoter and fails to activate a melanocyte target promoter despite binding to its E-box element. Moreover, Mitf-me heterodimerizes with a closely related transcription factor, Tfe3, and dominantly inhibits the ability of Tfe3 to transactivate a melanocyte-specific promoter. These studies identify a new isoform of Mitf with tissue-specific features that may underlie key aspects of the mast cell phenotype of Mitf mutations. C1 Johns Hopkins Univ, Div Pediat Hematol, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Takemoto, CM (reprint author), Johns Hopkins Univ, Div Pediat Hematol, 720 Rutland Ave, Baltimore, MD 21205 USA. FU NHLBI NIH HHS [K08HL03700-05]; NICHD NIH HHS [P30HD27799] NR 36 TC 60 Z9 60 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 AUG 16 PY 2002 VL 277 IS 33 BP 30244 EP 30252 DI 10.1074/jbc.M201441200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 585DW UT WOS:000177509300110 PM 12039954 ER PT J AU Woolf, CJ Bloechlinger, S AF Woolf, CJ Bloechlinger, S TI Neuroscience: It takes more than two to Nogo SO SCIENCE LA English DT Editorial Material ID NEURITE GROWTH-INHIBITORS; SPINAL-CORD INJURY; AXON REGENERATION; RECOVERY; PROTEIN; CNS C1 Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, Boston, MA 02129 USA. NR 17 TC 47 Z9 71 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 16 PY 2002 VL 297 IS 5584 BP 1132 EP 1134 DI 10.1126/science.1076247 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 584BP UT WOS:000177447600033 PM 12183616 ER PT J AU Lin, AE AF Lin, AE TI O patient, where art thou? SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. RP Lin, AE (reprint author), Brigham & Womens Hosp, Teratol Program, Old PBBH-B501,75 Francis St, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 15 PY 2002 VL 111 IS 3 BP 334 EP 334 DI 10.1002/ajmg.10553 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 579PE UT WOS:000177186400017 PM 12210334 ER PT J AU Park, YB Choi, HK Kim, MY Lee, WK Song, J Kim, DK Lee, SK AF Park, YB Choi, HK Kim, MY Lee, WK Song, J Kim, DK Lee, SK TI Effects of antirheumatic therapy on serum lipid levels in patients with rheumatoid arthritis: A prospective study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ACUTE-PHASE RESPONSE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; C-REACTIVE PROTEIN; HDL-CHOLESTEROL; CARDIOVASCULAR-DISEASE; WOMEN; ATHEROSCLEROSIS; INFLAMMATION AB BACKGROUND: Patients with newly diagnosed rheumatoid arthritis have adverse serum lipid profiles. We sought to determine the effects of treating rheumatoid arthritis with antirheumatic drugs on these abnormal lipid levels. SUBJECTS AND METHODS: We studied 42 patients with newly diagnosed rheumatoid arthritis who had not been treated with corticosteroids or disease-modifying antirheumatic drugs. We measured serum lipid profiles at baseline and 1 year later, and determined whether there were differences in the changes in lipid levels between patients who met the American College of Rheumatology criteria for a 20% improvement in rheumatoid arthritis and those who did not. RESULTS: Of the 42 patients, 27 (64%) met the criteria for a 20% improvement in rheumatoid arthritis during the 12 month study. In these patients, mean high-density lipoprotein (HDL) cholesterol levels increased by 21% (P<0.001), apoli-poprotein A-1 levels increased by 23% (P<0.001), and the ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol level decreased by 13% (P=0. 10). There were significant between-group differences (responders-nonresponders) in the mean 12-month changes in HDL cholesterol levels (8.0 mg/dL; 95% confidence interval [CI]: 3 to 13 mg/dL; P=0.002), apoli-poprotein A-I levels (21 mg/dL; 95% Cl: 8 to 33 mg/dL; P=0.003), and the LDL cholesterol to HDL cholesterol ratio (-0.6; 95% CI: -0.1 to -1.0; P=0.03), but not in LDL cholesterol, apolipoprotein B-100, or lipoprotein(a) levels. CONCLUSION: Active rheumatoid arthritis is associated with an adverse lipid profile that improves substantially following effective treatment of rheumatoid arthritis. This improvement may reduce the risk of cardiovascular disease. (C) 2002 by Excerpta Medica, Inc. C1 Yonsei Univ, Coll Med,BK Project Med Sci 21, Dept Internal Med,Inst Immunol & Immunol Dis, Div Rheumatol,Seodaemun Ku, Seoul 120752, South Korea. Yonsei Univ, Grad Sch, Seoul 120749, South Korea. Yonsei Univ, Coll Med, Dept Biostat, Seoul 120752, South Korea. Massachusetts Gen Hosp, Dept Med, Arthritis Unit, Boston, MA 02114 USA. RP Lee, SK (reprint author), Yonsei Univ, Coll Med,BK Project Med Sci 21, Dept Internal Med,Inst Immunol & Immunol Dis, Div Rheumatol,Seodaemun Ku, Shinchon Dong 134,CPO Box 8044, Seoul 120752, South Korea. NR 36 TC 124 Z9 129 U1 0 U2 0 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 AUG 15 PY 2002 VL 113 IS 3 BP 188 EP 193 AR PII S0002-9343(02)01186-5 DI 10.1016/S0002-9343(02)01186-5 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 588TW UT WOS:000177717900002 PM 12208376 ER PT J AU Isselbacher, EM AF Isselbacher, EM TI Intramural hematoma of the aorta: Should we let down our guard.? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID DISSECTION; HEMORRHAGE C1 Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. NR 11 TC 6 Z9 6 U1 0 U2 1 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 AUG 15 PY 2002 VL 113 IS 3 BP 244 EP 246 AR PII S0002-9343(02)01232-9 DI 10.1016/S0002-9343(02)01232-9 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 588TW UT WOS:000177717900013 PM 12208387 ER PT J AU Voldman, J Gray, ML Toner, M Schmidt, MA AF Voldman, J Gray, ML Toner, M Schmidt, MA TI A microfabrication-based dynamic array cytometer SO ANALYTICAL CHEMISTRY LA English DT Article ID GENE-EXPRESSION; LIVING CELLS; MANIPULATION; FIELD; DIELECTROPHORESIS; LEVITATION; PARTICLES; TRAPS; BIOPARTICLES; ACTIVATION AB We have developed a microfabricated device for use in parallel luminescent single-cell assays that can sort populations upon the basis of dynamic functional responses to stimuli. Ibis device is composed of a regular array of noncontact single-cell traps. These traps use dielectrophoresis to stably confine cells and hold them against disrupting fluid flows. Using quantitative modeling, we have designed traps with a novel asymmetric extruded-quadrupole geometry. This new trap can be physically arrayed and electrically addressed, enabling our cytometer. Situating an array of these traps in a microchannel, we have introduced cells into the array and demonstrated observation of fluorescent dynamic responses followed by sorting. Such a device has potential for use in investigating functional processes, as revealed by temporal behavior, in large numbers of single cells. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Voldman, J (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NIGMS NIH HHS [1U54GM62114-01] NR 47 TC 239 Z9 245 U1 1 U2 50 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD AUG 15 PY 2002 VL 74 IS 16 BP 3984 EP 3990 DI 10.1021/ac0256235 PG 7 WC Chemistry, Analytical SC Chemistry GA 585BF UT WOS:000177502700007 PM 12199564 ER PT J AU Kemp, DM Habener, JF AF Kemp, DM Habener, JF TI Synergistic effect of dimethyl sulfoxide on glucagon-like peptide 1 (GLP-1)-stimulated insulin secretion and gene transcription in INS-1 cells: characterization and implications SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE dimethyl sulfoxide; insulin; INS-1; pancreatic beta-cell; GLP-1; glucagon-like peptide 1 ID CAMP-RESPONSIVE ELEMENT; INDUCED DIFFERENTIATION; SODIUM-BUTYRATE; STEM-CELLS; I GENE; EXPRESSION; PROTEIN; DIMETHYLSULFOXIDE; LINE; HORMONE AB Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is secreted from the enteroendocrine L-cells of the gut in response to nutrient ingestion. GLP-1 enhances both insulin secretion and insulin gene expression in a glucose-dependent manner via activation of its putative G-protein-coupled receptor on pancreatic beta-cells. In the presence of DMSO (0.5-2.5%), these functional responses were enhanced significantly (2- to 2.5-fold) in a concentration-dependent manner in the (beta-cell line INS-1, although basal levels were not affected. Rat insulin 1 (rINS1) promoter activity appeared to be augmented in a cAMP-response element (CRE)-dependent manner as the effect of DMSO was abolished following a mutation in the CRE of the rINS1 promoter. Also, expression of a generic cAMP-driven reporter gene was enhanced by 1.5% DMSO in response to GLP-1(3.5-fold), forskolin (2-fold), and 3-isobutyl-1-methylxanthine (2-fold). Analysis of intracellular signaling components revealed that DMSO did not elevate cAMP levels, protein kinase A activity, or phosphorylated levels of CRE-binding protein (CREB), CRE-modulator (CREM), and activating transcription factor-1 (ATF-1). These data suggest that GLP-1 induces insulin gene transcription in a CREB, CREM, and ATF-1-independent manner in beta-cells. The mechanism by which DMSO imparts this amplifying action is unclear but may involve redistribution of intracellular compartments or a direct molecular interaction with a downstream target of the GLP-1 receptor signaling pathway in the [beta-cell. These effects of DMSO on incretin action may provide novel applications with respect to further characterizing GLP-1 receptor signaling, identifying incretin-like compounds in screening assays, and as a therapeutic treatment in type 2 diabetes. (C) 2002 Elsevier Science Inc. All rights reserved, C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK30834] NR 28 TC 10 Z9 11 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 15 PY 2002 VL 64 IS 4 BP 689 EP 697 AR PII S0006-2952(02)01212-1 DI 10.1016/S0006-2952(02)01212-1 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 589UD UT WOS:000177778000015 PM 12167488 ER PT J AU Sethi, S Ziouzenkova, O Ni, HY Wagner, DD Plutzky, J Mayadas, TN AF Sethi, S Ziouzenkova, O Ni, HY Wagner, DD Plutzky, J Mayadas, TN TI Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothehal interactions through activation of PPAR alpha SO BLOOD LA English DT Article ID CORONARY HEART-DISEASE; RECEPTOR-ALPHA; HYPERLIPIDEMIC DIET; LIPID-PEROXIDATION; NUCLEAR RECEPTORS; GAMMA ACTIVATORS; IGA NEPHROPATHY; SOLUBLE MARKERS; KAPPA-B; CELLS AB Omega-3 fatty acids, which are abundant In fish oil, improve the prognosis of several chronic inflammatory diseases although the mechanism for such effects remains unclear. These fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. We show that oxidized, but not native unoxidized, EPA significantly inhibited human neutrophil and monocyte adhesion to endothelial cells in vitro by inhibiting endothelial adhesion receptor expression. In transcriptional coactivation assays, oxidized EPA potently activated the peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor family. In vivo, oxidized, but not native, EPA markedly reduced leukocyte rolling and adhesion to venular endothelium of lipopolysaccharide (LPS)-treated mice. This occurred via a PPARalpha-dependent mechanism because oxidized EPA had no such effect in LPS-treated PPARalpha-deficient mice. Therefore, the beneficial effects of omega-3 fatty acids may be explained by a PPARalpha-mediated anti-inflammatory effect of oxidized EPA. (C) 2002 by The American Society of Hematology. C1 Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02130 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02130 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Mayadas, TN (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, 221 Longwood Ave,Room 404, Boston, MA 02130 USA. RI Ziouzenkova, Ouliana/B-3690-2012 FU NHLBI NIH HHS [HL36028, HL53756, R01 HL053756] NR 48 TC 88 Z9 93 U1 0 U2 8 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 AUG 15 PY 2002 VL 100 IS 4 BP 1340 EP 1346 DI 10.1182/blood-2002-01-0316 PG 7 WC Hematology SC Hematology GA 582RG UT WOS:000177364500031 PM 12149216 ER PT J AU Michaelson, JS Silverstein, M Wyatt, J Weber, G Moore, R Halpern, E Kopans, DB Hughes, K AF Michaelson, JS Silverstein, M Wyatt, J Weber, G Moore, R Halpern, E Kopans, DB Hughes, K TI Predicting the survival of patients with breast carcinoma using tumor size SO CANCER LA English DT Article DE breast carcinoma; tumor size; metastasis; survival; mammography ID TERM FOLLOW-UP; NATURAL-HISTORY; CLINICAL IMPLICATIONS; PROGNOSTIC MARKERS; CANCER; ANGIOGENESIS; MAMMOGRAPHY; MECHANISMS; DIAGNOSIS; GROWTH AB BACKGROUND. Tumor size has long been recognized as the strongest predictor of the outcome of patients with invasive breast carcinoma, although it has not been settled whether the correlation between tumor size and the chance of death is independent of the method of detection, nor is it clear how tumor size at the time of treatment may be translated into a specific expectation of survival. In this report, the authors provide such a method. METHODS. A Kaplan-Meier survival analysis was carried out for a population of 1352 women with invasive breast carcinoma who were treated at the Van Nuys Breast Center between 1966 and 1990, and the data were analyzed together with survival data published by others. RESULTS. The authors found that the survival of patients with invasive breast carcinoma was a direct function of tumor size, independent of the method of detection. The results showed that the correlation between tumor size and survival was well fit by a simple equation, with which survival predictions could be made from information on tumor size. For example, a comparison of three large populations studied over the last 5 decades revealed a marked improvement (approximate to35% absolute) in the survival of patients with invasive breast carcinoma diagnosed on clinical grounds that could be ascribed to a reduction in tumor size. However, the capacity of screening mammography to find smaller tumors remains the best way reduce breast carcinoma deaths, with the potential for adding an additional approximate to20% absolute reduction in breast carcinoma deaths. The mathematic correlation between tumor size and survival is consistent with a biologic mechanism in which lethal distant metastasis occurs by discrete events of spread such that, for every invasive breast carcinoma cell in the primary tumor at the time of surgery, there is approximately a 1-in-1-billion chance that a lethal distant metastasis has formed. CONCLUSIONS. The correlation between tumor size and lethality is well captured by a simple equation that is consistent with breast carcinoma death as the result of discrete events of cellular spread occurring with small but definable probabilities. (C) 2002 American Cancer Society. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. Univ So Calif, Harold E & Henrietta C Lee Breast Ctr, USC Norris Canc Ctr, Los Angeles, CA USA. MIT, Dept Elect Engn, Cambridge, MA 02139 USA. Harvard Univ, Dept Radiol, Sch Med, Boston, MA 02115 USA. RP Michaelson, JS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Cox Bldg,Room 626,100 Blossom St, Boston, MA 02114 USA. OI Weber, Griffin/0000-0002-2597-881X; Hughes, Kevin/0000-0003-4084-6484 NR 45 TC 107 Z9 111 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2002 VL 95 IS 4 BP 713 EP 723 DI 10.1002/cncr.10742 PG 11 WC Oncology SC Oncology GA 580MP UT WOS:000177238600006 PM 12209713 ER PT J AU Crawford, J Cella, D Cleeland, CS Cremieux, PY Demetri, GD Sarokhan, BJ Slavin, MB Glaspy, JA AF Crawford, J Cella, D Cleeland, CS Cremieux, PY Demetri, GD Sarokhan, BJ Slavin, MB Glaspy, JA TI Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy SO CANCER LA English DT Article DE anemia; quality of life; erythropoietin; epoetin alfa; hemoglobin; neoplasm ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CHRONIC DIALYSIS PATIENTS; CELL LUNG-CANCER; OF-LIFE; HEMODIALYSIS-PATIENTS; SAMPLE SELECTION; FUNCTIONAL ASSESSMENT; COMMUNITY ONCOLOGY; DOUBLE-BLIND; DISEASE AB BACKGROUND. Hemoglobin increases have been associated with quality of life (QOL) improvements in anemic cancer patients treated with epoetin alfa, but intervention generally has been reserved for symptomatic anemia or hemoglobin < 10 g/dL. Relationships among hemoglobin, functional status, and patient reported QOL have not been well characterized. METHODS. Data from two open-label, community-based trials of epoetin alfa therapy that enrolled 4382 anemic cancer patients undergoing chemotherapy were used to evaluate the relationship between hemoglobin changes and QOL changes. The authors measured QOL using the Linear Analog Scale Assessment (LASA) and the more detailed, disease-specific Functional Assessment of Cancer Therapy-Anemia (FACT-An) instrument. Analyses were performed to determine the incremental change in QOL associated with hemoglobin increases (I g/dL increments). RESULTS. Cross-sectional analyses showed a nonlinear relationship and significant positive correlation between high hemoglobin levels and high LASA and FACT-An scores (r = 0.25 and 0.29, respectively, P < 0.01). Patients with hemoglobin increases of : 2 g/dL reported statistically significant improvements in five FACT-An items selected a priori specifically to reflect functional capacity. An incremental analysis used regression methods to identify the longitudinal relationship between incremental changes in hemoglobin and QOL scores. This relationship was found to be nonlinear, with the maximum QOL gain occurring at a hemoglobin level of 12 g/dL (range, 11-13 g/dL). Patients with low baseline QOL scores and longer time periods between baseline and final QOL assessments experienced significantly (P < 0.05) greater increases in overall QCL. Progressive disease at baseline, change in disease status from baseline to end of study, and increase in self-reported pain or nausea all had significant (P < 0.05) negative effects on QOL scores. CONCLUSIONS. A direct relationship exists between hemoglobin increases during epoetin alfa therapy and corresponding QOL improvements in cancer patients receiving chemotherapy across the clinically relevant hemoglobin range of 8-14 g/dL. These data suggest that the maximal incremental gain in QOL occurs when hemoglobin is in the range of 11-13 g/dL. (C) 2002 American Cancer Society. C1 Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. Duke Univ, Med Ctr, Ctr Comprehens Canc, Durham, NC 27710 USA. Evanston NW Healthcare, Ctr Outcomes Res & Educ, Evanston, IL USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Anal Grp Econ, Cambridge, MA USA. Univ Quebec, Montreal, PQ H3C 3P8, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Ortho Biotech Prod, LP, Raritan, NJ USA. RP Glaspy, JA (reprint author), Suite 202,200 Med Plaza, Los Angeles, CA 90095 USA. NR 43 TC 252 Z9 261 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2002 VL 95 IS 4 BP 888 EP 895 DI 10.1002/cncr.10763 PG 8 WC Oncology SC Oncology GA 580MP UT WOS:000177238600027 PM 12209734 ER PT J AU Seth, P Porter, D Lahti-Domenici, J Geng, Y Richardson, A Polyak, K AF Seth, P Porter, D Lahti-Domenici, J Geng, Y Richardson, A Polyak, K TI Cellular and molecular targets of estrogen in normal human breast tissue SO CANCER RESEARCH LA English DT Article ID RECEPTOR SUBUNIT; SERIAL ANALYSIS; OVARIAN-CANCER; EXPRESSION; LIPOCALIN; MOUSE; MECHANISM; PROTEINS; LESIONS; SYSTEM AB To gain insight into the in vivo role of estrogen, we isolated estrogen receptor-positive cells from normal human breast tissue using a recombinant adenovirus that expresses green fluorescence protein in response to estrogen. We compared the global gene expression profile of these estrogen receptor-positive cells with that of various normal and cancerous mammary epithelial cells and identified several genes not implicated previously in estrogen signaling. One of these genes, lipocalin 2, is a putative in vivo estrogen target gene and paracrine factor that mediates the growth regulatory effects of estrogen in normal breast epithelium. These results demonstrate that normal and cancerous estrogen receptor-positive cells are distinct at the molecular level and suggest that lipocalin 2 is a new therapeutic target for breast cancer prevention and treatment. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. NR 24 TC 69 Z9 69 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2002 VL 62 IS 16 BP 4540 EP 4544 PG 5 WC Oncology SC Oncology GA 584YP UT WOS:000177496600002 PM 12183401 ER PT J AU Simko, JP Caliendo, AM Hogle, K Versalovic, J AF Simko, JP Caliendo, AM Hogle, K Versalovic, J TI Differences in laboratory findings for cerebrospinal fluid specimens obtained from patients with meningitis or encephalitis due to herpes simplex virus (HSV) documented by detection of HSV DNA SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; MOLLARETS MENINGITIS; ASEPTIC-MENINGITIS; GENITAL HERPES; REACTION ASSAY; BELL PALSY; DIAGNOSIS; TYPE-2; PCR AB Laboratory findings for cerebrospinal fluid (CSF) specimens were correlated with clinical presentations and histories in 55 cases of encephalitis or meningitis due to herpes simplex virus (HSV), as determined by polymerase chain reaction (PCR)-based detection of HSV DNA. Sixteen patients (29%) had HSV encephalitis (HSVE), 3 had mild or "atypical" meningoencephalitis, 34 (64%) had HSV meningitis (HSVM), and 1 had disseminated neonatal HSV infection. CSF findings included elevated leukocyte counts and/or elevated CSF protein levels in all HIV DNA-positive specimens. CSF leukocyte and protein abnormalities were more pronounced in cases of HSVM than they are in cases of HSVE. Patients with HSVE who had only mild CSF abnormalities also had minimal numbers of erythrocytes in the CSF. Patients with HSVM were younger than were patients with HSVE and were predominantly female. Eleven patients with HSVM reported having prior episodes, and 5 reported a history of recurrent headaches. These findings suggest that milder forms of HSV infection of the central nervous system may be identified by PCR for HSV. Prescreening of CSF specimens for the presence of leukocytes or elevated protein level may improve test utilization. C1 Emory Univ Hosp, Dept Pathol & Lab Med, Clin Lab, Atlanta, GA 30322 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Emory Univ, Sch Med, Atlanta, GA USA. RP Caliendo, AM (reprint author), Emory Univ Hosp, Dept Pathol & Lab Med, Clin Lab, H180,1364 Clifton Rd, Atlanta, GA 30322 USA. NR 46 TC 24 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 15 PY 2002 VL 35 IS 4 BP 414 EP 419 DI 10.1086/341979 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 578HQ UT WOS:000177111700011 PM 12145725 ER PT J AU Finegold, SM Flynn, MJ Rose, FV Jousimies-Somer, H Jakielaszek, C McTeague, M Wexler, HM Berkowitz, E Wynne, B AF Finegold, SM Flynn, MJ Rose, FV Jousimies-Somer, H Jakielaszek, C McTeague, M Wexler, HM Berkowitz, E Wynne, B TI Bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANAEROBIC-BACTERIA; MICROBIOLOGY; SPECIMENS AB An open-label, multicenter study was performed to assess bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults. Seventy aerobic (52.2%) and 64 anaerobic (47.8%) pathogens were recovered from clinically evaluable patients at baseline (before therapy). The most commonly isolated anaerobes were Prevotella species (31.1%), anaerobic streptococci (21.9%), and Fusobacterium species (15.6%). The aerobes most frequently recovered included Streptococcus species (21.4%), Haemophilus influenzae (15.7%), Pseudomonas aeruginosa (15.7%), and Staphylococcus aureus and Moraxella catarrhalis (10.0% each). Recurrences of signs or symptoms of bacterial maxillary sinusitis associated with anaerobes were twice as frequent as were those associated with aerobes when counts of anaerobes were greater than or equal to10(3) cfu/mL. A pathogenic role for Granulicatella species in cases of chronic sinusitis was documented for the first time. C1 W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect 111 F, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. GlaxoSmithKline Pharmaceut, Collegeville, PA USA. RP Finegold, SM (reprint author), W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect 111 F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 15 TC 62 Z9 69 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 15 PY 2002 VL 35 IS 4 BP 428 EP 433 DI 10.1086/341899 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 578HQ UT WOS:000177111700013 PM 12145727 ER PT J AU Shim, EY Walker, AK Shi, Y Blackwell, TK AF Shim, EY Walker, AK Shi, Y Blackwell, TK TI CDK-9/cyclin T (P-TEFb) is required in two postinitiation pathways for transcription in the C-elegans embryo SO GENES & DEVELOPMENT LA English DT Article DE transcription; C. elegans; P-TEFb; CDK9; DSIF; SPT5 ID RNA-POLYMERASE-II; CYCLIN-DEPENDENT KINASE; CARBOXYL-TERMINAL DOMAIN; TBP-LIKE FACTOR; CAENORHABDITIS-ELEGANS; IN-VIVO; ELONGATION-FACTOR; HIV-1 TAT; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER AB The metazoan transcription elongation factor P-TEFb (CDK-9/cyclin T) is essential for HIV transcription, and is recruited by some cellular activators. P-TEFb promotes elongation in vitro by overcoming pausing that requires the SPT-4/SPT-5 complex, but considerable evidence indicates that SPT-4/SPT-5 facilitates elongation in vivo. Here we used RNA interference to investigate P-TEFb functions in vivo, in the Caenorhabditis elegans embryo. We found that P-TEFb is broadly essential for expression of early embryonic genes. P-TEFb is required for phosphorylation of Ser 2 of the RNA Polymerase II C-terminal domain (CTD) repeat, but not for most CTD Ser 5 phosphorylation, supporting the model that P-TEFb phosphorylates CTD Ser 2 during elongation. Remarkably, although heat shock genes are cdk-9-dependent, they can be activated when spt-4 and spt-5 expression is inhibited along with cdk-9. This observation suggests that SPT-4/SPT-5 has an inhibitory function in vivo, and that mutually opposing influences of P-TEFb and SPT-4/SPT-5 may combine to facilitate elongation, or insure fidelity of mRNA production. Other genes are not expressed when cdk-9, spt-4, and spt-5 are inhibited simultaneously, suggesting that these genes require P-TEFb in an additional mechanism, and that they and heat shock genes are regulated through different P-TEFb-dependent elongation pathways. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM62891, GM58012, R01 GM058012, R01 GM062891] NR 83 TC 143 Z9 162 U1 1 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 AUG 15 PY 2002 VL 16 IS 16 BP 2135 EP 2146 DI 10.1101/gad.999002 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 585GM UT WOS:000177517100009 PM 12183367 ER PT J AU Luthi-Carter, R Hanson, SA Strand, AD Bergstrom, DA Chun, WJ Peters, NL Woods, AM Chan, EY Kooperberg, C Krainc, D Young, AB Tapscott, SJ Olson, JM AF Luthi-Carter, R Hanson, SA Strand, AD Bergstrom, DA Chun, WJ Peters, NL Woods, AM Chan, EY Kooperberg, C Krainc, D Young, AB Tapscott, SJ Olson, JM TI Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain SO HUMAN MOLECULAR GENETICS LA English DT Article ID CREB-BINDING PROTEIN; EXPANDED CAG REPEAT; HUNTINGTONS-DISEASE; MOUSE MODEL; MUTANT HUNTINGTIN; MEDIATED TRANSCRIPTION; WIDESPREAD EXPRESSION; TRANSGENIC MICE; STRIATAL CELLS; HD MUTATION AB Previous analyses of gene expression in a mouse model of Huntington's disease (R6/2) indicated that an N-terminal fragment of mutant huntingtin causes downregulation of striatal signaling genes and particularly those normally induced by cAMP and retinoic acid. The present study expands the regional and temporal scope of this previous work by assessing whether similar changes occur in other brain regions affected in Huntington's disease and other polyglutamine diseases and by discerning whether gene expression changes precede the appearance of disease signs. Oligonucleotide microarrays were employed to survey the expression of similar to11 000 mRNAs in the cerebral cortex, cerebellum and striatum of symptomatic R6/2 mice. The number and nature of gene expression changes were similar among these three regions, influenced as expected by regional differences in baseline gene expression. Time-course studies revealed that mRNA changes could only reliably be detected after 4 weeks of age, coincident with development of early pathologic and behavioral changes in these animals. In addition, we discovered that skeletal muscle is also a target of polyglutamine-related perturbations in gene expression, showing changes in mRNAs that are dysregulated in brain and also muscle-specific mRNAs. The complete dataset is available at www.neumetrix.info. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC V5H 4H4, Canada. RP Olson, JM (reprint author), Fred Hutchinson Canc Res Ctr, D4-100,1100 Fairview Ave N, Seattle, WA 98109 USA. RI Chan, Edmond/A-1940-2013 OI Chan, Edmond/0000-0001-9777-0252 FU NIA NIH HHS [AG13617]; NINDS NIH HHS [NS023174, NS10800, NS36086, NS42157] NR 62 TC 247 Z9 248 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 15 PY 2002 VL 11 IS 17 BP 1911 EP 1926 DI 10.1093/hmg/11.17.1911 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 582MX UT WOS:000177356600002 PM 12165554 ER PT J AU Luthi-Carter, R Strand, AD Hanson, SA Kooperberg, C Schilling, G La Spada, AR Merry, DE Young, AB Ross, CA Borchelt, DR Olson, JM AF Luthi-Carter, R Strand, AD Hanson, SA Kooperberg, C Schilling, G La Spada, AR Merry, DE Young, AB Ross, CA Borchelt, DR Olson, JM TI Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects SO HUMAN MOLECULAR GENETICS LA English DT Article ID CREB-BINDING PROTEIN; EXPANDED POLYGLUTAMINE; TRANSGENIC MICE; NEURODEGENERATION; ATROPHIN-1; HD AB Recent evidence indicates that transcriptional abnormalities may play an important role in the pathophysiology of polyglutamine diseases. In the present study, we have explored the extent to which polyglutamine-related changes in gene expression may be independent of protein context by comparing mouse models of dentatorubral-pallidoluysian atrophy (DRPLA) and Huntington's disease (HD). Microarray gene expression profiling was conducted in mice of the same background strain in which the same promoter was employed to direct the expression of full-length atrophin-1 or partial huntingtin transproteins (At-65Q or N171-82Q mice). A large number of overlapping gene expression changes were observed in the cerebella of At-65Q and N171-82Q mice. Six of the gene expression changes common to both huntingtin and atrophin-1 transgenic mice were also observed in the cerebella of mouse models expressing full-length mutant ataxin-7 or the androgen receptor. These results demonstrate that some of the gene expression effects of expanded polyglutamine proteins occur independently of protein context. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neuropathol, Baltimore, MD 21205 USA. Univ Washington, Div Med Genet Med, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Olson, JM (reprint author), Fred Hutchinson Canc Res Ctr, D4-100,1100 Fairview Ave N, Seattle, WA 98109 USA. RI Ross, Christopher/H-8395-2013 FU NIA NIH HHS [AG13617]; NINDS NIH HHS [NS10800, NS16375, NS32214, NS34172, NS38144, NS42157] NR 23 TC 154 Z9 156 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 15 PY 2002 VL 11 IS 17 BP 1927 EP 1937 DI 10.1093/hmg/11.17.1927 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 582MX UT WOS:000177356600003 PM 12165555 ER PT J AU Chan, EYW Luthi-Carter, R Strand, A Solano, SM Hanson, SA DeJohn, MM Kooperberg, C Chase, KO DiFiglia, M Young, AB Leavitt, BR Cha, JHJ Aronin, N Hayden, MR Olson, JM AF Chan, EYW Luthi-Carter, R Strand, A Solano, SM Hanson, SA DeJohn, MM Kooperberg, C Chase, KO DiFiglia, M Young, AB Leavitt, BR Cha, JHJ Aronin, N Hayden, MR Olson, JM TI Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEURONAL INTRANUCLEAR INCLUSIONS; MUTANT HUNTINGTIN; CELLULAR TOXICITY; TRANSGENIC MICE; WILD-TYPE; EXPANDED POLYGLUTAMINE; MEDIATED TRANSCRIPTION; TERMINAL FRAGMENTS; STRIATAL NEURONS; CASPASE CLEAVAGE AB Both transcriptional dysregulation and proteolysis of mutant huntingtin (htt) are postulated to be important components of Huntington's disease (HD) pathogenesis. In previous studies, we demonstrated that transgenic mice that express short mutant htt fragments containing 171 or fewer N-terminal residues (R6/2 and N171-82Q mice) recapitulate many of the mRNA changes observed in human HD brain. To examine whether htt protein length influences the ability of its expanded polyglutamine domain to alter gene expression, we conducted mRNA profiling analyses of mice that express an extended N-terminal fragment (HD46, HD100; 964 amino acids) or full-length (YAC72; 3144 amino acids) mutant htt transprotein. Oligonucleotide microarray analyses of HD46 and YAC72 mice identified fewer differentially expressed mRNAs than were seen in transgenic mice expressing short N-terminal mutant htt fragments. Histologic analyses also detected limited changes in these mice (small decreases in adenosine A2a receptor mRNA and dopamine D2 receptor binding in HD100 animals; small increases in dopamine D1 receptor binding in HD46 and HD100 mice). Neither HD46 nor YAC72 mice exhibited altered mRNA levels similar to those observed previously in R6/2 mice, N171-82Q mice or human HD patients. These findings suggest that htt protein length influences the ability of an expanded polyglutamine domain to alter gene expression. Furthermore, our findings suggest that short N-terminal fragments of mutant htt might be responsible for the gene expression alterations observed in human HD brain. C1 Univ British Columbia, Womens & Childrens Hosp, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC V5H 4H4, Canada. Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Olson, JM (reprint author), Fred Hutchinson Canc Res Ctr, D4-100,1100 Fairview Ave N, Seattle, WA 98109 USA. RI Leavitt, Blair/G-1934-2012; Chan, Edmond/A-1940-2013; Hayden, Michael/D-8581-2011 OI Chan, Edmond/0000-0001-9777-0252; Hayden, Michael/0000-0001-5159-1419 FU NIA NIH HHS [AG13617]; NINDS NIH HHS [NS10800, NS16367, NS35711, NS38106, NS38194, NS42157] NR 56 TC 112 Z9 112 U1 0 U2 0 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 AUG 15 PY 2002 VL 11 IS 17 BP 1939 EP 1951 DI 10.1093/hmg/11.17.1939 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 582MX UT WOS:000177356600004 PM 12165556 ER PT J AU Osborne, CK Pippen, J Jones, SE Parker, LM Ellis, M Come, S Gertler, SZ May, JT Burton, G Dimery, I Webster, A Morris, C Elledge, R Buzdar, A AF Osborne, CK Pippen, J Jones, SE Parker, LM Ellis, M Come, S Gertler, SZ May, JT Burton, G Dimery, I Webster, A Morris, C Elledge, R Buzdar, A TI Double-blind, Randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: Results of a North American trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURGICAL-ADJUVANT-BREAST; ANTIESTROGEN ICI-182780; FUNCTIONAL ASSESSMENT; PURE ANTIESTROGEN; TAMOXIFEN; RESISTANT; TOREMIFENE AB Purpose: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment. Patients and Methods: in this double-blind, double-dummy, parallel-group study, postmenopausal patients were randomized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rate, duration of response (DOR), and tolerability. Results: Patients (n = 400) were followed for a median period of 16.8 months. Fulvestrant was as effective as anastrozole in terms of TTP (hazard ratio, 0.92; 95.14% confidence interval [CI], 0.74 to 1.14; P = .43); median TTP was 5.4 months with fulvestrant and 3.4 months with anastrozole. OR rates were 17.5% with both treatments. Clinical benefit rates (complete response + partial response + stable disease greater than or equal to 24 weeks) were 42.2% for fulvestrant and 36.1% for anastrozole (95% CI, -4.00% to 16.41%, P = .26). In responding patients, median DOR (from randomization to progression) was 19.0 months for fulvestrant and 10.8 months for anastrozole. Using all patients, DOR was significantly greater for fulvestrant compared with anastrozole, the ratio of average response durations was 1.35 (95% CI, 1.10 to 1.67; P < 0.01). Both treatments were well tolerated. Conclusion: Fulvestrant was at least as effective as anastrozole, with efficacy end points slightly favoring fulvestrant. Fulvestrant represents an additional treatment option for postmenopausal women with advanced breast cancer whose disease progresses on tomoxifen therapy. (C) 2002 by American Society of Clinical Oncology. C1 Methodist Hosp, Breast Ctr, Baylor Coll Med, Houston, TX 77030 USA. MD Anderson Canc Ctr, Houston, TX USA. Baylor Sammons Canc Ctr, Dallas, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Lombardi Canc Ctr, Washington, DC USA. Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. Haematol Oncol Assoc VA Ltd, Richmond, VA USA. Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. AstraZeneca, Macclesfield, Cheshire, England. RP Osborne, CK (reprint author), Baylor Coll Med, Breast Ctr, 1 Baylor Plaza,MS 600, Houston, TX 77030 USA. NR 17 TC 355 Z9 366 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 15 PY 2002 VL 20 IS 16 BP 3386 EP 3395 DI 10.1200/JCO.2002.10.058 PG 10 WC Oncology SC Oncology GA 584NM UT WOS:000177473800005 PM 12177098 ER PT J AU Kang, ES Iacomini, J AF Kang, ES Iacomini, J TI Induction of central deletional T cell tolerance by gene therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SKIN ALLOGRAFT-REJECTION; RETROVIRAL TRANSDUCTION; CD4+8+ THYMOCYTES; BONE-MARROW; LYMPHOCYTES; ANTIGEN; AUTOIMMUNITY; PROLONGATION; INVIVO; MICE AB Transgenic mice expressing an alloreactive TCR specific for the MHC class I Ag K-b were used to examine the mechanism by which genetic engineering of bone marrow induces T cell tolerance. Reconstitution of lethally irradiated mice with bone marrow infected with retroviruses carrying the MHC class I gene H-2K(b) resulted in lifelong expression of K-b on bone marrow-derived cells. While CD8 T cells expressing the transgenic TCR developed in control mice reconstituted with mock-transduced bone marrow, CD8 T cells expressing the transgenic TCR failed to develop in mice reconstituted with H-2K(b) transduced bone marrow. Analysis of transgene-expressing CD8 T cells in the thymus and periphery of reconstituted mice revealed that CD8 T cells expressing the transgenic TCR underwent negative selection in the thymus of mice reconstituted with K-b transduced bone marrow. Negative selection induced by gene therapy resulted in tolerance to K-b. Thus, genetic engineering of bone marrow can be used to alter T cell education in the thymus by inducing negative selection. C1 Massachusetts Gen Hosp, Transsplantat Biol Res Ctr, MGH E, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E, Bldg 149,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [R01 AI43619] NR 30 TC 35 Z9 36 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2002 VL 169 IS 4 BP 1930 EP 1935 PG 6 WC Immunology SC Immunology GA 582RW UT WOS:000177365800035 PM 12165518 ER PT J AU Heller, S AF Heller, S TI Application of physiological genomics to the study of hearing disorders SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Review ID OUTER HAIR-CELLS; COCHLEAR STRIA VASCULARIS; LANGE-NIELSEN SYNDROME; INNER-EAR; POTASSIUM CHANNEL; SENSORINEURAL DEAFNESS; DOMINANT DEAFNESS; BARTTER-SYNDROME; MARGINAL CELLS; K+ SECRETION AB Although the biophysical principles of how the ear operates are reasonably wen understood, little is known about the specific genes that confer normal function to the inner ear. Nevertheless, the recent implementation of genomic tools has led to extraordinary progress in the identification of mutated genes that cause non-syndromic and syndromic forms of deafness. Part of this success is directly related to the sequencing of the human and mouse genomes and improved gene annotation methods. This review discusses how physiological genomic tools, such as genomic databases, expressed sequence tag databases and DNA arrays have been applied to find candidate genes for important molecular processes in the inner ear. It also illustrates, using the discovery of genes encoding essential components of cochlear K(+) homeostasis as an example, how the combination of physiological genomic tools with physiological and morphological information has led to an in-depth understanding of cochlear ion homeostasis. Finally, it discusses how the use of applied genomic tools, such as gene arrays, will further advance our knowledge of how the inner ear works, develops, ages and regenerates. C1 Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Heller, S (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM hellers@epl.meei.harvard.edu NR 72 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 15 PY 2002 VL 543 IS 1 BP 3 EP 12 DI 10.1113/jphysiol.2002.018911 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 590WW UT WOS:000177848300002 PM 12181277 ER PT J AU Tyor, WR Avgeropoulos, N Ohlandt, G Hogan, EL AF Tyor, WR Avgeropoulos, N Ohlandt, G Hogan, EL TI Treatment of spinal cord impact injury in the rat with transforming growth factor-beta SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE spinal cord injury; rats; mononuclear phagocytes; cytokines; transforming growth factor-beta ID TUMOR-NECROSIS-FACTOR; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TRAUMATIC INJURY; FACTOR-ALPHA; TNF-ALPHA; TGF-BETA; BRAIN; EXPRESSION; GROWTH-FACTOR-BETA-1; CYTOKINES AB To investigate the contribution of cytokines, proinflammatory TNF-alpha and inhibitory TGF-beta, to spinal cord injury (SCI) in a rat model, two studies were performed using adult Sprague-Dawley rats which were injured at T9/T10. In the first study, rats were sacrificed at 1, 6, 24, 96 and 168 h after SCI for immunocytochemistry of coronal sections for the presence of mononuclear phagocytes, astrocytes, TNF-alpha and TGF-beta, among other markers. From intervening frozen sections, RNA was extracted for semiquantitative polymerase chain reaction (RTPCR) analysis of TNF-alpha and TGF-beta. In the second experiment, rats were treated with intravenous TGF-beta 30 min after injury and sacrificed at 6 and 48 h after injury. Spinal cord sections were immunocytochemically stained and RNA extracted for semiquantitative PCR as mentioned above, as well as quantitation of lesion volume. There were increases in mononuclear phagocytes and astrocytes, as early as 1 h after SCI, with steady progression over 168 h after injury. TNF-alpha and TGF-beta was produced locally by mononuclear phagocytes and astrocytes. There was an 18-h delay in peak mRNA production of TGF-beta compared to TNF-alpha. The treatment of SCI rats with TGF-beta reduced lesion volume by 50% at 48 h and this was associated with decreased accumulation of mononuclear phagocytes in and around the injury site. This reduction of mononuclear phagocyte numbers around the site of trauma would reduce their contribution to secondary injury. Published by Elsevier Science B.V. C1 Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Tyor, WR (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NINDS NIH HHS [NS 31767] NR 28 TC 52 Z9 61 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD AUG 15 PY 2002 VL 200 IS 1-2 BP 33 EP 41 AR PII S0022-510X(02)00113-2 DI 10.1016/S0022-510X(02)00113-2 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 584FY UT WOS:000177457600005 PM 12127673 ER PT J AU Adamec, E Murrell, JR Takao, M Hobbs, W Nixon, RA Ghetti, B Vonsattel, JP AF Adamec, E Murrell, JR Takao, M Hobbs, W Nixon, RA Ghetti, B Vonsattel, JP TI P301L tauopathy: confocal immunofluorescence study of perinuclear aggregation of the mutated protein SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Tau protein; Tauopathy; mutation; frontotemporal dementia; immunohistochemistry; confocal microscopy ID FRONTOTEMPORAL DEMENTIA; TAU-GENE; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISORDERS; PICKS-DISEASE; MUTATIONS; CALPAIN; PARKINSONISM; FTDP-17; CHROMOSOME-17 AB The clinical and neuropathological features in the P301L tauopathy have been described in several kindreds. In this study, we present findings in two previously unreported patients, evaluated both genetically, neuropathologically, and with multiparametric confocal immunofluorescence. The patients were female, with age 65 and 75 years old, respectively. Both exhibited clinical symptoms of frontotemporal dementia (FTD). Marked atrophy of the frontal and temporal lobes with moderate atrophy of the remaining cerebral and brain stem structures was present. The substantia nigra was pale. The atrophic neocortical regions exhibited neuronal loss, marked gliosis, status spongiosus, and occasional ballooned neurons. By light microscopy, the most striking findings were argyrophilic perinuclear rings, frequently with an attached small inclusion (mini Pick-like body), especially prominent in dentate granule cells; entorhinal and temporal cortices, and to a lesser extent in CA1. These structures were immunopositive for tau protein (Tau-2, AT-8, PHF-1, MC-1). Numerous astrocytic plaques, tuft-shaped astrocytes, coiled bodies, and dystrophic neurites were also present. Confocal immunofluorescence with a P301L-specific antibody directly demonstrated the presence of the mutated protein in the PHF-1 positive aggregates. The mutated tau protein (4-repeat tau) was detected in the mini Pick-like bodies, indicating an important biochemical difference between these inclusions and classical Pick bodies (3-repeat tau). Additionally, since 4-repeat tau protein is not normally present in dentate granule cells, this result also suggests an abnormality in the mRNA splicing mechanisms. The structural features of the involvement of proteolytic systems in this tauopathy were assessed by immunohistochemistry for the active form of calpain II (C-27) and ubiquitin. Colocalization of PHF-1 positive aggregates with C-27 points to the possible involvement of calpain in tau protein hyperphosphorylation. Absence of immunostaining for ubiquitin indicates possible dysfunction of the ubiquitin-proteasome system in this tauopathy. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, McLean Hosp, Sch Med, Labs Mol Neurosci,Mailman Res Ctr,Dept Psychiat, Belmont, MA 02478 USA. Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. NYU, Sch Med, Dept Psychiat, Orangeburg, NY 10962 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. NYU, Sch Med, Dept Cell Biol, Orangeburg, NY 10962 USA. Columbia Univ, Columbia Presbyterian Med Ctr, Dept Pathol, New York, NY 10032 USA. RP Adamec, E (reprint author), Harvard Univ, McLean Hosp, Sch Med, Labs Mol Neurosci,Mailman Res Ctr,Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. FU NIA NIH HHS [AG00764, AG17617, AG10133, AG05134]; NIMH NIH HHS [MH/NS 31862] NR 50 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD AUG 15 PY 2002 VL 200 IS 1-2 BP 85 EP 93 AR PII S0022-510X(02)00150-8 DI 10.1016/S0022-510X(02)00150-8 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 584FY UT WOS:000177457600014 PM 12127682 ER PT J AU Lin, J Wu, H Tarr, PT Zhang, CY Wu, ZD Boss, O Michael, LF Puigserver, P Isotani, E Olson, EN Lowell, BB Bassel-Duby, R Spiegelman, BM AF Lin, J Wu, H Tarr, PT Zhang, CY Wu, ZD Boss, O Michael, LF Puigserver, P Isotani, E Olson, EN Lowell, BB Bassel-Duby, R Spiegelman, BM TI Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres SO NATURE LA English DT Article ID SKELETAL-MUSCLE; FIBER-TYPE; MITOCHONDRIAL BIOGENESIS; COACTIVATOR PGC-1; CALCINEURIN; EXPRESSION; ELEMENTS; PATHWAY; MEF2; GENE AB The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres(1). We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma coactivator-1 (PGC-1alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism(2-4).We show here that PGC-1alpha is expressed preferentially in muscle enriched in type I fibres. When PGC-1alpha is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1alpha transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1alpha activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1alpha is a principal factor regulating muscle fibre type determination. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 27 TC 1333 Z9 1401 U1 15 U2 110 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 15 PY 2002 VL 418 IS 6899 BP 797 EP 801 DI 10.1038/nature00904 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583UF UT WOS:000177428000044 PM 12181572 ER PT J AU Demetri, GD von Mehren, M Blanke, CD Van den Abbeele, AD Eisenberg, B Roberts, PJ Heinrich, MC Tuveson, DA Singer, S Janicek, M Fletcher, JA Silverman, SG Silberman, SL Capdeville, R Kiese, B Peng, B Dimitrijevic, S Druker, BJ Corless, C Fletcher, CDM Joensuu, H AF Demetri, GD von Mehren, M Blanke, CD Van den Abbeele, AD Eisenberg, B Roberts, PJ Heinrich, MC Tuveson, DA Singer, S Janicek, M Fletcher, JA Silverman, SG Silberman, SL Capdeville, R Kiese, B Peng, B Dimitrijevic, S Druker, BJ Corless, C Fletcher, CDM Joensuu, H TI Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; C-KIT; STI-571; GROWTH; AMPLIFICATION; RESISTANCE; STI571; ST1571; CELLS AB Background Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors. Methods We conducted an open-label, randomized, multicenter trial to evaluate the activity of imatinib in patients with advanced gastrointestinal stromal tumor. We assessed antitumor response and the safety and tolerability of the drug. Pharmacokinetics were assessed in a subgroup of patients. Results A total of 147 patients were randomly assigned to receive 400 mg or 600 mg of imatinib daily. Overall, 79 patients (53.7 percent) had a partial response, 41 patients (27.9 percent) had stable disease, and for technical reasons, response could not be evaluated in 7 patients (4.8 percent). No patient had a complete response to the treatment. The median duration of response had not been reached after a median follow-up of 24 weeks after the onset of response. Early resistance to imatinib was noted in 20 patients (13.6 percent). Therapy was well tolerated, although mild-to-moderate edema, diarrhea, and fatigue were common. Gastrointestinal or intraabdominal hemorrhage occurred in approximately 5 percent of patients. There were no significant differences in toxic effects or response between the two doses. Imatinib was well absorbed, with pharmacokinetics similar to those reported in patients with chronic myeloid leukemia. Conclusions Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor. Inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinal stromal tumors, which resist conventional chemotherapy. C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Oregon Hlth & Sci Univ, Portland, OR USA. Oregon Hlth Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. Univ Turku, Turku, Finland. Novartis Oncol, Basel, Switzerland. Univ Helsinki, Helsinki, Finland. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, SW 530,44 Binney St, Boston, MA 02115 USA. NR 25 TC 2424 Z9 2593 U1 16 U2 110 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 AUG 15 PY 2002 VL 347 IS 7 BP 472 EP 480 DI 10.1056/NEJMoa020461 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 587ZM UT WOS:000177674400003 PM 12181401 ER PT J AU Ryan, ET Wilson, ME Kain, KC AF Ryan, ET Wilson, ME Kain, KC TI Current concepts - Illness after international travel SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CLINICAL PRESENTATION; IMPORTED MALARIA; NONENDEMIC POPULATIONS; DEVELOPING-COUNTRIES; PERSISTENT DIARRHEA; HEALTH-PROBLEMS; UNITED-STATES; FEVER; TROPICS; RISK C1 Massachusetts Gen Hosp, Trop & Geog Med Ctr, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mt Auburn Hosp, Travel Resource Ctr, Div Infect Dis, Cambridge, MA 02238 USA. Univ Toronto, Toronto Gen Hosp, Div Infect Dis, Ctr Travel & Trop Med, Toronto, ON M5G 1L7, Canada. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Trop & Geog Med Ctr, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI-40725, R01 AI040725]; NICHD NIH HHS [HD-39165, U01 HD039165] NR 60 TC 146 Z9 148 U1 2 U2 9 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 AUG 15 PY 2002 VL 347 IS 7 BP 505 EP 516 DI 10.1056/NEJMra020118 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 587ZM UT WOS:000177674400008 PM 12181406 ER PT J AU Fishman, JA AF Fishman, JA TI BK virus nephropathy - Polyomavirus adding insult to injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ORGAN-TRANSPLANT RECIPIENTS; JC VIRUS; INFECTIONS; DNA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 16 TC 98 Z9 100 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 AUG 15 PY 2002 VL 347 IS 7 BP 527 EP 530 DI 10.1056/NEJMe020076 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 587ZM UT WOS:000177674400011 PM 12181409 ER PT J AU Miyoshi, K Rosner, A Nozawa, M Byrd, C Morgan, F Landesman-Bollag, E Xu, X Seldin, DC Schmidt, EV Taketo, MM Robinson, GW Cardiff, RD Hennighausen, L AF Miyoshi, K Rosner, A Nozawa, M Byrd, C Morgan, F Landesman-Bollag, E Xu, X Seldin, DC Schmidt, EV Taketo, MM Robinson, GW Cardiff, RD Hennighausen, L TI Activation of different Wnt/beta-catenin signaling components in mammary epithelium induces transdifferentiation and the formation of pilar tumors SO ONCOGENE LA English DT Article DE Wnt signaling; beta-catenin activation; Int2/Fgf3; cytokeratin expression; pilar tumor; transdifferentiation ID PROTEIN-KINASE CK2; BETA-CATENIN; TRANSGENIC MICE; CYCLIN D1; FUNCTIONAL INTERACTION; HAIR FOLLICLE; FEMALE MICE; GENE; GLAND; EXPRESSION AB The Wnt/beta-catenin signaling pathway controls cell fate and neoplastic transformation. Expression of an endogenous stabilized beta-catenin (DeltaE3 beta-catenin) in mammary epithelium leads to the transdifferentiation into epidermis- and pilar-like structures. Signaling molecules in the canonical Wnt pathway upstream from P-catenin induce glandular tumors but it is not clear whether they also cause squamous transdifferentiation. To address this question we have now investigated mammary epithelium from transgenic mice that express activating molecules of the Wnt pathway: Wnt10b, Int2/Fgf3, CK2alpha, DeltaE3 beta-catenin, Cyclin D1, and dominant negative (dn) GSK3beta. Cytokeratin 5 (CK5), which is expressed in both mammary myoepithelium and epidermis, and the epidermis-specific CK1 and CK6 were used as differentiation markers. Extensive squamous metaplasias and widespread expression of CK1 and CK6 were observed in DeltaE3 beta-catenin transgenic mammary tissue. Wnt10b and Int2 transgenes also induced squamous metaplasias, but expression of CK1 and CK6 was sporadic. While CK5 expression in Wnt I Ob transgenic tissue was still confined to the lining cell layer, its expression in Int2 transgenic tissue was completely disorganized. In contrast, cytokeratin expression in CK2alpha dnGSK3beta and Cyclin D1 transgenic mammary tissues was similar to that in DeltaE3 beta-catenin tissue. In support of transdifferentiation, expression of hard keratins specific for hair and nails was observed in pilar tumors. These results demonstrate that the activation of Wnt signaling components in mammary epithelium induces not only glandular tumors but also squamous differentiation, possibly by activating LEF-1, which is expressed in normal mammary epithelium. C1 NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Univ Tokushima, Sch Dent, Dept Biochem, Tokushima 7708504, Japan. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Boston Univ, Med Ctr, Boston, MA 02118 USA. McLaughlin Res Inst, Great Falls, MT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Kyoto Univ, Grad Sch Med, Kyoto, Japan. RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bldg 8,Room 101,8 Ctr Dr, Bethesda, MD 20892 USA. RI Robinson, Gertraud/I-2136-2012 FU NCRR NIH HHS [U42 RR14905]; NIEHS NIH HHS [P01 ES11624] NR 46 TC 85 Z9 90 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 15 PY 2002 VL 21 IS 36 BP 5548 EP 5556 DI 10.1038/sj.onc.1205686 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 583ZM UT WOS:000177442000004 PM 12165853 ER PT J AU Wang, N Lee, JM Tobiasch, E Csizmadia, E Smith, NR Gollackes, B Robson, SC Bach, FH Lin, Y AF Wang, N Lee, JM Tobiasch, E Csizmadia, E Smith, NR Gollackes, B Robson, SC Bach, FH Lin, Y TI Induction of xenograft accommodation by modulation of elicited antibody responses SO TRANSPLANTATION LA English DT Article ID PORCINE ENDOTHELIAL-CELLS; LONG-TERM SURVIVAL; IN-VITRO ACCOMMODATION; INDUCED LUNG INJURY; NF-KAPPA-B; HEME OXYGENASE-1; HAMSTER HEARTS; NITRIC-OXIDE; CARDIAC XENOGRAFTS; NATURAL ANTIBODIES AB Background. We have established that the timing of splenectomy influences the magnitude of the xenoreactive antibody (XAb) response and thus hamster heart survival in cyclosporine (CyA)-treated rats. This model has been used to test our hypothesis that modulation of XAb responses without perturbation of complement may influence the development of graft accommodation. Methods. Pretransplantation splenectomy (day -1/day 0) fully abrogated anti-graft IgM response, whereas a delayed procedure (day 1/day 2) caused significantly delayed (3-4 days) and decreased levels (two- to threefold) of XAb. Both interventions resulted in long-term graft survival. After surviving for 7 or more days, xenografts in CyA-treated rats with post-, but not pre-, transplantation splenectomy were also resistant to exogenous anti-graft XAb. Such grafts meet the criteria for accommodation. Accommodating hearts displayed progressive and increasing expression of protective genes, such as heme oxygense (HO)-1 and A20, in endothelial cells and smooth muscle cells. Results. Our results suggest that XAb responses may influence the kinetics of accommodation development possibly by promoting protective gene expression. This hypothesis was directly tested in vitro. Pretreatment of porcine aortic endothelial cells with sublytic amounts of baboon anti-pig serum for 24 hr induced HO-1 expression; this was associated with cell resistance to lytic amounts of such serum. Overexpression of HO-1 by adenoviral-mediated gene transfer in porcine aortic endothelial cells resulted in similar protective effects. Conclusions. Delayed and relatively low levels of XAb IgM promote expression of protective genes in the graft and thereby aid in the progress of accommodation. Expression of HO-1 protects xenoserum-mediated endothelial cell destruction. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Bach, FH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, 99 Brookline Ave,Room 370, Boston, MA 02215 USA. OI LEE, JANG-MING/0000-0001-9727-227X FU NHLBI NIH HHS [HL 58688] NR 63 TC 22 Z9 27 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 AUG 15 PY 2002 VL 74 IS 3 BP 334 EP 345 AR UNSP 0041-1337/02/7403-334/0 DI 10.1097/00007890-200208150-00008 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 584YH UT WOS:000177496000008 PM 12177611 ER PT J AU Ohuchi, H Madsen, JC Neragi-Miandoab, S Vlahakes, GJ AF Ohuchi, H Madsen, JC Neragi-Miandoab, S Vlahakes, GJ TI A novel technique for en bloc, vascularized, composite thymic, and cardiac co-transplantation. SO TRANSPLANTATION LA English DT Article ID EPITHELIUM; TOLERANCE; RATS AB Background. A surgical technique for co-transplantation of fully vascularized thymus and heart potentially applicable to the clinical setting has not been developed and is the subject of this article. Methods. Vascularized right lobe of the thymus was transplanted heterotopically with the heart as a composite graft in rats. This co-transplantation technique was developed and assessed, and viability of the grafted thymus was evaluated histologically. Results. Surgical mortality was identical to isolated heart transplantation, and all grafted hearts functioned well. Histology of the thymic grafts at explantation revealed viable thymus with preservation of normal thymic microarchitecture. Conclusion. We developed a novel technique to create a composite graft in which fully vascularized and viable thymus was harvested en bloc and co-transplanted with a donor heart allograft. C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Vlahakes, GJ (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,BUL 119, Boston, MA 02114 USA. NR 9 TC 6 Z9 7 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 AUG 15 PY 2002 VL 74 IS 3 BP 403 EP 405 AR UNSP 0041-1337/02/7403-403/0 DI 10.1097/00007890-200208150-00018 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 584YH UT WOS:000177496000018 PM 12177621 ER PT J AU Altarescu, G Sun, M Moore, DF Smith, JA Wiggs, EA Solomon, BI Patronas, NJ Frei, KP Gupta, S Kaneski, CR Quarrell, OW Slaugenhaupt, SA Goldin, E Schiffmann, R AF Altarescu, G Sun, M Moore, DF Smith, JA Wiggs, EA Solomon, BI Patronas, NJ Frei, KP Gupta, S Kaneski, CR Quarrell, OW Slaugenhaupt, SA Goldin, E Schiffmann, R TI The neurogenetics of mucolipidosis type IV SO NEUROLOGY LA English DT Review ID NATURAL-HISTORY; CORPUS-CALLOSUM; MUTATIONS; MRI; IDENTIFICATION; MORPHOLOGY; DISEASE; CHANNEL; PATIENT AB Background: Mucolipidosis type IV (MLIV) is an autosomal recessive disease caused by mutations in the MCOLN1 gene that codes for mucolipin, a member of the transient receptor potential (TRP) gene family. Objective: To comprehensively characterize the clinical and genetic abnormalities of MLIV. Methods: Twenty-eight patients with MLIV, aged 2 to 25 years, were studied. Ten returned for follow-up every I to 2 years for up to 5 years. Standard clinical, neuroimaging, neurophysiologic, and genetic techniques were used. Results: All patients had varying degrees of corneal clouding, with progressive optic atrophy and retinal dystrophy. Twenty-three patients had severe motor and mental impairment. Motor function deteriorated in three patients and remained stable in the rest. All had a constitutive achlorhydria with elevated plasma gastrin level, and 12 had iron deficiency or anemia. Head MRI showed consistent characteristic findings of a thin corpus callosum and remained unchanged during the follow-up period. Prominent abnormalities of speech, hand usage, and swallowing were also noted. Mutations in the MCOLN1 gene were present in all patients. Correlation of the genotype with the neurologic handicap and corpus callosum dysplasia was found. Conclusions: MLIV is both a developmental and a degenerative disorder. The presentation as a cerebral palsy-like encephalopathy may delay diagnosis. C1 NIH, Warren G Magnuson Clin Ctr, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Speech Language Pathol Sect, Dept Rehabil Med, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Sheffield Childrens Hosp, N Trent Genet Serv, Sheffield, S Yorkshire, England. RP Schiffmann, R (reprint author), NIH, Warren G Magnuson Clin Ctr, Dev & Metab Neurol Branch, 9000 Rockville Pike,Bldg 10,Rm 3D03, Bethesda, MD 20892 USA. OI Kaneski, Christine/0000-0003-1453-2502 FU NINDS NIH HHS [NS 39995] NR 38 TC 88 Z9 90 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 13 PY 2002 VL 59 IS 3 BP 306 EP 313 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 582EB UT WOS:000177335800004 PM 12182165 ER PT J AU Weaver, JD Huang, MH Albert, M Harris, T Rowe, JW Seeman, TE AF Weaver, JD Huang, MH Albert, M Harris, T Rowe, JW Seeman, TE TI Interleukin-6 and risk of cognitive decline - MacArthur studies of successful aging SO NEUROLOGY LA English DT Article ID LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; TRANSGENIC MICE; CEREBRAL OVEREXPRESSION; DENTATE GYRUS; COMMUNITY; BRAIN; PERFORMANCE; CYTOKINES AB Objective: To investigate whether plasma interleukin-6 (IL-6) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population-based sample of nondisabled elderly people. Methods: A prospective cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted. Regression modeling was used to investigate whether baseline IL-6 levels (classified by tertiles) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 (2.5-year follow-up) and from 1988 to 1995 (7-year follow-up). Results: Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function (i.e., scores below the median), independent of demographic status, social status, health and health behaviors, and other physiologic variables (odds ratio [OR] = 1.46; 95% CI: 0.97, 2.20). At 2.5 years, those in both the second tertile of IL-6 (OR = 2.21; 95% CI: 1.44, 3.42) and the third tertile (OR = 2.03; 95% Cl: 1.30, 3.19) were at increased risk of cognitive decline even after adjusting for all confounders. At 7 years of follow-up, only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition (OR = 1.90; 95% CI: 1.14, 3.18) after adjustment for all confounders. Conclusions: The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function. These findings are consistent with the hypothesized relationship between brain inflammation, as measured here by elevated plasma IL-6, and neuropathologic disorders. C1 Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat Gerontol, Boston, MA USA. NIA, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Seeman, TE (reprint author), Univ Calif Los Angeles, Sch Med, Div Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. FU NIA NIH HHS [AG-17056, AG-17265] NR 26 TC 267 Z9 276 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 13 PY 2002 VL 59 IS 3 BP 371 EP 378 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 582EB UT WOS:000177335800013 PM 12177370 ER PT J AU Ganzini, L Johnston, WS Silveira, MJ AF Ganzini, L Johnston, WS Silveira, MJ TI The final month of life in patients with ALS SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; PRACTICE PARAMETER; TERMINAL PHASE; CARE DATABASE; GOOD DEATH; QUALITY AB Objective: To study the health care experiences and palliative care needs of patients with ALS in their final month of life. Methods: Caregivers of decedent patients with ALS completed a single survey focused on the final month of life. They reported the patients' physical and emotional symptoms, preferences for end-of-life care, completion of advance directives, and preparation for death. The caregiver reported which life-sustaining treatments were administered, withheld, or withdrawn; whether the patient was enrolled in hospice; and their own satisfaction with the patient's medical care. Results: Fifty caregivers completed the survey. Caregivers reported that the most common symptoms in the last month of life included difficulty communicating (62%), dyspnea (56%), insomnia (42%), and discomfort other than pain (48%). Pain was both frequent and severe. One-third of caregivers were dissatisfied with some aspect of symptom management. Caregivers reported an advance directive was completed by 88% of patients and the patients' goals of care were honored by 88% of health care practitioners. Two-thirds of patients were enrolled in hospice. Compared to nonhospice patients, hospice patients were significantly more likely to: 1) die in their preferred location; 2) die outside the hospital; and 3) receive morphine. Most caregivers reported that their loved one was at peace, and prepared for and was accepting of death. Conclusions: Caregivers report that many patients with ALS still experience distressing physical symptoms in the last month of life, despite enrollment in hospice. Most patients with ALS, however, anticipate and plan for their deaths and have their wishes respected. C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. Univ Alberta, Div Neurol, Edmonton, AB, Canada. Univ Michigan, Sch Med, VA Hlth Serv Res & Dev Serv, VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Univ Michigan, Sch Med, Bioeth Program, Ann Arbor, MI USA. RP Ganzini, L (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, POB 1034, Portland, OR 97207 USA. RI Silveira, Maria/E-9802-2013; Johnston, Wendy/E-2491-2013 OI Johnston, Wendy/0000-0002-4330-5563 NR 20 TC 61 Z9 62 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 13 PY 2002 VL 59 IS 3 BP 428 EP 431 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 582EB UT WOS:000177335800021 PM 12177378 ER PT J AU Augood, SJ Hollingsworth, Z Albers, DS Yang, L Leung, JC Muller, B Klein, C Breakefield, XO Standaert, DG AF Augood, SJ Hollingsworth, Z Albers, DS Yang, L Leung, JC Muller, B Klein, C Breakefield, XO Standaert, DG TI Dopamine transmission in DYT1 dystonia: A biochemical and autoradiographical study SO NEUROLOGY LA English DT Article ID TORSION DYSTONIA; BINDING; BRAIN AB Indices of dopamine transmission were measured in the postmortem striatum of DYT1 dystonia brains. A significant increase in the striatal 3,4-dihydroxyphenylacetic acid/dopamine ratio was found. Quantitative autoradiography revealed no differences in the density of dopamine transporter or vesicular monoamine transporter-2 binding; however, there was a trend toward a reduction in D, receptor and D-2 receptor binding. One brain with DYT1 parkinsonism was similarly evaluated and marked reductions in striatal dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid content as well as the density of binding of all four dopaminergic ligands were measured. C1 Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY USA. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. RP Augood, SJ (reprint author), Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, CNY 114-2300,114 16th St, Charlestown, MA 02129 USA. OI Standaert, David/0000-0003-2921-8348 FU NICHD NIH HHS [N01 HD 83283]; NINDS NIH HHS [NS 28384, NS 37409] NR 10 TC 77 Z9 80 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 13 PY 2002 VL 59 IS 3 BP 445 EP 448 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 582EB UT WOS:000177335800027 PM 12177384 ER PT J AU Barr, RG Somers, SC Speizer, FE Camargo, CA AF Barr, RG Somers, SC Speizer, FE Camargo, CA TI Patient factors and medication guideline adherence among older women with asthma SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HEALTH SURVEY SF-36; MANAGEMENT; THERAPY; CARE; TESTS; RISK; POOR; HMO AB Background: Asthma guidelines are well established but often followed poorly. Determinants of adherence among older persons may differ from younger persons and have not beers well characterized. Objectives: To assess adherence to asthma medication guidelines among older women with asthma and evaluate predictors of adherence with emphasis on asthma characteristics, comorbid medical conditions, work-related factors, social supports, caregiving, and emotional well-being. Methods: We assessed adherence to the National Asthma Education and Prevention Program medication guidelines among participants in the Nurses' Health Study who reported a physician diagnosis of asthma and reconfirmed the diagnosis on a separate questionnaire, excluding those with chronic obstructive pulmonary disease. Results: Among 121700 participants in the Nurses' Health Study, 5107 reported physician-diagnosed asthma meeting inclusion criteria. Mean +/-SD age was 63 +/- 7 years in 1998. Adherence with asthma medication guidelines was 57% for mild persistent, 55% for moderate persistent, and 32% for severe persistent asthma (P=.001). In multivariate analysis, nonadherence was associated with severe asthma, increasing age, lower socioeconomic status, current smoking, earlier onset of asthma, and number of comorbid medical conditions. Measures of social isolation, caregiving, and emotional well-being were not associated with nonadherence. Conclusions: Asthma is undertreated among older women, even those who are health care professionals. Women with advanced age and severe asthma were particularly at risk. Given that the greatest increase in asthma mortality has occurred among older women, further research is needed to examine physician prescribing patterns and patient beliefs in this vulnerable population. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. RP Camargo, CA (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU BHP HRSA HHS [PE-11001]; NCI NIH HHS [CA-87969]; NHLBI NIH HHS [HL-03533, HL-07427, HL-63841] NR 29 TC 71 Z9 72 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 12 PY 2002 VL 162 IS 15 BP 1761 EP 1768 DI 10.1001/archinte.162.15.1761 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 581GT UT WOS:000177283900013 PM 12153380 ER PT J AU Wu, AG Fujikawa, DG AF Wu, AG Fujikawa, DG TI Effects of AMPA-receptor and voltage-sensitive sodium channel blockade on high potassium-induced glutamate release and neuronal death in vivo SO BRAIN RESEARCH LA English DT Article DE high potassium; microdialysis; cell death; sodium channel; AMPA receptor; tetrodotoxin ID EXCITATORY AMINO-ACIDS; SPINAL-CORD INJURY; EXTRACELLULAR POTASSIUM; SPREADING DEPRESSION; RAT-BRAIN; HIPPOCAMPAL CA1; GLOBAL-ISCHEMIA; CELL-CULTURE; NEUROTOXICITY; ASPARTATE AB High extracellular potassium induces spreading depression-like depolarizations and elevations of extracellular glutamate. Both occur in the penumbra of a focal ischemic infarct, and may be responsible for the spread of cell death from the infarct core to the penumbra. We have modeled this situation with microdialysis of an isotonic high-potassium solution into the normal rat amygdala for 70 min. This elevates extracellular glutamate up to 8-fold or more and produces irreversibly damaged, acidophilic neurons. NMDA-receptor blockade protects neurons and reduces the elevation of extracellular glutamate. Here we investigated the effects of sodium channel blockade with the voltage-sensitive sodium channel blocker tetrodotoxin and the AMPA receptor antagonist 2,3-dihydroxy-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide disodium (NBQX disodium) on high potassium-induced neuronal death and extracellular glutamate elevations. The acidophilic neurons produced are necrotic by ultrastructural examination. Tetrodotoxin, at dialysate concentrations of 33, 330 and 3300 muM (only a small fraction is extracted by tissue), markedly reduced the elevations of glutamate in rat amygdala at nearly all time points during high-potassium perfusion, but it reduced tissue edema only at the highest concentration, and it was neuroprotective only if dialyzed prior to high-potassium microdialysis (at 330 muM concentration). Although both 250 muM (6.2% is extracted by tissue) and 500 muM NBQX reduced elevations of glutamate, neither was neuroprotective, and neuropil edema was not reduced by either concentration. Our results suggest that in vivo, sodium influx through voltage-sensitive sodium channels but not through ligand-gated AMPA receptor channels contributes to high potassium-induced neuronal necrosis. Published by Elsevier Science B.V. C1 VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. Nursing Home Care Unit, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Fujikawa, DG (reprint author), VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab 151B4, Sepulveda Ambulatory Care Ctr, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 43 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 9 PY 2002 VL 946 IS 1 BP 119 EP 129 AR PII S0006-8993(02)02869-X DI 10.1016/S0006-8993(02)02869-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 591NH UT WOS:000177886500013 PM 12133601 ER PT J AU Kinoshita, A Whelan, CM Berezovska, O Hyman, BT AF Kinoshita, A Whelan, CM Berezovska, O Hyman, BT TI The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-SECRETASE; NUCLEAR TRANSLOCATION; INTRACELLULAR DOMAIN; NOTCH; PRESENILIN; FE65; MUTATIONS; CLEAVAGE; NEURONS; PROTEOLYSIS AB The amyloid precursor protein (APP), a large glycoprotein highly expressed in neurons, is cleaved in its intramembranous domain by gamma secretase to generate amyloid-beta and a free carboxyl-terminal intracellular fragment (APP-CT), which has previously been suggested to interact with the adapter protein Fe65 and the histone acetyltransferase Tip60. An identical gamma secretase activity mediates cleavage of Notch, releasing an intracellular signaling domain that translocates to the nucleus. We examined the effect of an ectopically expressed 58-amino acid APP-CT fragment (APP-C58) on human H4 neuroglioma cells. We demonstrate by confocal microscopy and fluorescence resonance energy transfer analysis that APP-C58 translocates to the nucleus and forms a complex in the nucleus with the Tip60, independent of interactions with Fe65. APP-C58 transfected H4 cells undergo apoptosis within 48-72 h, marked by nuclear blebbing, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, and blockade by a caspase inhibitor. When nuclear access of APP-C58 is prevented by fusing with a strong membrane-targeting farnesylation domain, apoptosis is blocked. APP-C58-induced apoptosis was markedly enhanced by co-transfection with wild type Tip60 and decreased by mutant Tip60 lacking histone acetyltransferase activity, suggesting that Tip60 mediates APP-CT-induced cell death. Thus, gamma secretase cleavage of APP may contribute to Alzheimer's disease-related neurodegencration in two ways: release of amyloid-beta and liberation of a bioactive carboxyl-terminal domain from membrane-bound APP. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Dept Neurol, Alzheimers Unit, 114 16th St,CAGN 2009, Charlestown, MA 02129 USA. FU NIA NIH HHS [P01 AG15379, AG12406] NR 29 TC 101 Z9 106 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 9 PY 2002 VL 277 IS 32 BP 28530 EP 28536 DI 10.1074/jbc.M203372200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 582GX UT WOS:000177342600025 PM 12032152 ER PT J AU Martin-Rehrmann, MD Cho, HS Rebeck, GW AF Martin-Rehrmann, MD Cho, HS Rebeck, GW TI Lack of association of two lipoprotein lipase polymorphisms with Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE case-control; genetics; risk factor; apolipoprotein E receptor; low-density lipoprotein receptor-related protein ID RECEPTOR-RELATED PROTEIN; GENE EXON-3 POLYMORPHISM; APOLIPOPROTEIN-E; HEART-DISEASE; PLASMA-LIPIDS; METAANALYSIS; METABOLISM; MUTATIONS AB A recent genetic study demonstrated associations between an altered risk of Alzheimer's disease (AD) and two polymorphisms in the lipoprotein lipase (LPL) gene, Asn291Ser and Ser447Ter. LPL immunostains senile plaques, and is a ligand of the low-density lipoprotein receptor-related protein (LRP), a major apolipoprotein E (apoE) receptor. LPL increases the cellular uptake of apoE via LRP, and polymorphisms in LPL alter its ability to mediate apoE-LRP interactions, with potential implications for AD pathogenesis. Here, we tested the genetic association of LPL with AD in a case-control study. For the Asn291Ser polymorphism, we analyzed 277 individuals (141 AD, 136 control) and found no significant difference in allele frequencies between the AD and control groups. For the Ser447Ter polymorphism, we analyzed 187 individuals (108 AD, 79 control) and again found no significant difference in allele frequencies between the AD and control groups. Thus, our study does not support associations between AD and two common polymorphisms in LPL. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, 149 16th St, Charlestown, MA 02129 USA. FU NCHM CDC HHS [HM31862]; NIA NIH HHS [AG14473, AG05134] NR 20 TC 16 Z9 16 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 AUG 9 PY 2002 VL 328 IS 2 BP 109 EP 112 AR PII S0304-3940(02)00511-6 DI 10.1016/S0304-3940(02)00511-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 585JA UT WOS:000177520600009 PM 12133567 ER PT J AU Faraone, SV Skol, AD Tsuang, DW Bingham, S Young, KA Prabhudesai, S Haverstock, SL Mena, F Menon, ASK Bisset, D Pepple, J Sautter, F Baldwin, C Weiss, D Collins, J Keith, T Boehnke, M Tsuang, MT Schellenberg, GD AF Faraone, SV Skol, AD Tsuang, DW Bingham, S Young, KA Prabhudesai, S Haverstock, SL Mena, F Menon, ASK Bisset, D Pepple, J Sautter, F Baldwin, C Weiss, D Collins, J Keith, T Boehnke, M Tsuang, MT Schellenberg, GD TI Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE chromosome 13; schizophrenia; linkage; genetics ID SUSCEPTIBILITY LOCI; GENOME SCAN; DIAGNOSTIC INTERVIEW; BIPOLAR-DISORDER; 13Q14.1-Q32; CONSORTIUM; PEDIGREES; FAMILIES; REGIONS; PROGRAM AB Several prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European-American families (n = 62, 37%), but a substantial proportion were African-American kindreds (n = 60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the 13q32 region were genotyped and the data analyzed using semiparametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z-score of 2.57; P = 0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cM of the peak reported by Brzustowicz et al. Published 2002 Wiley-Liss, Inc. C1 Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Harvard Univ, Massachusetts Mental Hlth Ctr, Dept Psychiat, Sch Med, Boston, MA USA. Inst Psychiat Epidemiol & Genet, Boston, MA USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. Vet Affairs Med Ctr, Waco, TX USA. Vet Affairs Med Ctr, Danville, IL USA. Vet Affairs Med Ctr, Augusta, GA USA. Vet Affairs Med Ctr, Tuskegee, AL USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Vet Affairs Med Ctr, New Orleans, LA USA. Vet Affairs Med Ctr, Northport, NY USA. Genome Therapeut Corp, Waltham, MA USA. RP Faraone, SV (reprint author), Harvard Univ, Suite 255,750 Washington St, S Easton, MA 02375 USA. RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Faraone, Stephen/0000-0002-9217-3982 NR 26 TC 28 Z9 30 U1 1 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 AUG 8 PY 2002 VL 114 IS 6 BP 598 EP 604 DI 10.1002/ajmg.10601 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 579NU UT WOS:000177185400002 PM 12210272 ER PT J AU Devlin, B Bennett, P Cook, RH Dawson, G Gonen, D Grigorenko, EL McMahon, W Pauls, D Smith, M Spence, MA Schellenberg, GD AF Devlin, B Bennett, P Cook, RH Dawson, G Gonen, D Grigorenko, EL McMahon, W Pauls, D Smith, M Spence, MA Schellenberg, GD CA CPEA Genetics Network TI No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE autism; HOXA1; Asperger syndrome; pervasive developmental disorder; genetic association; autistic disorder ID PERVASIVE DEVELOPMENTAL DISORDERS; FETAL VALPROATE SYNDROME; FAMILY HISTORY; SPECTRUM DISORDERS; SUSCEPTIBILITY; DISEQUILIBRIUM; GENE; DUPLICATION; INDIVIDUALS; ASSOCIATION AB A recent study by Ingram et al. [2000b: Teratology 62:393-405] suggests a (His)73(Arg) polymorphism (A:G) in HOXA1 contributes substantially to a liability for autism. Using 68 individuals diagnosed with Autism Spectrum Disorders, they found a significant dearth of G homozygotes and biased transmission of G alleles from parents to affected offspring, especially from mothers. Because the connection between HOXA1 and liability to autism is compelling, we attempted to replicate their finding using a larger, independent sample from the Collaborative Programs of Excellence in Autism (CPEA) network. In our data, genotype frequencies conform to Hardy-Weinberg equilibrium; allele transmissions meet Mendelian expectations; and there is no obvious sex-biased allele transmission. Based on our sample size, calculations suggest that we would have at least 95% power to detect linkage and association even if the A:G polymorphism were to account for only 1% of the heritability of autism. Therefore, although we cannot exclude the possibility that the samples in the two studies are intrinsically different, our data from our sample argue against a major role for HOXA1 (His)73(Arg) in liability to autism. (C) 2002 Wiley-Liss, Inc. C1 Vet Affairs Med Ctr, Seattle, WA 98108 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Utah, Dept Psychiat, Div Child & Adolescent Psychiat, Salt Lake City, UT USA. Univ Chicago, Dept Obstet, Lab Dev Neurosci, Dept Psychiat, Chicago, IL 60637 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Psychol, New Haven, CT 06510 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Unit Psychiat & Neurodev Genet, Boston, MA USA. Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. RP Schellenberg, GD (reprint author), Vet Affairs Med Ctr, 182B,1660 S Columbian Rd, Seattle, WA 98108 USA. FU NCRR NIH HHS [M01-RR00064]; NICHD NIH HHS [P01HD34565, P01 HD35476]; NIMH NIH HHS [MH57881] NR 45 TC 21 Z9 22 U1 6 U2 6 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 AUG 8 PY 2002 VL 114 IS 6 BP 667 EP 672 DI 10.1002/ajmg.10603 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 579NU UT WOS:000177185400015 PM 12210285 ER PT J AU Kato, Y Habas, R Katsuyama, Y Naar, AM He, X AF Kato, Y Habas, R Katsuyama, Y Naar, AM He, X TI A component of the ARC/mediator complex required for TGF beta/Nodal signalling SO NATURE LA English DT Article ID TRANSCRIPTIONAL REGULATION; DROSOPHILA HOMOLOGS; MEDIATOR COMPLEX; COFACTOR COMPLEX; BETA SIGNALS; COACTIVATOR; PROTEIN; INDUCTION; SMADS; GENE AB The transforming growth factor beta (TGFbeta) family of cytokines, including Nodal, Activin and bone morphogenetic protein (BMP), have essential roles in development and tumorigenesis(1,2). TGFbeta molecules activate the Smad family of signal transducers, which form complexes with specific DNA-binding proteins to regulate gene expression(1,2). Two discrete Smad-dependent signalling pathways have been identified: TGFbeta, Activin and Nodal signal via the Smad2 (or Smad3)-Smad4 complex, whereas BMP signals via the Smad1-Smad4 complex(1,2). How distinct Smad complexes regulate specific gene expression is not fully understood. Here we show that ARC105, a component of the activator-recruited co-factor (ARC)(3) complex or the metazoan Mediator complex, is essential for TGFbeta/Activin/Nodal/Smad2/3 signal transduction. Expression of ARC105 stimulates Activin/Nodal/Smad2 signalling in Xenopus laevis embryos, inducing axis duplication and mesendoderm differentiation, and enhances TGFbeta response in human cells. Depletion of ARC105 inhibits TGFbeta/Activin/Nodal/Smad2/3 signalling and Xenopus axis formation, but not BMP/Smad1 signalling. ARC105 protein binds to Smad2/3-Smad4 in response to TGFbeta and is recruited to Activin/Nodal-responsive promoters in chromatin in a Smad2-dependent fashion. Thus ARC105 is a specific and key ARC/Mediator component linking TGFbeta/Activin/Nodal/Smad2/3 signalling to transcriptional activation. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Neurol,Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Cell Biol, Charlestown, MA 02129 USA. RP He, X (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Neurol,Div Neurosci, Boston, MA 02115 USA. NR 30 TC 111 Z9 119 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 8 PY 2002 VL 418 IS 6898 BP 641 EP 646 DI 10.1038/nature00969 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 581RA UT WOS:000177305600043 PM 12167862 ER PT J AU Herbrecht, R Denning, DW Patterson, TF Bennett, JE Greene, RE Oestmann, JW Kern, WV Marr, KA Ribaud, P Lortholary, O Sylvester, R Rubin, RH Wingard, JR Stark, P Durand, C Caillot, D Thiel, E Chandrasekar, PH Hodges, MR Schlamm, HT Troke, PF de Pauw, B AF Herbrecht, R Denning, DW Patterson, TF Bennett, JE Greene, RE Oestmann, JW Kern, WV Marr, KA Ribaud, P Lortholary, O Sylvester, R Rubin, RH Wingard, JR Stark, P Durand, C Caillot, D Thiel, E Chandrasekar, PH Hodges, MR Schlamm, HT Troke, PF de Pauw, B CA Invasive Fungal Infect Grp Europea TI Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TRIAL AB Background Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. Methods In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. Results A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). Conclusions In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B. C1 Hop Hautepierre, Dept Hematol & Oncol, F-67098 Strasbourg, France. Univ Manchester, Manchester, Lancs, England. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NIAID, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Campus Virchow Klinikum, Charite, Berlin, Germany. Univ Freiberg, Med Klin, Freiburg, Germany. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Inst Pasteur, Paris, France. European Org Res Treatment Canc, Brussels, Belgium. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Florida, Coll Med, Gainesville, FL USA. Univ Calif San Diego, San Diego, CA 92103 USA. Hop Bocage, Dijon, France. Univ Hosp Benjamin Franklin, Berlin, Germany. Wayne State Univ, Sch Med, Detroit, MI USA. Pfizer, Global Res & Dev, New York, NY USA. Pfizer, Global Res & Dev, Sandwich, Kent, England. Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. Hop St Louis, Paris, France. RP Herbrecht, R (reprint author), Hop Hautepierre, Dept Hematol & Oncol, Ave Moliere, F-67098 Strasbourg, France. RI Herbrecht, Raoul/D-3471-2013; OI Herbrecht, Raoul/0000-0002-9381-4876; Denning, David/0000-0001-5626-2251 NR 13 TC 1775 Z9 1901 U1 7 U2 43 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 AUG 8 PY 2002 VL 347 IS 6 BP 408 EP 415 DI 10.1056/NEJMoa020191 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 587YR UT WOS:000177672400005 PM 12167683 ER PT J AU Podolsky, DK AF Podolsky, DK TI Inflammatory bowel disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ACTIVE CROHNS-DISEASE; PLACEBO-CONTROLLED TRIAL; DISTAL ULCERATIVE-COLITIS; RECOMBINANT HUMAN INTERLEUKIN-10; MONOCLONAL-ANTIBODY CA2; NECROSIS-FACTOR-ALPHA; GENOME-WIDE SEARCH; DOUBLE-BLIND; LONG-TERM; MAINTENANCE TREATMENT C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [P30 DK43351] NR 95 TC 2261 Z9 2362 U1 29 U2 234 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 AUG 8 PY 2002 VL 347 IS 6 BP 417 EP 429 DI 10.1056/NEJMra020831 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 587YR UT WOS:000177672400007 PM 12167685 ER PT J AU Hirsch, MS AF Hirsch, MS TI HIV drug resistance - A chink in the armor SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID THERAPY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 12 TC 7 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 AUG 8 PY 2002 VL 347 IS 6 BP 438 EP 439 DI 10.1056/NEJMe020072 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 587YR UT WOS:000177672400009 PM 12167687 ER PT J AU Fiore, E Fusco, C Romero, P Stamenkovic, I AF Fiore, E Fusco, C Romero, P Stamenkovic, I TI Matrix metalloproteinase 9 (MMP-9/gelatinase B) proteolytically cleaves ICAM-1 and participates in tumor cell resistance to natural killer cell-mediated cytotoxicity SO ONCOGENE LA English DT Article DE ICAM-1; MMP-9; tumor; proteases; cytotoxicity ID INTERCELLULAR-ADHESION MOLECULE-1; EPIDERMAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; RAT EMBRYO CELLS; L-SELECTIN CD62L; SERUM LEVELS; METASTATIC PHENOTYPE; ENDOTHELIAL-CELLS; TISSUE INHIBITOR; IV COLLAGENASE AB Shedding of intercellular adhesion molecule 1 (ICAM-1) is believed to play a role in tumor cell resistance to cell-mediated cytotoxicity. However, the mechanism whereby ICAM-1 is shed from the surface of tumor cells remains unclear. In this study, we have addressed the possibility that matrix metalloproteinases are implicated in ICAM-1 shedding. Our observations suggest a functional relationship between ICAM-1 and matrix metalloproteinase 9 (MMP-9) whereby ICAM-1 provides a cell surface docking mechanism for proMMP-9, which, upon activation, proteolytically cleaves the extracellular domain of ICAM-1 leading to its release from the cell surface. MMP-9-dependent shedding of ICAM-1 is found to augment tumor cell resistance to natural killer (NK) cell-mediated cytotoxicity. Taken together, our observations propose a mechanism for ICAM-1 shedding from the cell surface and provide support for MMP involvement in tumor cell evasion of immune surveillance. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02129 USA. Inst Univ Pathol, CH-1011 Lausanne, Switzerland. Ludwig Inst Canc Res, Lausanne Branch, CH-1066 Epalinges, Switzerland. RP Stamenkovic, I (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. FU NCI NIH HHS [CA55735]; NIGMS NIH HHS [GM48614] NR 49 TC 139 Z9 145 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 AUG 8 PY 2002 VL 21 IS 34 BP 5213 EP 5223 DI 10.1038/sj.onc.1205684 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 579TL UT WOS:000177193900003 PM 12149643 ER PT J AU McCollum, AD Catalano, PJ Haller, DG Mayer, RJ Macdonald, JS Benson, AB Fuchs, CS AF McCollum, AD Catalano, PJ Haller, DG Mayer, RJ Macdonald, JS Benson, AB Fuchs, CS TI Outcomes and toxicity in African-American and Caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COLORECTAL-CANCER; UNITED-STATES; SURVIVAL; RACE; BLACK AB Background: Previous studies have demonstrated that African-Americans with colon cancer have worse overall and stage-specific survival rates than Caucasians. Such differences could reflect variation in access to health care, in tumor biology, or in treatment efficacy. Little is known about potential differences in chemotherapy-related toxicities between African-Americans and Caucasians. In this study, we examined survival and toxic effects among African-American and Caucasian patients enrolled in a large, randomized phase III trial of adjuvant chemotherapy for resected colon cancer. Methods: We analyzed data on 3380 patients (344 African-Americans and 3036 Caucasians) enrolled in a randomized trial of adjuvant 5-fluorouracil-based chemotherapy in patients with stage II (high risk) and stage III colon cancer to evaluate differences in outcomes and toxicity. We compared disease-free survival (DFS) and overall survival (OS) between African-Americans and Caucasians by the Kaplan-Meier method, computed Cox proportional hazards by multivariable analysis, and compared treatment-related toxicity rates by Fisher's exact test. All statistical tests were two-sided. Results: We found no differences in DFS or OS between African-American and Caucasian patients. Five-year DFS was 57% (95% confidence interval [CI] = 52% to 62%) for African-Americans and 58% (95% CI = 56% to 60%) for Caucasians (P = .15), and 5-year OS was 65% (95% CI 60% to 70%) for African-Americans and 66% (95% Cl 64% to 68%) for Caucasians (P = .38). On multivariable analysis, no statistically significant difference in disease recurrence or death was detected between the racial/ethnic groups (hazard ratios for African-Americans versus Caucasians: disease recurrence = 1.1, 95% CI = 0.9 to 1.3; death = 1.1, 95% CI = 0.9 to 1.3). Treatment-related toxicity differed between the African-American and Caucasian patients, with African-Americans experiencing statistically significantly lower rates of diarrhea (P < .001), nausea (P < .001), vomiting (P = .01), stomatitis (P < .001), and overall toxicity (P = .005). Conclusions: In this study of patients with similar access to health care resources and treatment with adjuvant chemotherapy, we found similar 5-year DFS and OS in African-Americans and Caucasians with stage II and III colon cancer. The two groups derived similar benefits from adjuvant chemotherapy. Moreover, African-Americans appeared to experience less treatment-related toxicity. [J Natl Cancer Inst 2002;94:1160-7]. C1 Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Ctr Stat, Boston, MA 02115 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. St Vincent Clin Canc Ctr, New York, NY USA. Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA. RP McCollum, AD (reprint author), Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Ctr Stat, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA23318, CA32291, CA58415, CA15488, CA21115] NR 27 TC 87 Z9 89 U1 0 U2 0 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 AUG 7 PY 2002 VL 94 IS 15 BP 1160 EP 1167 PG 8 WC Oncology SC Oncology GA 580JH UT WOS:000177231100013 PM 12165641 ER PT J AU Bamshad, MJ Mummidi, S Gonzalez, E Ahuja, SS Dunn, DM Watkins, WS Wooding, S Stone, AC Jorde, LB Weiss, RB Ahuja, SK AF Bamshad, MJ Mummidi, S Gonzalez, E Ahuja, SS Dunn, DM Watkins, WS Wooding, S Stone, AC Jorde, LB Weiss, RB Ahuja, SK TI A strong signature of balancing selection in the 5 ' cis-regulatory region of CCR5 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-SEQUENCE VARIATION; MODERN HUMANS; HIV-1 INFECTION; STATISTICAL TESTS; POPULATION-GROWTH; GENETIC-VARIATION; EVOLUTION; POLYMORPHISMS; HAPLOTYPE; DIVERSITY AB CCR5 encodes a cell surface chemokine receptor molecule that serves as the principal coreceptor, with CD4, for HIV-type 1 (HIV-1). Varied HIV-1 susceptibility and time to progression to AIDS have been associated with polymorphisms in CCR5. Many of these polymorphisms are located in the 5' cis-regulatory region of CCR5, suggesting that it may have been a target of natural selection. We characterized CCR5 sequence variation in this region in 400 chromosomes from worldwide populations and compared it to a genome-wide analysis of 100 AN polymorphisms typed in the same populations. Variation was substantially higher than expected and characterized by an excess of intermediate-frequency alleles. A genealogy of CCR5 haplotypes had deep branch lengths despite markedly little differentiation among populations. This finding suggested a deviation from neutrality not accounted for by population structure, which was confirmed by tests for natural selection. These results are strong evidence that balancing selection has shaped the pattern of variation in CCR5 and suggest that HIV-1 resistance afforded by CCR5 5' cis-regulatory region haplotypes may be the consequence of adaptive changes to older pathogens. C1 Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Res Ctr AIDS & HIV 1 Infect, Vet Adm, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. Univ New Mexico, Dept Anthropol, Albuquerque, NM 87131 USA. RP Bamshad, MJ (reprint author), Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. RI Mummidi, Srinivas/C-1004-2008; Stone, Anne/B-5719-2009 OI Mummidi, Srinivas/0000-0002-4068-6380; FU NCRR NIH HHS [M01 RR000064, RR-00064]; NIAID NIH HHS [R21 AI046326, R01 AI043279, R01 AI046326, AI43279, AI46326, R37 AI046326]; NIGMS NIH HHS [GM-59290, R01 GM059290] NR 49 TC 136 Z9 139 U1 0 U2 14 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 AUG 6 PY 2002 VL 99 IS 16 BP 10539 EP 10544 DI 10.1073/pnas.162046399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 582HC UT WOS:000177343200059 PM 12149450 ER PT J AU Yechoor, VK Patti, ME Saccone, R Kahn, CR AF Yechoor, VK Patti, ME Saccone, R Kahn, CR TI Coordinated patterns of gene expression for substrate and energy metabolism in skeletal muscle of diabetic mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE-C; ACTIVATED RECEPTOR-ALPHA; ACID BETA-OXIDATION; INSULIN-RESISTANCE; HEXOKINASE-II; GLUCOSE TRANSPORTERS; TARGETED DISRUPTION; MESSENGER-RNAS; GLUT4; RATS AB Metabolic abnormalities underlying diabetes are primarily the result of the lack of adequate insulin action and the associated changes in protein phosphorylation and gene expression. To define the full set of alterations in gene expression in skeletal muscle caused by diabetes and the loss of insulin action, we have used Affymetrix oligonucleotide microarrays and streptozotocin-diabetic mice. Of the genes studied, 235 were identified as changed in diabetes, with 129 genes up-regulated and 106 down-regulated. Analysis revealed a coordinated regulation at key steps in glucose and lipid metabolism, mitochondrial electron transport, transcriptional regulation, and protein trafficking. mRNAs for all of the enzymes of the fatty acid beta-oxidation pathway were increased, whereas those for GLUT4, hexokinase II, the E1 component of the pyruvate dehydrogenase complex, and subunits of all four complexes of the mitochondrial electron transport chain were all coordinately down-regulated. Only about half of the alterations in gene expression in diabetic mice could be corrected toward normal after 3 days of insulin treatment and euglycemia. These data point to as of yet undefined mechanisms for highly coordinated regulation of gene expression by insulin and potential new targets for therapy of diabetes mellitus. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK033201, DK33201, DK36836-15, DK45935, P30 DK036836, R01 DK045935] NR 41 TC 111 Z9 113 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 6 PY 2002 VL 99 IS 16 BP 10587 EP 10592 DI 10.1073/pnas.142301999 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 582HC UT WOS:000177343200068 PM 12149437 ER PT J AU Prota, AE Sage, DR Stehle, T Fingeroth, JD AF Prota, AE Sage, DR Stehle, T Fingeroth, JD TI The crystal structure of human CD21: Implications for Epstein-Barr virus and C3d binding SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COMPLEMENT RECEPTOR TYPE-2; HUMAN LYMPHOCYTES-B; LIGAND-BINDING; CR-2; IDENTIFICATION; PROTEIN; INFECTION; PAIR; DYNAMICS; CR2/CD21 AB Human complement receptor type 2 (CD21) is the cellular receptor for Epstein-Barr virus (EBV), a human tumor virus. The N-terminal two short consensus repeats (SCR1-SCR2) of the receptor interact with the EBV glycoprotein gp350/220 and also with the natural CD21 ligand C3d. Here we present the crystal structure of the CD21 SCR1-SCR2 fragment in the absence of ligand and demonstrate that it is able to bind EBV. Based on a functional analysis of wild-type and mutant CD21 and molecular modeling, we identify a likely region for EBV attachment and demonstrate that this region is not involved in the interaction with C3d. A comparison with the previously determined structure of CD21 SCR1-SCR2 in complex with C3d shows that, in both cases, CD21 assumes compact V-shaped conformations. However, our analysis reveals a surprising degree of flexibility at the SCR1-SCR2 interface, suggesting interactions between the two domains are not specific. We present evidence that the V-shaped conformation is induced by deglycosylation of the protein, and that physiologic glycosylation of CD21 would result in a more extended conformation, perhaps with additional epitopes for C3d binding. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Harvard Inst Med, Div Expt Med & Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. RP Stehle, T (reprint author), Harvard Univ, Sch Med, 4 Blackfan Circle, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI045716, AI45716]; NIDCR NIH HHS [DE12186] NR 48 TC 60 Z9 66 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 6 PY 2002 VL 99 IS 16 BP 10641 EP 10646 DI 10.1073/pnas.162360499 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 582HC UT WOS:000177343200077 PM 12122212 ER PT J AU Roumiantsev, S Shah, NP Gorre, ME Nicoll, J Brasher, BB Sawyers, CL Van Etten, RA AF Roumiantsev, S Shah, NP Gorre, ME Nicoll, J Brasher, BB Sawyers, CL Van Etten, RA TI Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE KINASE; IN-VIVO; BCR; SRC; CELLS; BINDING; PROTEIN; THERAPY; GROWTH; VITRO AB The Abl tyrosine kinase inhibitor STI-571 is effective therapy for stable phase chronic myeloid leukemia (CIVIL) patients, but the majority of CML blast-crisis patients that respond to STI-571 relapse because of reactivation of Bcr-Abl signaling. Mutations of Thr-315 in the Abl kinase domain to lie (T315I) were previously described in STI-571-resistant patients and likely cause resistance from steric interference with drug binding. Here we identify mutations of Tyr-253 in the nucleoticle-binding (P) loop of the Abl kinase domain to Phe or His in patients with advanced CML and acquired STI-571 resistance. Bcr-Abl Y253F demonstrated intermediate resistance to STI-571 in vitro and in vivo when compared with Bcr-Abl T315I. The response of Abl proteins to STI-571 was influenced by the regulatory state of the kinase and by tyrosine phosphorylation. The sensitivity of purified c-Abl to STI-571 was increased by a dysregulating mutation (P112L) in the Src homology 3 domain of Abl but decreased by phosphorylation at the regulatory Tyr-393. In contrast, the Y253F mutation dysregulated c-Abl and conferred intrinsic but not absolute resistance to STI-571 that was independent of Tyr-393 phosphorylation. The Abl P-loop is a second target for mutations that confer resistance to STI-571 in advanced CIVIL, and the Y253F mutation may impair the induced-fit interaction of STI-571 with the Abl catalytic domain rather than sterically blocking binding of the drug. Because clinical resistance induced by the Y253F mutation might be overcome by dose escalation of STI-571, molecular genotyping of STI-571-resistant patients may provide information useful for rational therapeutic management. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Sawyers, Charles/G-5327-2016 FU NCI NIH HHS [CA72465]; NIGMS NIH HHS [GM07185, T32 GM007185] NR 26 TC 190 Z9 193 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 6 PY 2002 VL 99 IS 16 BP 10700 EP 10705 DI 10.1073/pnas.162140299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 582HC UT WOS:000177343200087 PM 12149456 ER PT J AU Chan, C Berthiaume, F Washizu, J Toner, M Yarmush, ML AF Chan, C Berthiaume, F Washizu, J Toner, M Yarmush, ML TI Metabolic pre-conditioning of cultured cells in physiological levels of insulin: Generating resistance to the lipid-accumulating effects of plasma in hepatocytes (vol 78, pg 753, 2002) SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Correction C1 Harvard Univ, Sch Med, Ctr Engn Med Surg Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Chan, C (reprint author), Harvard Univ, Sch Med, Ctr Engn Med Surg Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD AUG 5 PY 2002 VL 79 IS 3 BP 364 EP 364 DI 10.1002/bit.10420 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 574GW UT WOS:000176881400016 ER PT J AU Canuso, CM Goldstein, JM Wojcik, J Dawson, R Brandman, D Klibanski, A Schildkraut, JJ Green, AI AF Canuso, CM Goldstein, JM Wojcik, J Dawson, R Brandman, D Klibanski, A Schildkraut, JJ Green, AI TI Antipsychotic medication, prolactin elevation, and ovarian function in women with schizophrenia and schizoaffective disorder SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; schizoaffective disorder; antipsychotic medication; psychosis; prolactin; women; ovarian function ID INDUCED HYPERPROLACTINEMIA; OLANZAPINE; PREVALENCE; CLOZAPINE; ETIOLOGY; SYMPTOMS; ESTROGEN; TRIAL AB Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinemia is thought to account for high rates of menstrual dysfunction and diminished estrogen levels in women with schizophrenia. However, few studies have directly assessed the relationships between prolactin, menstrual function, and ovarian hormone levels in this population. Sixteen premenopausal women with schizophrenia and schizoaffective disorder, eight treated with an antipsychotic with prolactin-elevating potential (five with typical antipsychotics and three with risperidone) and eight treated with an antipsychotic with prolactin-sparing potential (seven with olanzapine and one with clozapine), were studied for eight weeks. Data were collected on menstrual functioning and on serum prolactin, estradiol, and progesterone levels, and were compared between subjects who received an antipsychotic with prolactin-elevating potential and an antipsychotic with prolactin-sparing potential, and between subjects with hyperprolactinemia (N=6) and normoprolactinemia (N=10). Additionally, peak ovarian hormone levels were compared to normal values. While mean prolactin levels of subjects who received an antipsychotic with prolactin-elevating potential were significantly greater than those of subjects who received an antipsychotic with prolactin-sparing potential, there were no differences in rates of menstrual dysfunction or in ovarian hormone values between the two groups. Additionally, similar rates of menstrual dysfunction and ovarian hormone values were observed between the hyperprolactinemic and normoprolactinemic subjects. Moreover, irrespective of medication type or prolactin status, most subjects had peak estradiol levels below normal reference values for the periovulatory phase of the menstrual cycle. While our sample size is small, warranting the need for further investigation, the findings of this preliminary Study suggest that antipsychotic-induced hyperprolactinemia, alone, may not adequately explain the observed ovarian dysfunction in women with schizophrenia. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Frontier Sci Technol, Boston, MA 02115 USA. RP Canuso, CM (reprint author), Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. FU NIMH NIH HHS [MH49891, MH56956] NR 42 TC 56 Z9 58 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 5 PY 2002 VL 111 IS 1 BP 11 EP 20 AR PII S0165-1781(02)00123-3 DI 10.1016/S0165-1781(02)00123-3 PG 10 WC Psychiatry SC Psychiatry GA 585EK UT WOS:000177511200002 PM 12140115 ER PT J AU Wehner, KA Ayala, L Kim, Y Young, PJ Hosler, BA Lorson, CL Baserga, SJ Francis, JW AF Wehner, KA Ayala, L Kim, Y Young, PJ Hosler, BA Lorson, CL Baserga, SJ Francis, JW TI Survival motor neuron protein in the nucleolus of mammalian neurons SO BRAIN RESEARCH LA English DT Article DE survival motor neuron protein; spinal muscular atrophy; nucleolus; fibrillarin; Cajal body; U3 snoRNA ID SPINAL MUSCULAR-ATROPHY; DISEASE GENE-PRODUCT; TRACT-BINDING PROTEIN; NUCLEAR COILED BODY; SMN PROTEIN; PERINUCLEOLAR COMPARTMENT; SNRNP BIOGENESIS; FETAL TISSUES; RIBOSOMAL-RNA; HNRNP-I AB Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by mutations in the survival motor neuron gene (SMN1). While it has been shown that the SMN protein is involved in spliceosome biogenesis and pre-mRNA splicing, there is increasing evidence indicating that SMN may also perform important functions in the nucleolus. We demonstrate here through the use of a previously characterized polyclonal anti-SMN antibody, abSMN, that the SMN protein shows a striking colocalization with the nucleolar protein, fibrillarin, in both nucleoli and Cajal bodies/gems of primary neurons. Immunoblot analysis with antifibrillarin and two different anti-SMN antibodies reveals that SMN and fibrillarin also cofractionate in the insoluble protein fraction of cultured cell lysates. Immunoprecipitation experiments using whole cell extracts of HeLa cells and cultured neurons revealed that abSMN coprecipitated small amounts of the U3 small nucleolar RNA (snoRNA) previously shown to be associated with fibrillarin in vivo. These studies raise the possibility that SMN may serve a function in rRNA maturation/ribosome synthesis similar to its role in spliceosome biogenesis. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Dept Neurol, Charlestown, MA 02129 USA. Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Arizona State Univ, Dept Biol, Tempe, AZ 85287 USA. RP Francis, JW (reprint author), Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Dept Neurol, Bldg 114,16th St,Room 3003, Charlestown, MA 02129 USA. FU NIGMS NIH HHS [GM52581]; NINDS NIH HHS [R01 NS41584-01, R01 NS37912, NS38679-01] NR 60 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 2 PY 2002 VL 945 IS 2 BP 160 EP 173 AR PII S0006-8993(02)02750-6 DI 10.1016/S0006-8993(02)02750-6 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 586LU UT WOS:000177586100002 PM 12126878 ER PT J AU Tung, CH Lin, YH Moon, WK Weissleder, R AF Tung, CH Lin, YH Moon, WK Weissleder, R TI A receptor-targeted near-infrared fluorescence probe for in vivo tumor imaging SO CHEMBIOCHEM LA English DT Article DE fluorescence; folic acid; imaging agents; near infrared; receptors ID CONTRAST AGENTS; MRI C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St,Room 5406, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50 CA 86355, R33 CA 88365] NR 19 TC 84 Z9 86 U1 0 U2 28 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD AUG 2 PY 2002 VL 3 IS 8 BP 784 EP 786 DI 10.1002/1439-7633(20020802)3:8<784::AID-CBIC784>3.0.CO;2-X PG 3 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 582PD UT WOS:000177359600012 PM 12203978 ER PT J AU Gilmore, AP Valentijn, AJ Wang, PB Ranger, AM Bundred, N O'Hare, MJ Wakeling, A Korsmeyer, SJ Streuli, CH AF Gilmore, AP Valentijn, AJ Wang, PB Ranger, AM Bundred, N O'Hare, MJ Wakeling, A Korsmeyer, SJ Streuli, CH TI Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; PROTEIN-KINASE AKT; TYROSINE KINASE; BREAST-CANCER; EGF RECEPTOR; BH3 DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; MONOCLONAL-ANTIBODY; MAMMARY EPITHELIUM; ANTICANCER THERAPY AB Novel cancer chemotherapeutics are required to induce apoptosis by activating pro-apoptotic proteins. Both epidermal growth factor (EGF) and insulin-like growth factor (IGF) provide potent survival stimuli in many epithelia, and activation of their receptors is commonly observed in solid human tumors. Here we demonstrate that blockade of the EGF receptor by a new drug in phase III clinical trails for cancer, ZD1839, potently induces apoptosis in mammary epithelial cell lines and primary cultures, as well as in a primary pleural effusion from a breast cancer patient. We identified the mechanism of apoptosis induction by ZD1839. We showed that it prevents cell survival by activating the pro-apoptotic protein BAD. Moreover, we demonstrate that IGF transactivates the EGF receptor and that ZD1839 blocks IGF-mediated phosphorylation of MAPK and BAD. Many cancer therapies kill tumor cells by inducing apoptosis as a consequence of targeting DNA; however, the threshold at which apoptosis can be triggered through DNA damage is often different from that in normal cells. Our results indicate that by targeting a growth factor-mediated survival signaling pathway, BAD phosphorylation can be manipulated therapeutically to induce apoptosis. C1 Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England. Univ S Manchester Hosp, Dept Surg, Manchester M20 8LR, Lancs, England. UCL, Ludwig Inst Canc Res, Breast Canc Lab, Dept Surg, London W1P 7LD, England. AstraZeneca, Macclesfield SK10 4TG, Cheshire, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Gilmore, AP (reprint author), Univ Manchester, Sch Biol Sci, Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. EM agilmore@man.ac.uk NR 76 TC 167 Z9 180 U1 0 U2 4 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 AUG 2 PY 2002 VL 277 IS 31 BP 27643 EP 27650 DI 10.1074/jbc.M108863200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579QR UT WOS:000177189800011 PM 12011069 ER PT J AU Koipally, J Georgopoulos, K AF Koipally, J Georgopoulos, K TI A molecular dissection of the repression circuitry of Ikaros SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE DEACETYLASE COMPLEXES; CHROMATIN REMODELING COMPLEXES; TRANSCRIPTION FACTOR; LYMPHOCYTE DEVELOPMENT; GENE; PROTEIN; FAMILY; AIOLOS; MUTATION; PARTNER AB Ikaros is a key regulator of the hemo-lymphoid system in which it is presumed to function by both potentiating and repressing gene expression. Repression is mediated through two independent domains at the N and C terminus of the protein, both of which can independently recruit the corepressors Mi-2beta, Sin3A, and Sin3B and the Class I histone deacetylases 1 and 2; the N-terminal domain can also associate with the corepressor CtBP. Here we describe a detailed dissection of these two domains and identify the minimal repression modules and the corepressor requirements for their activity. Based on these studies, we describe mutations in a full-length Ikaros protein that abrogate interactions with each of the identified corepressors and abolish the protein's function as a repressor. Finally, we show that, barring CtBP, the Ikaros family members Aiolos, Helios, and Eos can associate with all of the identified corepressors of Ikaros including its newly identified interactors, Class II HDACs. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), MGH E, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01-AI380342-08] NR 29 TC 36 Z9 39 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 2 PY 2002 VL 277 IS 31 BP 27697 EP 27705 DI 10.1074/jbc.M201694200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579QR UT WOS:000177189800017 PM 12015313 ER PT J AU Lof, GL AF Lof, GL TI Two comments on this assessment series SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Editorial Material ID PHONOLOGICAL DISORDERS C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Commun Sci & Disorders, Boston, MA 02129 USA. RP Lof, GL (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Commun Sci & Disorders, Charlestown Navy Yard,36 1st Ave, Boston, MA 02129 USA. EM glof@mghihp.edu NR 21 TC 5 Z9 5 U1 1 U2 1 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 EI 1558-9110 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD AUG PY 2002 VL 11 IS 3 BP 255 EP 256 DI 10.1044/1058-0360(2002/028) PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 714HC UT WOS:000184906400010 ER PT J AU Taylor, AE Stubbs, C Singer, DE Curhan, G Crowley, WF AF Taylor, AE Stubbs, C Singer, DE Curhan, G Crowley, WF TI An instrument for determining the amount of NIH support for clinical investigations at one academic health center SO ACADEMIC MEDICINE LA English DT Article AB Purpose. Although interest in supporting clinical investigators is increasing, information regarding the quantity, spectrum, and specific types of clinical research performed in academic health centers (AHCs) is generally not available. The authors report on an instrument to quantify the National Institutes of Health (NIH)-funded component of clinical research at one institution. Method. A systematic review of all NIH grants awarded to Massachusetts General Hospital (MGH) in fiscal year (FY) 1997-98 was performed using public information from two NIH Internet sources. Research abstracts from all 487 grants were reviewed and the percentage and type of clinical research activity within each was estimated and compared with estimates provided by a subset of principal investigators. Results. During FY 1997-98, the NIGH received $134 million in total NIH funding; $39.9 million (30%) supported the broadest definition of clinical research (that using human materials). When the definition of clinical research was narrowed to direct interaction between investigator and patient for investigative purposes (patient-oriented research), the total for clinical research was $18.2 million. These numbers significantly exceeded the institution's previous estimates of $.6 million for NIH-sponsored clinical trials and $2.2 million for population-based studies. Conclusions. Clinical investigation is an important component of AHCs' research portfolios from several perspectives, not the least of which is financial. Data on the clinical component of an institution's research effort should be collected prospectively and nationally to inform the optimal allocation of research resources and the alignment of the AHC's infrastructure. C1 Massachusetts Gen Hosp, Clin Res Program, Clin Res Support Off, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Clin Res Program, Adm & Finance, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Res Program, Educ Unit, Boston, MA 02114 USA. RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Clin Res Program, Clin Res Support Off, Lawrence House 2,55 Fruit St, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD AUG PY 2002 VL 77 IS 8 BP 824 EP 830 DI 10.1097/00001888-200208000-00015 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 617MJ UT WOS:000179365200011 PM 12176698 ER PT J AU Bouma, BE Tearney, GJ AF Bouma, BE Tearney, GJ TI Clinical imaging with optical coherence tomography SO ACADEMIC RADIOLOGY LA English DT Review ID ACUTE CORONARY SYNDROMES; INTRAVASCULAR ULTRASOUND; IN-VIVO; HILAR CHOLANGIOCARCINOMA; BARRETTS-ESOPHAGUS; ARTERY DISEASE; LASER SOURCE; BIOPSY; TISSUE; ADENOCARCINOMA C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 64 TC 40 Z9 43 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 2002 VL 9 IS 8 BP 942 EP 953 DI 10.1016/S1076-6332(03)80465-8 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 582JV UT WOS:000177347900011 PM 12186444 ER PT J AU Bremer, C Tung, CH Weissleder, R AF Bremer, C Tung, CH Weissleder, R TI Molecular imaging of MMP expression and therapeutic MMP inhibition SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Conference CY OCT 14-18, 2001 CL CAPRI, ITALY SP Bracco Imaging, Bracco Res, DuPont Pharmaceut, Nycomed Amersham Imaging, Schering, Guerbet, Berlex, Bracco Byk Gulden, Bracco Res, Switzerland, Daiichi Pharmaceut, Epix Med, Mallinckrodt, MetalProbe, Nihon Medi Phys, Nihon Schering ID VIVO C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Bremer, C (reprint author), Univ Munster, Dept Clin Radiol, Albert Schweitzer Str 33, D-48129 Munster, Germany. FU NCI NIH HHS [CA088365] NR 3 TC 31 Z9 32 U1 0 U2 5 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 AUG PY 2002 VL 9 SU 2 BP S314 EP S315 DI 10.1016/S1076-6332(03)80214-3 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 583QZ UT WOS:000177420700014 PM 12188259 ER PT J AU Harisinghani, MG Barentsz, JO Hahn, PF Deserno, W de la Rosette, J Saini, S Marten, K Weissleder, R AF Harisinghani, MG Barentsz, JO Hahn, PF Deserno, W de la Rosette, J Saini, S Marten, K Weissleder, R TI MR lymphangiography for detection of minimal nodal disease in patients with prostate cancer SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Conference CY OCT 14-18, 2001 CL CAPRI, ITALY SP Bracco Imaging, Bracco Res, DuPont Pharmaceut, Nycomed Amersham Imaging, Schering, Guerbet, Berlex, Bracco Byk Gulden, Bracco Res, Switzerland, Daiichi Pharmaceut, Epix Med, Mallinckrodt, MetalProbe, Nihon Medi Phys, Nihon Schering ID SUPERPARAMAGNETIC IRON-OXIDE; ASSESSING LYMPH-NODES; CONTRAST AGENT; METASTASES; LYMPHOGRAPHY; HEAD; NECK C1 Massachusetts Gen Hosp, Dept Abdominal Imaging, Boston, MA 02114 USA. Univ Nijmegen Hosp, NL-6500 HB Nijmegen, Netherlands. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging, White 270, Boston, MA 02114 USA. RI Barentsz, Jelle/D-3515-2009 NR 14 TC 22 Z9 23 U1 0 U2 1 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 AUG PY 2002 VL 9 SU 2 BP S312 EP S313 DI 10.1016/S1076-6332(03)80213-1 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 583QZ UT WOS:000177420700013 PM 12188258 ER PT J AU Ntziachristos, V Bremer, C Tung, C Weissleder, R AF Ntziachristos, V Bremer, C Tung, C Weissleder, R TI Imaging cathepsin B up-regulation in HT-1080 tumor models using fluorescence-mediated molecular tomography (FMT) SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Conference CY OCT 14-18, 2001 CL CAPRI, ITALY SP Bracco Imaging, Bracco Res, DuPont Pharmaceut, Nycomed Amersham Imaging, Schering, Guerbet, Berlex, Bracco Byk Gulden, Bracco Res, Switzerland, Daiichi Pharmaceut, Epix Med, Mallinckrodt, MetalProbe, Nihon Medi Phys, Nihon Schering ID PROBES C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Rm 5406, Charlestown, MA 02129 USA. FU NCI NIH HHS [P50 CA86355] NR 8 TC 22 Z9 22 U1 0 U2 1 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 AUG PY 2002 VL 9 SU 2 BP S323 EP S325 DI 10.1016/S1076-6332(03)80217-9 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 583QZ UT WOS:000177420700017 PM 12188262 ER PT J AU Sahani, DV Saini, S Kalra, MK Michael, M Hahn, PF AF Sahani, DV Saini, S Kalra, MK Michael, M Hahn, PF TI Liver lesion detection and characterization with sequential use of hepatobiliary contrast agent mangafodipir trisodium and gadolinium-DTPA in a single imaging protocol SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Conference CY OCT 14-18, 2001 CL CAPRI, ITALY SP Bracco Imaging, Bracco Res, DuPont Pharmaceut, Nycomed Amersham Imaging, Schering, Guerbet, Berlex, Bracco Byk Gulden, Bracco Res, Switzerland, Daiichi Pharmaceut, Epix Med, Mallinckrodt, MetalProbe, Nihon Medi Phys, Nihon Schering ID MN-DPDP; MR C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Ellison 234-E,55 Fruit St, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 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 AUG PY 2002 VL 9 SU 2 BP S460 EP S462 DI 10.1016/S1076-6332(03)80263-5 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 583QZ UT WOS:000177420700063 PM 12188308 ER PT J AU Saini, S Jhaveri, KS Sahani, DV Varghese, JC Hahn, PF AF Saini, S Jhaveri, KS Sahani, DV Varghese, JC Hahn, PF TI Evaluation of simethicone coated cellulose (SonoRx (TM)) as a negative oral contrast agent for abdominal-pelvic computed tomography SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Conference CY OCT 14-18, 2001 CL CAPRI, ITALY SP Bracco Imaging, Bracco Res, DuPont Pharmaceut, Nycomed Amersham Imaging, Schering, Guerbet, Berlex, Bracco Byk Gulden, Bracco Res, Switzerland, Daiichi Pharmaceut, Epix Med, Mallinckrodt, MetalProbe, Nihon Medi Phys, Nihon Schering ID HELICAL CT; ABDOMEN C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 7 TC 1 Z9 2 U1 1 U2 2 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 AUG PY 2002 VL 9 SU 2 BP S357 EP S358 DI 10.1016/S1076-6332(03)80229-5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 583QZ UT WOS:000177420700029 PM 12188274 ER PT J AU Schellenberger, EA Hogemann, D Josephson, L Weissleder, R AF Schellenberger, EA Hogemann, D Josephson, L Weissleder, R TI Annexin V-CLIO: A nanoparticle for detecting apoptosis by MRI SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Conference CY OCT 14-18, 2001 CL CAPRI, ITALY SP Bracco Imaging, Bracco Res, DuPont Pharmaceut, Nycomed Amersham Imaging, Schering, Guerbet, Berlex, Bracco Byk Gulden, Bracco Res, Switzerland, Daiichi Pharmaceut, Epix Med, Mallinckrodt, MetalProbe, Nihon Medi Phys, Nihon Schering C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Schellenberger, EA (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Rm 5419,Bldg 149,13th, Charlestown, MA 02129 USA. NR 0 TC 36 Z9 37 U1 1 U2 8 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 AUG PY 2002 VL 9 SU 2 BP S310 EP S311 DI 10.1016/S1076-6332(03)80212-X PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 583QZ UT WOS:000177420700012 PM 12188257 ER PT J AU Wunderbaldinger, P Josephson, L Weissleder, R AF Wunderbaldinger, P Josephson, L Weissleder, R TI Crosslinked iron oxides (CLIO): A new platform for the development of targeted MR contrast agents SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Conference CY OCT 14-18, 2001 CL CAPRI, ITALY SP Bracco Imaging, Bracco Res, DuPont Pharmaceut, Nycomed Amersham Imaging, Schering, Guerbet, Berlex, Bracco Byk Gulden, Bracco Res, Switzerland, Daiichi Pharmaceut, Epix Med, Mallinckrodt, MetalProbe, Nihon Medi Phys, Nihon Schering ID CELLS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Univ Vienna, Dept Radiol, A-1090 Vienna, Austria. RP Wunderbaldinger, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5403, Charlestown, MA 02129 USA. NR 7 TC 102 Z9 105 U1 1 U2 24 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 AUG PY 2002 VL 9 SU 2 BP S304 EP S306 DI 10.1016/S1076-6332(03)80210-6 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 583QZ UT WOS:000177420700010 PM 12188255 ER PT J AU Shibata, N Hirano, A Hedley-Whyte, ET Dal Canto, MC Nagai, R Uchida, K Horiuchi, S Kawaguchi, M Yamamoto, T Kobayashi, M AF Shibata, N Hirano, A Hedley-Whyte, ET Dal Canto, MC Nagai, R Uchida, K Horiuchi, S Kawaguchi, M Yamamoto, T Kobayashi, M TI Selective formation of certain advanced glycation end products in spinal cord astrocytes of humans and mice with superoxide dismutase-1 mutation SO ACTA NEUROPATHOLOGICA LA English DT Article DE advanced glycation end products; amyotrophic lateral sclerosis; astrocyte; superoxide dismutase; transgenic mice ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID-BETA-PEPTIDE; MEMBRANE LIPID-PEROXIDATION; PROTEIN-BOUND ACROLEIN; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; PARKINSON DISEASE; CORTICAL-NEURONS; GENE-EXPRESSION; 3-DEOXYGLUCOSONE AB Recent studies have documented carbonyl stress involvement in the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS). The aim of the present study was to assess a role for carbonyl stress in motor neuron degeneration associated with superoxide dismutase-1 (SOD1) mutant familial ALS and its transgenic mouse model, using an immunohistochemical investigation of advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs). In the spinal cords from six familial ALS patients with SOD1 A4V mutation and six transgenic mice expressing G93A mutant human SOD1, immunoreactivities for N-epsilon-(carboxyethyl)lysine, argpyrimidine, pyrraline and N-epsilon-(carboxymethyl)lysine as AGEs were distinct in almost all of the reactive astrocytes and obscure in the residual neurons, whereas no immunoreactivity for pentosidine as an AGE, or 4-hydroxy-2-nonenal-histidine, malondialdehyde-lysine or acrolein-lysine as ALEs was detectable. Spinal cords from age-matched control humans and mice exhibited no significant immunoreactivities for the examined products. Our results indicate that protein glycation, but not lipid peroxidation, is enhanced in ALS patients with an SOD1 mutation and mutant SOD1 transgenic mice, in which certain AGEs are selectively formed in the spinal cord astrocytes. C1 Tokyo Womens Med Univ, Dept Pathol, Shinjuku Ku, Tokyo 1628666, Japan. Montefiore Med Ctr, Div Neuropathol, Bronx, NY 10467 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA. Kumamoto Univ, Sch Med, Dept Biochem, Kumamoto 8600811, Japan. Nagoya Univ, Grad Sch Bioagr Sci, Lab Food & Biodynam, Chikusa Ku, Nagoya, Aichi 4648601, Japan. RP Shibata, N (reprint author), Tokyo Womens Med Univ, Dept Pathol, Shinjuku Ku, Kawada Cho 8-1, Tokyo 1628666, Japan. NR 52 TC 33 Z9 33 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD AUG PY 2002 VL 104 IS 2 BP 171 EP 178 DI 10.1007/s00401-002-0537-5 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 578UQ UT WOS:000177139300008 PM 12111360 ER PT J AU Anton, RF Lieber, C Tabakoff, B AF Anton, RF Lieber, C Tabakoff, B CA CDTect Study Grp TI Carbohydrate-deficient transferrin and gamma-glutamyltransferase for the detection and monitoring of alcohol use: Results from a multisite study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-JUL 01, 1999 CL SANTA BARBARA, CALIFORNIA SP Res Soc Alcoholism DE alcohol; markers; carbohydrate-deficient transferrin; gamma-glutamyltransferase; relapse ID ANION-EXCHANGE CHROMATOGRAPHY; GLUTAMYL-TRANSFERASE; LABORATORY MARKERS; OUTPATIENT ALCOHOLICS; BIOLOGICAL MARKERS; SERUM; CONSUMPTION; DRINKING; DEPENDENCE; ABUSE AB Background: The purpose of this article is to evaluate the biological marker of heavy alcohol use, carbohydrate-deficient transferrin (CDT), in contrast to the older and more widely used gamma-glutamyltransferase (GGT) for the detection and monitoring of heavy alcohol use. Methods: In this report, CDT and GGT sensitivity and specificity for heavy alcohol intake are examined in a large multisite study in which 444 recently admitted inpatient alcoholics were compared with 204 matched social drinker controls. In addition, changes in these biomarkers were evaluated during an initial abstinence period and biweekly over 14 weeks of monitoring to compare changes in CDT and GGT during continued abstinence or relapse. Results: CDT and GGT were comparable in identifying heavy alcohol consumption in men, but GGT appeared to be better for women, For both genders, when these markers were combined, there was better sensitivity than when used alone. CDT and GGT both decreased during 4 weeks of abstinence. When we used a 30% increase from baseline abstinent levels as an indicator, CDT appeared marginally better than GGT at indicating relapse in men but not in women. For men in particular, relapse over the course of the study was best identified by evaluating changes (30% increase) in both markers simultaneously. Conclusions: These results support the utility, of CDT, especially when used in conjunction with GGT. as an aid in detecting and monitoring heavy alcohol consumption. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Univ Colorado, Dept Pharmacol, Sch Med, Denver, CO 80202 USA. RP Anton, RF (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,POB 250861,POB 250861, Charleston, SC 29425 USA. NR 59 TC 100 Z9 102 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2002 VL 26 IS 8 BP 1215 EP 1222 DI 10.1097/01.ALC.0000023986.42254.F5 PG 8 WC Substance Abuse SC Substance Abuse GA 586BC UT WOS:000177561400012 PM 12198396 ER PT J AU Watanabe, CT Maynard, C Ritchie, JL AF Watanabe, CT Maynard, C Ritchie, JL TI Short-term outcomes after percutaneous coronary intervention: Effects of stenting and institutional volume shifts SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; BALLOON ANGIOPLASTY; ARTERY DISEASE; ASSOCIATION; PLACEMENT; HOSPITALS; IMPLANTATION; MORTALITY AB Background This study examines how the dissemination of stenting and procedural shifts to high-volume facilities have affected short-term outcomes after percutaneous coronary intervention (PCI). Methods Discharge information from the 1994 and 1997 US Nationwide Inpatient Sample was used. Data from 1994 involved 84,036 angioplasties, 27.3% of which were performed for acute myocardial infarction (AMI), at a time when stents were generally unavailable. Data from 1997 included 118,548 angioplasties, 30.2% of which were performed for AMI and 59% of which involved stenting. Outcomes included same-admission mortality and same-admission bypass grafting surgery (CABG). Results Compared with 1994, in 1997 stents were in widespread use, and there was a significant shift in PCI procedures to high-volume facilities. There was no significant difference in overall mortality rates between 1994 and 1997. However, same-admission CABG rates were lower in 1997 than in 1994 for the AMI group (2.9% vs,4.7%, P < .0001) and for the no-AMI group (1.8% vs 3.0%, P < .0001), which was attributable almost entirely to stenting. For 1997 only, patients receiving stents had a lower mortality rate than patients undergoing PCI without stenting (AMI 2.7% vs 4.7%, P < .0001, no AMI 0.7% vs 0.9%, P = .004). Conclusions Despite the dissemination of stenting and shifts to high-volume facilities, overall mortality rates after PCI have not significantly changed. However, patients undergoing stenting in 1997 had a significantly lower mortality rate than patients who did not undergo stenting, suggesting that stents may prevent inhospital deaths. Furthermore, same-admission CABG rates have decreased dramatically, an association seen with the introduction of stenting, but not with volume shifts. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. Hlth Serv Res & Dev, Seattle, WA USA. Dept Vet Affairs, Dept Med, Seattle, WA USA. RP Maynard, C (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 18 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 2002 VL 144 IS 2 BP 309 EP 314 DI 10.1067/mhj.2002.123845 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 585AR UT WOS:000177501400020 ER PT J AU Wang, TJ Larson, MG Levy, D Leip, EP Benjamin, EJ Wilson, PWF Sutherland, P Omland, T Vasan, RS AF Wang, TJ Larson, MG Levy, D Leip, EP Benjamin, EJ Wilson, PWF Sutherland, P Omland, T Vasan, RS TI Impact of age and sex on plasma natriuretic peptide levels in healthy adults SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; ESSENTIAL-HYPERTENSION; GENE-EXPRESSION; ECHOCARDIOGRAPHY; HYPERTROPHY; POPULATION; RECEPTOR; DISEASE; HUMANS; MARKER AB Assays for natriuretic peptides have received considerable attention as potential screening tests for congestive heart failure and left ventricular dysfunction. However, information regarding the impact of age, sex, and other physiologic characteristics on natriuretic peptide levels is limited. We examined a healthy reference sample of 911 subjects (mean age 55 years, 62% women) from the Framingham Heart Study who were free of hypertension, valvular disease, diabetes, atrial fibrillation, obesity, coronary heart disease, congestive heart failure, and renal failure, and who had normal left ventricular systolic function. Plasma brain natriuretic peptide and N-terminal atrial natriuretic peptide levels were measured, and multivariable regression used to assess correlates of natriuretic peptide levels. The strongest predictors of higher natriuretic peptide levels were older age and female sex. Other multivariable predictors included lower diastolic blood pressure (higher pulse pressure), lower body mass index, and higher left atrial size. Reference limits were then formulated based on the empirical distribution of natriuretic peptide levels by gender both across all ages and partitioned by age. Age-pooled reference limits compared with age-specific limits classified a higher proportion of healthy elderly subjects (17% vs 2.5%), but a lower proportion of healthy young subjects (1% vs 2.5%) as "abnormal." We conclude that interpretation of natriuretic peptide levels should take into consideration gender and possibly age. The reference limits derived from this large, healthy community-based sample will aid in the identification of elevated natriuretic peptide levels in clinical practice. (C) 2002 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Div,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Cardiol Sect, Div Endocrinol, Dept Med,Sch Med, Boston, MA 02215 USA. Natl Hosp Norway, Dept Cardiol, Oslo, Norway. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayne Ave, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01HL67288-01, K24 HL 04334-01A1, N01-HC-25195, R01 HL64753]; NINDS NIH HHS [R01-NS-17950] NR 29 TC 273 Z9 288 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2002 VL 90 IS 3 BP 254 EP 258 AR PII S0002-9149(02)02464-5 DI 10.1016/S0002-9149(02)02464-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 580QZ UT WOS:000177246400010 PM 12127613 ER PT J AU Scirica, BM Cannon, CP Antman, EM Murphy, SA Morrow, DA Sabatine, MS McCabe, CH Gibson, CM Braunwald, E AF Scirica, BM Cannon, CP Antman, EM Murphy, SA Morrow, DA Sabatine, MS McCabe, CH Gibson, CM Braunwald, E TI Validation of the thrombolysis in myocardial infarction (TIMI) risk sore for unstable angina pectoris and non-ST-elevation myocardial infarction in the TIMI III registry SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB The Thrombolysis In Myocardial Infarction (TIMI) risk score for unstable angina pectoris and non-ST-elevation myocardial infarction has been shown to be useful in risk stratification. For the first time, in unselected patients in the TIMI III Registry, we found that the risk score successfully predicted death, myocardial infarction, and/or recurrent ischemia at 6 weeks and 1 year; thus, it is an important tool for clinicians in assessing a patient's risk for adverse events and identifying patients who may benefit from more aggressive treatment. C1 Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. Harvard Clin Res Inst, Boston, MA USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 8 TC 50 Z9 51 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 AUG 1 PY 2002 VL 90 IS 3 BP 303 EP + AR PII S0002-9149(02)02468-2 DI 10.1016/S0002-9149(02)02468-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 580QZ UT WOS:000177246400015 PM 12127617 ER PT J AU McKeown, NM Meigs, JB Liu, SM Wilson, PWF Jacques, PF AF McKeown, NM Meigs, JB Liu, SM Wilson, PWF Jacques, PF TI Whole-grain intake is favorably associated with metabolic risk factors for type 2 diabetes and cardiovascular disease in the Framingham Offspring Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE whole grains; refined grains; risk factors; survey; Framingham Offspring Study; food-frequency questionnaire; type 2 diabetes; cardiovascular disease ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY HEART-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; IOWA WOMENS HEALTH; HIGH-FIBER DIETS; YOUNG-ADULTS; HIGH-CARBOHYDRATE; FASTING INSULIN; IMPROVE GLUCOSE; BLOOD-PRESSURE AB Background: The influence of whole grains on cardiovascular disease risk may be mediated through multiple pathways, eg, a reduction in blood lipids and blood pressure, an enhancement of insulin sensitivity, and an improvement in blood glucose control. Objective: The objective was to examine the association between diets rich in whole- or refined-grain foods and several metabolic markers of disease risk in the Framingham Offspring Study cohort. Design: Whole-grain intake and metabolic risk markers were assessed in a cross-sectional study of 2941 subjects. Results: After adjustment for potential confounding factors, whole-grain intake was inversely associated with body mass index ((x) over bar: 26.9 in the lowest and 26.4 in the highest quintile of intake; P for trend = 0.06), waist-to-hip ratio (0.92 and 0.91, respectively; P for trend = 0.005), total cholesterol (5.20 and 5.09 mmol/L, respectively; P for trend = 0.06), LDL cholesterol (3.16 and 3.04 mmol/L, respectively; P for trend = 0.02), and fasting insulin (205 and 199 pmol/L, respectively; P for trend = 0.03). There were no significant trends in metabolic risk factor concentrations across quintile categories of refined-grain intake. The inverse association between whole-grain intake and fasting insulin was most striking among overweight participants. The association between wholegrain intake and fasting insulin was attenuated after adjustment for dietary fiber and magnesium. Conclusion: Increased intakes of whole grains may reduce disease risk by means of favorable effects on metabolic risk factors. C1 Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Program Epidemiol, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Gen Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. RP Jacques, PF (reprint author), Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Program Epidemiol, 711 Washington St, Boston, MA 02111 USA. RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NHLBI NIH HHS [N01-HC-38038]; NIDDK NIH HHS [T32 DK 07651] NR 69 TC 287 Z9 298 U1 2 U2 20 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2002 VL 76 IS 2 BP 390 EP 398 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 577CV UT WOS:000177044900016 PM 12145012 ER PT J AU Huerta, S Rogers, LM Li, ZP Heber, D Liu, C Livingston, EH AF Huerta, S Rogers, LM Li, ZP Heber, D Liu, C Livingston, EH TI Vitamin A deficiency in a newborn resulting from maternal hypovitaminosis A after biliopancreatic diversion for the treatment of morbid obesity SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin A deficiency; biliopancreatic diversion; night blindness; malabsorption; morbid obesity; neonatal nutrition; hypovitaminosis A ID RETINOL-BINDING PROTEIN; NUTRITIONAL-STATUS; GASTRIC BYPASS; GESTATIONAL-AGE; A STATUS; PREGNANCY AB Background: Biliopancreatic diversion (BPD) has been advocated for the treatment of morbid obesity. This procedure has the theoretical advantage that patients retain normal eating capacity and lose weight irrespective of their eating habits. However, vitamin deficiencies may develop because BPD causes malabsorption. Objective: This report describes a 40-y-old mother and her newborn infant, who developed vitamin A deficiency as a result of iatrogenic maternal malabsorption after BPD. Our primary objective is to show that BPD patients need close follow-up and lifelong micronutrient supplementation to prevent nutrient deficiencies in themselves and their offspring. Design: The medical records of the mother and infant were reviewed, and their clinical course was followed until 10 mo postpartum. The mother was also interviewed on several occasions about her medical care, follow-up, and supplemental vitamin use. Results: The mother developed night blindness with undetectable serum vitamin A concentrations in the third trimester of her pregnancy. Her vitamin A deficiency was untreated until she delivered her infant. At delivery, the infant also had vitamin A deficiency. He may have permanent retinal damage, but this is still unclear because the ophthalmologic examination performed at 2 mo of age was inconclusive. Conclusions: Complications of BPD may take many years to develop, and the signs and symptoms may be subtle. Because of the malabsorption that results from BPD, patients need lifelong follow-up and appropriate vitamin supplementation to prevent deficiencies. These nutrient deficiencies can also affect the offspring of female BPD patients. 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 USA. RP Huerta, S (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, 900 Vet Ave,12-217 Warren Hall,Box 951742, Los Angeles, CA 90095 USA. FU NIDDK NIH HHS [DK07688] NR 22 TC 52 Z9 54 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2002 VL 76 IS 2 BP 426 EP 429 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 577CV UT WOS:000177044900021 PM 12145017 ER PT J AU Meininger, G Hadigan, C Rietschel, P Grinspoon, S AF Meininger, G Hadigan, C Rietschel, P Grinspoon, S TI Body-composition measurements as predictors of glucose and insulin abnormalities in HIV-positive men SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE HIV; insulin; lipodystrophy; visceral fat; waist-to-hip ratio; WHR; body composition; men ID INFECTED PATIENTS; FAT DISTRIBUTION; FASTING HYPERINSULINEMIA; PROTEASE INHIBITOR; RISK-FACTORS; METABOLIC ABNORMALITIES; HIV-1-INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; COMPUTED-TOMOGRAPHY; HEART-DISEASE AB Background: Fat redistribution and metabolic abnormalities are seen increasingly in HIV-positive patients. However, the degree to which abnormalities in fat distribution predict glucose and insulin concentrations in these patients remains unknown. Objective: We determined how well measurements of fat distribution derived from anthropometry, dual-energy X-ray absorptiometry, and computed tomography predicted hyperinsulinemia in HIV-positive men. Design: Body-composition data were analyzed in 41 HIV-positive men (21 with fat redistribution and 20 without) and 20 HIV-negative control subjects matched for age and body mass index (BMI). Multivariate modeling was performed to determine the effects of body composition on fasting insulin and insulin area under the curve (AUC) during standard glucose tolerance testing. Results: WHR was superior to other body-composition measures in predicting fasting hyperinsulinemia and was a strong predictor of insulin AUC in HIV-positive men. Fasting insulin increased by 77.4 pmol/L for each 0.1-unit change in WHR (95% CI: 18.6, 136.1; P = 0.011), overall r(2) = 0.415 in a model also including age, BMI, and protease inhibitor use. Measures of intraabdominal and subcutaneous fat did not predict fasting hyperinsulinemia but were independent predictors of insulin AUC in multivariate modeling. The ratio of visceral to subcutaneous abdominal fat predicted the largest degree of variance in insulin AUC. Conclusions: Fat redistribution contributes to hyperinsulinemia in HIV-positive men, independent of BMI and protease inhibitor use. WHR is an integrated index of body-composition changes and strongly predicts both fasting hyperinsulinemia and insulin AUC in HIV-positive men. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [K23-DK02844, R01-DK59535] NR 33 TC 47 Z9 47 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2002 VL 76 IS 2 BP 460 EP 465 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 577CV UT WOS:000177044900027 PM 12145023 ER PT J AU Van Cott, EM Smith, EY Galanakis, DK AF Van Cott, EM Smith, EY Galanakis, DK TI Elevated fibrinogen in an acute phase reaction prolongs the reptilase time but typically not the thrombin time SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE fibrinogen; acute phase reaction; reptilase time; thrombin time; dysfibrinogenemia ID DYSFIBRINOGENEMIA; DISEASE AB The effects of elevated fibrinogen on thrombin and reptilase times have not been well documented. High fibrinogen levels are common (38% of specimens submitted to our coagulation laboratory). Among 102 patients in the present study an endogenously elevated fibrinogen level was Significantly associated, as follows, with prolonged reptilase times: 1 (4%) of 28 with normal fibrinogen levels, 6 (20%) of 30 with levels in the 400 to 700 mg/dL (4.0-7.0 g/L) range, 10 (34%) of 29 with levels in the 700 to 1, 000 mg/dL (7.0-10.0 g/L) range, and 7 (47%) of 15 with fibrinogen levels greater than 1,000 mg/dL (10.0 g/L). This association was independent of patient age and fibrin degradation product titer. In contrast, thrombin time was not altered notably by elevated fibrinogen levels. In 4 patients studied further the prolonged clotting times could be corrected or nearly corrected by adding calcium chloride or albumin, whereas no such corrections were demonstrable in samples from several hereditary dysfibrinogenemia control subjects. An elevated fibrinogen level is common and is associated with reptilase time prolongations. For patients with prolonged reptilase times, a fibrinogen assay is suggested before establishing a diagnosis of dysfibrinogenemia. C1 Massachusetts Gen Hosp, Dept Pathol, Coagulat Lab, Boston, MA 02114 USA. SUNY Stony Brook, Blood Transfus Serv, Stony Brook, NY 11794 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Coagulat Lab, Gray Jackson 235,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 8 Z9 8 U1 0 U2 1 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 AUG PY 2002 VL 118 IS 2 BP 263 EP 268 PG 6 WC Pathology SC Pathology GA 577KQ UT WOS:000177060400018 PM 12162688 ER PT J AU Straus, WL Ofman, JJ MacLean, C Morton, S Berger, ML Roth, EA Shekelle, P AF Straus, WL Ofman, JJ MacLean, C Morton, S Berger, ML Roth, EA Shekelle, P TI Do NSAIDs cause dyspepsia? A meta-analysis evaluating alternative dyspepsia definitions SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; HEALTHY-VOLUNTEERS; GASTROINTESTINAL COMPLICATIONS; COLLABORATIVE METAANALYSIS; GASTRODUODENAL MUCOSA; RHEUMATOID-ARTHRITIS; HELICOBACTER-PYLORI; GASTRIC-MUCOSA AB OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with dyspepsia, but the relationship is obscured by variations in the terminology used to report GI symptoms. Using alternative definitions, we assessed the relationship between NSAID use and dyspepsia. METHODS: We searched MEDLINE, EMBASE, HEALTH-STAR, and BIOSIS databases (1966-1997) and New Drug Application reviews, identifying randomized, placebo-controlled trials (5 days or more duration) of any NSAID, reporting original data on GI complications. Based upon reported terms describing upper GI symptoms, we derived three definitions: strict, using terms synonymous with epigastric pain/discomfort; loose, (containing the strict definition plus terms for heartburn, nausea, bloating, anorexia, and vomiting); and a loose definition without heartburn terms (the loose-less-heartburn definition). Using each definition, we performed a random-effects model meta-analysis of the relationship between NSAID exposure and dyspepsia. RESULTS: Fifty-five published and 37 unpublished controlled NSAID trials met our inclusion criteria. The mean duration of the trials was 33.2 days (SD 40 days). Application of the strict definition resulted in a pooled risk ratio of dyspepsia for NSAIDs compared with placebo of 1.36 (95% CI = 1.11-1.67). For the loose definition, the pooled risk ratio was 1.13 (95% CI = 0.98-1.32). The loose-less-heartburn definition yielded a pooled risk ratio of 1.19 (95% CI = 1.03-1.39). In the placebo-treated control groups, the percent of patients reporting dyspepsia ranged from 2.3% (strict definition) to 4.2% (loose and loose-less-heartburn definitions). CONCLUSIONS: Using the strict definition, based solely on epigastric pain-related symptoms, NSAIDs increased the risk of dyspepsia by 36% (p < 0.05). These findings may be useful in creating a standardized definition of NSAID-related dyspepsia. C1 Merck & Co Inc, Outcomes Res & Management, W Point, PA 19486 USA. AHCPR So Calif Evidence Based Practice Ctr, Los Angeles, CA USA. Cedars Sinai Hlth Syst, Dept Med, Div Gastroenterol, Los Angeles, CA USA. Cedars Sinai Hlth Syst, Dept Hlth Serv Res, Div Gastroenterol, Los Angeles, CA USA. Cedars Sinai Hlth Syst, Zynx Hlth, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. W Los Angeles Vet Adm Med Ctr, Dept Med, Los Angeles, CA USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Straus, WL (reprint author), Merck & Co Inc, Outcomes Res & Management, Box 4,WP39-160, W Point, PA 19486 USA. NR 80 TC 46 Z9 47 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2002 VL 97 IS 8 BP 1951 EP 1958 AR PII S0002-9270(02)04262-4 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 584GV UT WOS:000177459600020 PM 12190159 ER PT J AU Fung, F Sherrard, DJ Gillen, DL Wong, C Kestenbaum, B Seliger, S Ball, A Stehman-Breen, C AF Fung, F Sherrard, DJ Gillen, DL Wong, C Kestenbaum, B Seliger, S Ball, A Stehman-Breen, C TI Increased risk for cardiovascular mortality among malnourished end-stage renal disease patients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE nutrition; cardiovascular disease (CVD); mortality; epidemiology ID C-REACTIVE PROTEIN; HEMODIALYSIS-PATIENTS; SERUM-ALBUMIN; DIALYSIS PATIENTS; HEART-DISEASE; INFLAMMATION; INTERLEUKIN-6; FAILURE; DEATH; HYPOALBUMINEMIA AB Background: Studies have shown that protein-energy malnutrition (PEM) is a strong predictor of total mortality among patients with end-stage renal disease (ESRD). The aim of this study is to assess the relationship between nutritional indices and cardiovascular (CV) mortality among patients with ESRD by using data from the US Renal Data System (USRDS) Dialysis Morbidity and Mortality Study Wave I (DMMS-1). Methods: Demographic and medical data were abstracted from 5,058 patients who participated in the USRDS DMMS-1. Nutritional measurements of interest included subjective assessment of malnutrition, serum albumin level, body mass index (BMI), and cholesterol level. The USRDS provided follow-up data on mortality through July 1998. The Cox proportional hazard model was used to estimate the risk for CV death associated with nutritional markers. Results: The risk for CV death was 39% greater for each 1-g/dL (10-g/L) decrement in serum albumin level (95% confidence interval [Cl], 1.20 to 1.60; P < 0.001). A care provider's assessment of malnutrition was associated with a 27% greater risk for CV mortality (95% Cl, 1.08 to 1.50; P < 0.004). For each one-unit decrement in BMI, the risk for CV disease (CVD) was 6% greater (95% Cl, 1.00 to 1.13; P < 0.046). Among patients without CVD at the study start, serum albumin level remained a significant risk factor for CV death (adjusted relative risk = 1.39 per 1-g/dL (10-g/L) increment; P = 0.026). In addition, change in albumin levels over time was significantly associated with CV mortality. For each 0.1-g/dL (1-g/L) decrement in albumin level per month, the risk for CV death was 2.24-fold greater (95% Cl, 1.65 to 3.02; P < 0.001) among the entire cohort and 3.86-fold greater (95% Cl, 1.96 to 7.60; P < 0.010) among those without a known history of CVD at the study start. Conclusion: Both PEM at baseline and worsening PEM over time are associated with a greater risk for CV death. This finding persists among dialysis patients without preexisting CVD at baseline. (C) 2002 by the National Kidney Foundation, Inc. C1 Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Div Nephrol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98108 USA. RP Stehman-Breen, C (reprint author), VA Puget Sound Hlth Care Syst, Div Nephrol, 1660 S Columbian Way,Mailstop 111A, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK07721-06] NR 34 TC 85 Z9 100 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2002 VL 40 IS 2 BP 307 EP 314 DI 10.1053/ajkd.2002.34509 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 578QN UT WOS:000177129800011 PM 12148103 ER PT J AU Stafford, RS Radley, DC AF Stafford, RS Radley, DC TI The potential of pill splitting to achieve cost savings SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID TABLET AB Objectives: To present a methodology for identifying specific medications for which pill splitting is clinically appropriate and cost saving, to present data from a commercial managed care population on current pill-splitting practices, and to estimate additional cost savings from extended use of this strategy. Study Design: Retrospective pharmacy claims analysis Methods: Pharmacy claims data from a commercial managed care health plan covering 19,000 lives and national drug data were used to compile a list of frequently prescribed medications. Excluding medications in which packaging, formulation, and potential adverse pharmacologic outcomes prohibited splitting, we performed a cost analysis of medications amenable to splitting. Results: Eleven medications amenable to pill splitting were identified based on potential cost savings and clinical appropriateness: clonazepam, doxazosin, atorvastatin, pravastatin, citalopram, sertraline, paroxetine, lisinopril, nefazadone, olanzapine, and sildenafil. For these medications, pill splitting is currently infrequent, accounting for annual savings of $6200 (or $0.03 per member per month), just 2% of the potential $259,500 (or $1.14 per member per month) that more comprehensive pill-splitting practices could save annually. Conclusions: Pill splitting can be a cost-saving practice when implemented judiciously using drug- and patient-specific criteria aimed at clinical safety, although this strategy is used infrequently. C1 Stanford Univ, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Stafford, RS (reprint author), Stanford Univ, Stanford Ctr Res Dis Prevent, 1000 Welch Rd, Palo Alto, CA 94304 USA. NR 10 TC 26 Z9 27 U1 0 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 AUG PY 2002 VL 8 IS 8 BP 706 EP 712 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 587JP UT WOS:000177637000004 PM 12212758 ER PT J AU Berg, AO Allan, JD Frame, PS Homer, CJ Lieu, TA Mulrow, CD Peipert, JF Pender, NJ Sox, HC Teutsch, SM Westhoff, C Woolf, SH AF Berg, AO Allan, JD Frame, PS Homer, CJ Lieu, TA Mulrow, CD Peipert, JF Pender, NJ Sox, HC Teutsch, SM Westhoff, C Woolf, SH CA Preventive Services Task Force TI Screening for bacterial vaginosis in pregnancy: Recommendations and rationale SO AMERICAN JOURNAL OF NURSING LA English DT Article C1 Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, Sch Nursing, San Antonio, TX USA. Univ Rochester, Cohocton, NY USA. Natl Initiat Childrens Healthcare Qual, Boston, MA USA. Natl Initiat Childrens Healthcare Qual, Boston, MA USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, San Antonio, TX USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. Merck & Co Inc, Outcomes Res & Management, W Point, PA USA. Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY USA. Virginia Commonwealth Univ Med Coll Virginia, Dept Family Practice, Fairfax, VA USA. RP Berg, AO (reprint author), Care of Atkins D, Agcy Healthcare Res & Qual, Ctr Practice & Technol Assessment, 6010 Execut Blvd,Suite 300, Rockville, MD 20852 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD AUG PY 2002 VL 102 IS 8 BP 91 EP 93 PG 3 WC Nursing SC Nursing GA 585TH UT WOS:000177540300044 PM 12394084 ER PT J AU To, K Adamian, M Dryja, TP Berson, EL AF To, K Adamian, M Dryja, TP Berson, EL TI Histopathologic study of variation in severity of retinitis pigmentosa due to the dominant rhodopsin mutation Pro23His SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID GENE AB PURPOSE: To compare histopathologic findings in an autopsy eye of an 87-year,old woman with retinitis pigmentosa and the rhodopsin mutation Pro23His with findings in an autopsy eye of a 77-year old female relative (first cousin) with retinitis pigmentosa and the same mutation. DESIGN: Histopathologic study. METHODS: One eye from each patient was prepared for light and electron microscopy within 5 hours after death. Photoreceptor nuclear counts were performed. RESULTS: Photoreceptor degeneration and intraretinal bone spicule pigmentation were evident in both cases. The younger patient had more extensive photoreceptor loss and more intraretinal pigmentation than her older relative. CONCLUSION: A marked variation in the extent of retinal degeneration can be seen in two relatives with retinitis pigmentosa and rhodopsin, Pro23His. This study sup. ports the idea that factors other than the primary gene defect are responsible for the severity of this condition. (C) 2002 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Bernard Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. RP Berson, EL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Bernard Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 18 Z9 19 U1 0 U2 0 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 AUG PY 2002 VL 134 IS 2 BP 290 EP 293 DI 10.1016/S0002-9394(02)01545-3 PG 4 WC Ophthalmology SC Ophthalmology GA 579GB UT WOS:000177169300029 PM 12140048 ER PT J AU Poulaki, V Mitsiades, CS Kotoula, V Tseleni-Balafouta, S Ashkenazi, A Koutras, DA Mitsiades, N AF Poulaki, V Mitsiades, CS Kotoula, V Tseleni-Balafouta, S Ashkenazi, A Koutras, DA Mitsiades, N TI Regulation of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in thyroid carcinoma cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TRAIL-INDUCED APOPTOSIS; FLICE-INHIBITORY PROTEIN; FAS-MEDIATED APOPTOSIS; PROSTATE-CANCER CELLS; EWINGS-SARCOMA FAMILY; NK CELLS; SIGNAL-TRANSDUCTION; FOLLICULAR CELLS; TUMOR-CELLS; TNF FAMILY AB Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/Apo2 ligand selectively kills neoplastic cells, including thyroid carcinoma cells (Mitsiades et al: Thyroid carcinoma cells are resistant to FAS-mediated apoptosis but sensitive to tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res 2000, 60:412241299). We investigated the mechanisms regulating Apo2L/TRAIL-induced apoptosis in thyroid carcinoma cells, as well as the impact of insulin-like growth factor (IGF)-1, interferon-gamma, and TNF-alpha. We found that die emergence of resistance to Apo2L/TRAIL, after prolonged incubation with this cytokine, was associated with increased levels of RICE inhibitory protein (FLIP), and was overcome by cycloheximide and bisindolylmaleimide, that specifically down-regulated FLEP expression, as well as by transfection of a FLIP anti-sense oligonucleotide. IGF-1 activated Akt; up-regulated the caspase inhibitors FLEP, cIAP-2, XIAP, and survivin; and attenuated Apo2L/TRAIL-induced apoptosis. This effect was inhibited by the IGF-1 receptor neutralizing antibody aIR3, the PI-3K inhibitor wortmannin, and the heat shock protein-90 chaperone inhibitor geldanamycin. Transfection of constitutively active Akt protected from TRAIL. Conversely, interferon-gamma and TNF-alpha had a sensitizing effect. We conclude that FLEP may negatively regulate Apo2L/TRAIL-induced apoptosis in thyroid carcinomas. Microenvironmental paracrine survival factors, such as IGF-1, up-regulate caspase inhibitors, including FLEP, and protect from Apo2L/TRAIL in a PI-3K/Akt-dependent manner. T helper-1 cytokines and compounds that selectively abrogate the IGF-1 signaling pathway may he helpful adjunct agents in Apo2L/TRAIL-based anti-cancer therapeutic regimens. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Aristotle Univ Thessaloniki, Sch Med, Dept Pathol, GR-54006 Thessaloniki, Greece. Evgenid Hosp, Endocrine Unit, Athens, Greece. Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA. RP Poulaki, V (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 325 Cambridge St, Boston, MA 02114 USA. NR 64 TC 57 Z9 67 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 AUG PY 2002 VL 161 IS 2 BP 643 EP 654 DI 10.1016/S0002-9440(10)64220-4 PG 12 WC Pathology SC Pathology GA 582DQ UT WOS:000177334800033 PM 12163389 ER PT J AU Silver, JK Aiello, DD AF Silver, JK Aiello, DD TI Polio survivors - Falls and subsequent injuries SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE polio; polio survivors; falls; fracture ID OLDER PERSONS; OSTEOPOROTIC FRACTURES; ENVIRONMENTAL HAZARDS; ELDERLY PEOPLE; HOME; POPULATION; POLIOMYELITIS; PREVENTION; ADULTS AB Objective: This study examines the frequency of falls in polio survivors and their resulting morbidity. Design: Two groups, fallers vs. nonfallers, were investigated in this descriptive study. A total of 233 polio survivors volunteered to complete a structured questionnaire on fall history and sequelae. Results: Of the study participants, 64% had fallen within the previous year, and 61% had falls for which they received medical attention, including 35% who had at least one fracture. There was not a correlation between age and falling, but there was a strong correlation between tripping and falling. Conclusions: Falls with resultant injuries are a significant issue for polio survivors that warrants further study. Because tripping was predictive of falling in this sample, bracing should be considered as a treatment or preventative measure. C1 Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Physiatry, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Spaulding Framingham Outpatient Ctr, Boston, MA USA. RP Silver, JK (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, 570 Worcester Rd, Framingham, MA 01702 USA. NR 27 TC 21 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2002 VL 81 IS 8 BP 567 EP 570 AR UNSP 0894-9115/02/8108-0567/0 DI 10.1097/00002060-200208000-00002 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 577EE UT WOS:000177047900002 PM 12172064 ER PT J AU Pagel, KJ Kaul, MP Dryden, JD AF Pagel, KJ Kaul, MP Dryden, JD TI Lack of utility of Semmes-Weinstein monofilament testing in suspected carpal tunnel syndrome SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE carpal tunnel syndrome; Semmes-Weinstein monofilaments; electrodiagnosis; veteran AB Objective: To investigate the value of Semmes-Weinstein monofilament (SWM) testing in patients with electrodiagnostically confirmed carpal tunnel syndrome in a group of patients with symptoms compatible with carpal tunnel syndrome. Design: A total of 119 consecutive patients with symptoms compatible with carpal tunnel syndrome were assessed. Blinded comparison of two Semmes-Weinstein monofilament testing protocols with orthodromic midpalm electrodiagnostic testing was performed. The electrodiagnostic test was considered the standard to which the results of the Semmes-Weinstein monofilament testing were measured. Results: Fifty three percent of our patients had electrodiagnostically confirmed carpal tunnel syndrome. Using a conservative Semmes-Weinstein monofilament testing protocol the sensitivity was 98% and the specificity was 15%. The positive predictive value was 56% and the negative predictive value was 88%. Using a liberal Semmes-Weinstein monofilament testing protocol the sensitivity was 13% and the specificity was 88%. The positive predictive value was 53% and the negative predictive value was 47%. Conclusion: Semmes-Weinstein monofilament testing was not shown to have utility in diagnosing electrodiagnostically confirmed carpal tunnel syndrome in our population of predominantly male veterans. C1 Portland Vet Affairs Med Ctr, Rehabil Med Serv, Portland, OR 97207 USA. RP Kaul, MP (reprint author), Portland Vet Affairs Med Ctr, Rehabil Med Serv, 3710 US Vet Hosp Rd, Portland, OR 97207 USA. NR 12 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2002 VL 81 IS 8 BP 597 EP 600 AR UNSP 0894-9115/02/8108-0597/0 DI 10.1097/00002060-200208000-00007 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 577EE UT WOS:000177047900007 PM 12172069 ER PT J AU Lucey, BC Maher, MM Boland, GW Gervais, DA Mueller, PR AF Lucey, BC Maher, MM Boland, GW Gervais, DA Mueller, PR TI Percutaneous treatment by interventional radiologists of anastomotic leaks: Basic concepts SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ABSCESS DRAINAGE C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. RP Lucey, BC (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. NR 6 TC 6 Z9 6 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 AUG PY 2002 VL 179 IS 2 BP 365 EP 369 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 575EY UT WOS:000176934900011 PM 12130433 ER PT J AU Hulka, CA Hall, DA McCarthy, K Simeone, J AF Hulka, CA Hall, DA McCarthy, K Simeone, J TI Sonographic findings in patients with adenomyosis: Can sonography assist in predicting extent of disease? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DIFFUSE ADENOMYOSIS; TRANSVAGINAL ULTRASONOGRAPHY; DIFFERENTIAL-DIAGNOSIS; UTERINE ADENOMYOSIS; MR; LEIOMYOMA; UTERUS AB OBJECTIVE. We assessed whether specific sonographic characteristics are indicative of the extent of adenomyosis and whether fibroids alter this assessment. MATERIALS AND METHODS. Patients' records were evaluated for the diagnosis of adenomyosis determined by hysterectomy and for sonography performed within 2 months of surgery. Seventy-three sonograms were evaluated by sonologists without knowledge of the extent of adenomyosis. Sonographic categories included visualization of the endometrium, presence of a diffuse uterine process, presence of fibroids, and normal findings. Pathologic results included mild, focal, and severe adenomyosis. Histologic and sonographic categories were correlated using the chi-square and Fisher's exact tests. RESULTS. Forty-six specimens contained mild adenomyosis, 18 contained severe disease, and nine contained focal disease. Forty-one specimens contained fibroids. The endometrium was visualized in 10 cases of severe adenomyosis, seven cases of adenomyoma, and 35 cases of mild disease. Visualization of the endometrium did not relate to the severity of disease (p = 0.6). Of 18 cases of severe disease, 13 sonograms showed a diffuse process. Of nine cases of adenomyomas, no sonograms showed a diffuse process; and of 46 cases of mild disease, nine sonograms showed a diffuse process. A diffuse process was related to the severity of adenomyosis (p < 0.001). When fibroids were present, a diffuse process did not relate to the extent of adenomyosis (p = 0.01). CONCLUSION. In the absence of focal fibroids, a diffuse uterine process seen on sonography relates to the severity of adenomyosis. Fibroids limit the ability to diagnose the severity of adenomyosis. The visualization of the endometrium does not relate to the severity of adenomyosis. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Hulka, CA (reprint author), Cambridge Hlth Alliance, Dept Radiol, 1493 Cambridge St, Cambridge, MA 02139 USA. NR 16 TC 15 Z9 17 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 AUG PY 2002 VL 179 IS 2 BP 379 EP 383 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 575EY UT WOS:000176934900014 PM 12130436 ER PT J AU Prasad, SR Wittram, C Shepard, JA McLoud, T Rhea, J AF Prasad, SR Wittram, C Shepard, JA McLoud, T Rhea, J TI Standard-dose and 50%-reduced-dose chest CT: Comparing the effect on image quality SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID HIGH-RESOLUTION CT; HELICAL CT; TUBE CURRENT; REDUCTION; CHILDREN; CANCER AB OBJECTIVE. CT accounts for considerable population-based radiation dose from radiographic diagnostic studies. The technical factors for CT examinations are not appropriately adjusted on the basis of patient size and anatomy. We hypothesized that radiation doses for routine chest CT can be reduced by 50% for the evaluation of normal structures without seriously jeopardizing image quality. SUBJECTS AND METHODS. After receiving institutional review board approval, we prospectively studied 24 patients with cancer who were 65 years old and older on a multidetector CT scanner. Each patient underwent imaging with four slices (centered at the carina) at the standard dose (220-280 mAs) and at 50%-reduced dose (110-140 mAs) at a constant 140 kVp. Single breath-hold scanning was performed with a 2.5-mm detector configuration, a tube rotation time of 0.8 sec, and a pitch of 6:1. Contiguous images were reconstructed at 5-mm intervals. Two subspecialty-trained chest radiologists who were unaware of the CT technique reviewed randomized images for overall image quality and anatomic detail of the structures in the lung, airway, mediastinum, and chest wall using a 5-point scale (1, worst; 2, suboptimal; 3, adequate; 4, very good; 5, excellent). The data were analyzed using the Wilcoxon's signed rank test. RESULTS. Although overall image quality was better with standard-dose CT, the quality of reduced-dose CT was acceptable. The differences in mean scores were statistically significant. There was a correlation of 0.59 between observers. The mean scores of standard-dose CT were always greater than or equivalent to those of low-dose CT for both observers. The assessment of great vessels and soft tissue of the chest wall contributed mainly to the differences in image quality. Both the central and peripheral lung parenchyma and the airway were adequately visualized on low-dose CT. Radiation doses (based on weighted-CT-dose index) from standard-dose CT and 50%-reduced-dose CT were 15.6-21.4 mSv and 7.8-10.7 mSv, respectively (from the manufacturer's data). CONCLUSION. Chest CT image quality appears to be acceptable for evaluating normal anatomic structures even with a 50% reduction in radiation dose. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP McLoud, T (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders 216,55 Fruit St, Boston, MA 02114 USA. NR 26 TC 76 Z9 103 U1 1 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2002 VL 179 IS 2 AR UNSP 0361-803X/02/1792-461 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 575EY UT WOS:000176934900028 PM 12130452 ER PT J AU Nurgalieva, ZZ Malaty, HM Graham, DY Almuchambetova, R Machmudova, A Kapsultanova, D Osato, MS Hollinger, FB Zhangabylov, A AF Nurgalieva, ZZ Malaty, HM Graham, DY Almuchambetova, R Machmudova, A Kapsultanova, D Osato, MS Hollinger, FB Zhangabylov, A TI Helicobacter pylori infection in Kazakhstan: Effect of water source and household hygiene SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID LIVING-CONDITIONS; RISK-FACTORS; HEPATITIS-A; CHILDREN; TRANSMISSION; SEROPREVALENCE; PREVALENCE; COMMUNITY; SEROEPIDEMIOLOGY; EPIDEMIOLOGY AB The epidemiology of Helicobacter pylori infection and risk factors associated with its transmission are not well understood. Kazakhstan is country with two ethnic groups, Asian (Kazakhs) and Western (Russians), living under similar socioeconomic conditions. The aim of this study was to examine the seroepidemiologic pattern of H. pylori and hepatitis A among the same individuals from both ethnic groups, with emphasis on water source and household sanitation practices. This was a cross-sectional seroepidemiologic study conducted among unrelated healthy individuals in Kazakhstan. From May through August 1999, individuals between the ages of 10 and 60 years from Almaty, Kazakhstan, were invited to participate. Demographic information, socioeconomic factors, living conditions, and various aspects of the local household environment including access to water were collected. A clean water index (CWI) was created based on combined factors, consistency of boiling water before drinking, frequency of storing and reusing water, and frequency of bathing and showering. H. pylori and hepatitis A antibodies were assessed by enzyme-linked immunosorbent assay. Two hundred eighty-eight individuals between the ages of 10 and 60 years participated. The prevalence of H. pylori infection was almost identical among the two ethnic groups (Russians 79% and Kazakhs 80%). H. pylori infection was inversely correlated with the CWI (i.e., 56%, 79%, and 95% for high, middle, and low, respectively (P<.05). Drinking river water had highest risk of H. pylori infection (OR = 13.6, 95% CI = 1.8- 102.4; P<.01, compared with tap water). Crowding showed no significant effect on H. pylori prevalence. Anti-HAV antibodies were found in 86% of the population, 90% among the Russians versus 82% among the Kazakhs (OR = 1.8, 95 % CI = 1.1-3.8, P=.05). Although the two infections were highly correlated (P<.001), antibody to both infections were present simultaneously in only 74%. The prevalence of H. pylori infection in Kazakhstan is very high. The data suggest that transmission of H. pylori can be water borne, related to poor sanitary practices, or both. The high prevalence of antibodies to H. pylori and HAV among this population is a marker for poor sanitation and hygienic practices. Reducing the rate of H. pylori transmission will require improvements in overall sanitation including clean water, waste disposal, as well as in household hygienic practices. C1 VA Med Ctr, Dept Med, Houston, TX 77030 USA. Almaty State Med Univ, Dept Fac Therapy, Almaty, Kazakhstan. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Nurgalieva, ZZ (reprint author), VA Med Ctr, Dept Med, Rm 3A-320 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [DK-53659, DK56338] NR 39 TC 62 Z9 65 U1 2 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD AUG PY 2002 VL 67 IS 2 BP 201 EP 206 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 601ZN UT WOS:000178479700015 PM 12389948 ER PT J AU Raines, DE Claycomb, RJ AF Raines, DE Claycomb, RJ TI The role of electrostatic interactions in governing anesthetic action on the Torpedo nicotinic acetylcholine receptor SO ANESTHESIA AND ANALGESIA LA English DT Article ID GATED ION CHANNELS; LOG K-VALUES; POSTSYNAPTIC MEMBRANES; INHALED ANESTHETICS; AGONIST AFFINITY; NARCOSIS; TETRACHLOROMETHANE; DESENSITIZATION; COMPLEXATION; POTENCIES AB lsoflurane and normal alkanols reduce the apparent agonist dissociation constant (K-d) of the nicotinic acetylcholine receptor (nAChR) at clinically relevant concentrations, whereas cyclopropane and butane do not. This suggests that electrostatic (hydrogen bonding and/or dipolar) interactions modulate anesthetic potency in this model receptor system. To further define the nature of these interactions, we quantified the potencies with which a heterologous group of general anesthetics reduces the nAChR's apparent K-d for acetylcholine. We assessed the importance that an anesthetic's molecular volume, ability to donate a hydrogen bond (hydrogen bond acidity), ability to accept a hydrogen bond (hydrogen bond basicity), and dipole moment play in determining aqueous potency. We found that aqueous anesthetic potency increases with molecular volume and decreases with hydrogen bond basicity but is unaffected by dipole moment and hydrogen bond acidity. These results suggest that anesthetics reduce the apparent agonist K-d of the nAChR by binding to a site that has a dipolarity and ability to accept hydrogen bonds that are similar to those of water, but a hydrogen bond-donating capacity that is less. C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, 32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01-GM61927] NR 24 TC 6 Z9 6 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 AUG PY 2002 VL 95 IS 2 BP 356 EP 361 DI 10.1213/01.ANE.0000019433.96198.B1 PG 6 WC Anesthesiology SC Anesthesiology GA 575TH UT WOS:000176964200021 PM 12145051 ER PT J AU Cluff, R Mehio, AK Cohen, SP Chang, YC Sang, CN Stojanovic, MP AF Cluff, R Mehio, AK Cohen, SP Chang, YC Sang, CN Stojanovic, MP TI The technical aspects of epidural steroid injections: A national survey SO ANESTHESIA AND ANALGESIA LA English DT Article ID LOW-BACK-PAIN; SCIATICA; EFFICACY; TRIALS AB Although epidural steroid injections (ESIs) are a common treatment for chronic pain conditions, it is not clear whether there is consensus on their technical aspects. The current literature suggests that variations in technical aspects may affect ESI outcomes. The goal of the survey was to help establish a standard frame of reference for the performance of ESIs. We analyzed survey results from 68 academic anesthesia programs and 28 private practices in the United States. The main finding in this survey is that there is no clear-cut consensus as to the ideal method to perform ESI. There is a wide variation among individual practices in almost every technical aspect of ESI. Private practices use significantly more fluoroscopy than academic centers. The large difference was found in the cervical region where 73% of private practices and only 39% of academic institutions polled perform the ESIs with fluoroscopic guidance (P = 0.005). A similar discrepancy was found in approaches to the epidural space after laminectomy where 61% of private practices, but only 15% of academic centers, use the transforaminal approach. The study results indicate that there is no consensus, and that there is a wide variation in current practices. C1 Massachusetts Gen Hosp, MGH Pain Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Trials Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Intervent Pain Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stojanovic, MP (reprint author), Massachusetts Gen Hosp, MGH Pain Ctr, ACC-324,Fruit St, Boston, MA 02114 USA. NR 25 TC 65 Z9 69 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 AUG PY 2002 VL 95 IS 2 BP 403 EP 408 DI 10.1213/01/ANE.0000020189.99898.E3 PG 6 WC Anesthesiology SC Anesthesiology GA 575TH UT WOS:000176964200031 PM 12145061 ER PT J AU Anhoury, P Nathanson, D Hughes, CV Socransky, S Feres, M Chou, LSL AF Anhoury, P Nathanson, D Hughes, CV Socransky, S Feres, M Chou, LSL TI Microbial profile on metallic and ceramic bracket materials SO ANGLE ORTHODONTIST LA English DT Article DE microbiota; metallic brackets; ceramic brackets; "Checkerboard" DNA-DNA hybridization ID STREPTOCOCCUS-MUTANS; ORTHODONTIC APPLIANCES; PLAQUE; CHECKERBOARD; PREVALENCE AB The placement of orthodontic appliances creates a favorable environment for the accumulation of a microbiota and food residues, which, in time, may cause caries or exacerbate any pre-existing periodontal disease. The purpose of the present study was to compare the total bacterial counts present on metallic and ceramic orthodontic brackets in order to clarify which bracket type has a higher plaque retaining capacity and to determine the levels of Streptococcus mutans and Lactobacillus spp on both types of brackets. Thirty-two metallic brackets and 24 ceramic brackets were collected from orthodontic patients at the day of debonding. Two brackets were collected from each patient; one from a maxillary central incisor and another from a maxillary second premolar. Sixteen patients who used metallic brackets and 12 patients who used ceramic brackets were sampled. Bacterial populations were studied using "checkerboard" DNA-DNA hybridization, which uses DNA probes to identify species in complex microbial samples. The significance of differences between groups was determined using the Mann-Whitney U-test. Results showed no significant differences between metallic and ceramic brackets with respect to the caries-inducing S mutans and L acidophilus spp counts. Mean counts of 8 of 35 additional species differed significantly between metallic and ceramic brackets with no obvious pattern favoring one bracket type over the other. This study showed higher mean counts of Treponema denticola, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum ss vincentii, Streptococcus anginosus, and Eubacterium nodatum on metallic brackets while higher counts of Eikenella corrodens, Campylobacter showae, and Selenomonas noxia were found on ceramic brackets. C1 Boston Univ, Goldman Sch Dent Med, Div Oral Med, Dept Restorat Sci Biomat, Boston, MA 02118 USA. Boston Univ, Goldman Sch Dent Med, Div Oral Med, Dept Orthodont, Boston, MA 02118 USA. Boston Univ, Goldman Sch Dent Med, Dept Pediat Dent, Boston, MA 02118 USA. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Chou, LSL (reprint author), Boston Univ, Goldman Sch Dent Med, Div Oral Med, Dept Restorat Sci Biomat, 801 Albany St,Suite 200, Boston, MA 02118 USA. RI Hughes, Christopher/E-1438-2014; Feres, Magda/H-7964-2012 NR 23 TC 32 Z9 36 U1 0 U2 3 PU E H ANGLE EDUCATION RESEARCH FOUNDATION, INC PI NEWTON N PA 1615 BEACON ST, NEWTON N, MA 02468-1507 USA SN 0003-3219 J9 ANGLE ORTHOD JI Angle Orthod. PD AUG PY 2002 VL 72 IS 4 BP 338 EP 343 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 580XQ UT WOS:000177262400010 PM 12169034 ER PT J AU Yu, FC Gibbon, GW Klaustermeyer, WB AF Yu, FC Gibbon, GW Klaustermeyer, WB TI Refractory atopic dermatitis treated with low dose cyclosporin SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Editorial Material ID DOUBLE-BLIND; THERAPEUTIC AGENT; CONTROLLED TRIAL; ECZEMA; ADULTS; COLONIZATION; COMPLEXES; DISEASE C1 Greater Los Angeles VA Med Ctr, Allergy & Immunol Sect, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Klaustermeyer, WB (reprint author), VA Greater Los Angeles Healthcare Syst, Allergy & Immunol Sect 111R, 11301 Wilshire Blvd,Bldg 500, Los Angeles, CA 90073 USA. NR 34 TC 1 Z9 1 U1 0 U2 1 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD AUG PY 2002 VL 89 IS 2 BP 127 EP 131 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 585VL UT WOS:000177545200006 PM 12197567 ER PT J AU Edmonds, ML Camargo, CA Pollack, CV Rowe, BH AF Edmonds, ML Camargo, CA Pollack, CV Rowe, BH TI The effectiveness of inhaled corticosteroids in the emergency department treatment of acute asthma: A meta-analysis SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Canadian-Association-of-Emergency-Physicians CY OCT, 1999 CL QUEBEC CITY, CANADA SP Canadian Assoc Emergency Physicians ID STEROIDS BECLOMETHASONE DIPROPIONATE; RANDOMIZED CONTROLLED TRIAL; ORAL PREDNISONE; BUDESONIDE; CHILDREN; EXACERBATIONS; SAFETY AB Study objective: Inhaled corticosteroids (ICSs) are of proven benefit in the treatment of chronic asthma; however, their role in the management of acute asthma is unclear. Methods: We performed a systematic review of randomized controlled trials involving children or adults treated in the emergency department for acute asthma with or without the addition of ICSs. Outcome measures included hospital admission, pulmonary function tests, and side effects. Results: Seven trials were selected for inclusion in the primary analyses. ICSs versus placebo were compared; data were not available on 1 of these trials. In the remaining 6 trials, a total of 352 patients were studied (179 ICS-treated and 173 non-ICS-treated patients). Two trials compared ICSs plus systemic corticosteroids versus placebo plus systemic corticosteroids; 4 trials compared ICSs versus placebo. Patients treated with ICSs were less likely to be admitted to the hospital (odds ratio 0.30; 95% confidence interval [CI] 0.16 to 0.57) and showed small improvements in peak expiratory flows (weighted mean difference 8%; 95% CI 3% to 13%) Overall, the treatment was well tolerated, with few reports of adverse side effects. A secondary analysis compared ICSs alone versus systemic corticosteroids alone; in the 4 included trials, significant heterogeneity between the study results for admission rates precluded meaningful pooling of admission data. Conclusion: There is evidence of decreased admission rates for patients with acute asthma treated with ICSs. However, there is insufficient evidence that ICS therapy results in clinically important changes in pulmonary function when used in acute asthma, and there is insufficient evidence that ICSs alone are as effective as systemic corticosteroids. C1 Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Capital Hlth Author, Edmonton, AB, Canada. Univ Alberta, Fac Med & Dent, Div Emergency Med, Walter Mackenzie Ctr 1G163, Edmonton, AB T6G 2B7, Canada. RP Rowe, BH (reprint author), Univ Alberta, Fac Med & Dent, Div Emergency Med, Walter Mackenzie Ctr 1G163, 8440-112th St, Edmonton, AB T6G 2B7, Canada. FU NHLBI NIH HHS [HL-03533] NR 34 TC 21 Z9 23 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2002 VL 40 IS 2 BP 145 EP 154 DI 10.1067/mem.2002.124753 PG 10 WC Emergency Medicine SC Emergency Medicine GA 579GR UT WOS:000177170700002 PM 12140492 ER PT J AU Maio, RF Garrison, HG Spaite, DW Desmond, JS Gregor, MA Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR O'Malley, PJ AF Maio, RF Garrison, HG Spaite, DW Desmond, JS Gregor, MA Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR O'Malley, PJ TI Emergency Medical Services Outcomes Project (EMSOP) IV: Pain measurement in out-of-hospital outcomes research SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID TOTAL HIP-REPLACEMENT; VISUAL ANALOG; RATING-SCALES; CLINICAL PAIN; CHILDREN; ANALGESIA; ANESTHESIA; CANCER; CARE AB The purpose of the Emergency Medical Services Outcomes Project (EMSOP) is to develop a foundation and framework for out-of-hospital outcomes research. In prior work (EMSOP 1), discomfort had the highest weighted score among outcome categories for the top 3 adult conditions (ie, minor trauma, respiratory distress, chest pain) and the first and third highest rankings for children's conditions (ie, minor trauma, respiratory distress). In this fourth article in the EMSOP series, we discuss issues relevant to the measurement of pain in the out-of-hospital setting, recommended pain measures that require evaluation, and implications for outcomes research focusing on pain. For adults, adolescents, and older children, 2 verbal pain-rating scales are recommended for out-of-hospital evaluation: (1) the Adjective Response Scale, which includes the responses "none," "slight," "moderate," 11 severe," and "agonizing," and (2) the Numeric Response Scale, which includes responses from 0 (no pain) to 100 (worst pain imaginable). The Oucher Scale, combining a visual analog scale with pictures, seems most promising for out-of-hospital use among younger children. Future research in out-of-hospital care should be conducted to determine the utility and feasibility of these measures, as well as the effectiveness of interventions for pain relief. C1 Massachusetts Dept Publ Hlth, Emergency Med Serv Children, Boston, MA USA. Massachusetts Gen Hosp, Pediat Emergency Serv, Boston, MA 02114 USA. Allina Hlth Syst, St Paul, MN USA. HealthSpan Transportat Serv, St Paul, MN USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. EMSSTAR Grp, Annapolis, MD USA. New York Med Coll, Inst Trauma & Emergency Care, Valhalla, NY 10595 USA. Univ Ottawa, Loeb Hlth Res Inst, Ottawa, ON, Canada. Univ Ottawa, Div Emergency Med, Ottawa, ON, Canada. Univ Arizona, Coll Med, Dept Emergency Med, Tucson, AZ USA. E Carolina Univ, Brody Sch Med, Dept Emergency Med, Greenville, NC USA. Univ Michigan, Dept Emergency Med, Med Ctr, Ann Arbor, MI 48109 USA. RP Maio, RF (reprint author), Univ Michigan, Dept Emergency Med, Med Ctr, 300 N Ingalls Bldg,Room 2D06, Ann Arbor, MI 48109 USA. OI Spaite, Daniel/0000-0003-2601-6476; Stiell, Ian/0000-0002-2583-6408 NR 61 TC 41 Z9 41 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2002 VL 40 IS 2 BP 172 EP 179 DI 10.1067/mem.2002.124756 PG 8 WC Emergency Medicine SC Emergency Medicine GA 579GR UT WOS:000177170700006 PM 12140496 ER PT J AU Montine, TJ Quinn, JF Milatovic, D Silbert, LC Dang, T Sanchez, S Terry, E Roberts, LJ Kaye, JA Morrow, JD AF Montine, TJ Quinn, JF Milatovic, D Silbert, LC Dang, T Sanchez, S Terry, E Roberts, LJ Kaye, JA Morrow, JD TI Peripheral F-2-isoprostanes and F-4-neuroprostanes are not increased in Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Article ID RADICAL-CATALYZED MECHANISM; LIPID-PEROXIDATION; IN-VIVO; OXIDATIVE STRESS; PLASMA; NONCYCLOOXYGENASE; NEUROPROSTANES; ISOPROSTANES; PRODUCTS; ACID AB Quantitative biomarkers of oxidative damage, such as the F-2-isoprostanes (IsoPs) and F-4-neuroprostanes (F-4-NeuroPs), may be useful in assessing progression and response to therapeutics in patients with Alzheimer's disease. F-2-IsoPs and F-4-NeuroPs are reproducibly increased in brain and cerebrospinal fluid of Alzheimer's disease patients; however, results in blood and urine have been conflicting. We tested the hypothesis that F-2-IsoPs and F-4-NeuroPs in plasma or urine quantitatively reflect oxidative damage to the central nervous system. Our results showed that urine levels of F-2-IsoPs or their major metabolite were not significantly different between 56 Alzheimer's disease patients and 34 controls. In addition, urine and cerebrospinal fluid F-2-IsoP levels in 32 Alzheimer's disease patients did not correlate. Supporting these conclusions, elevated rat cerebral F-2-IsoPs and F-4-NeuroPs after systemic exposure to kainic acid were not associated with a significant change in their plasma or urine levels. These results show that plasma and urine F-2-IsoPs and F-4-NeuroPs do not accurately reflect central nervous system levels of these biomarkers and are not reproducibly elevated in body fluids outside of central nervous system in Alzheimer's disease patients. These results should guide the organization of clinical trials now being planned for patients with Alzheimer's disease. C1 Vanderbilt Univ, Med Ctr N, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr N, Dept Pharmacol, Nashville, TN 37232 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Neurol Serv, Portland, OR USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. RP Montine, TJ (reprint author), Vanderbilt Univ, Med Ctr N, Dept Pathol, C-3321A, Nashville, TN 37232 USA. OI Silbert, Lisa/0000-0002-4525-0068; Kaye, Jeffrey/0000-0002-9971-3478 FU NCI NIH HHS [CA77839]; NIA NIH HHS [AG05144, AG08017, AG16835]; NIDDK NIH HHS [DK48831]; NIGMS NIH HHS [GM15431] NR 22 TC 110 Z9 112 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2002 VL 52 IS 2 BP 175 EP 179 DI 10.1002/ana.10272 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 578UX UT WOS:000177140000007 PM 12210787 ER PT J AU Wright, CD Graham, BB Grillo, HC Wain, JC Mathisen, DJ AF Wright, CD Graham, BB Grillo, HC Wain, JC Mathisen, DJ TI Pediatric tracheal surgery SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 28-30, 2002 CL FT LAUDERDALE, FLORIDA SP Soc Thorac Surgeons ID SUBGLOTTIC STENOSIS; CRICOTRACHEAL RESECTION; CHILDREN; EXPERIENCE; RECONSTRUCTION; TRACHEOPLASTY; MANAGEMENT AB Background. Pediatric tracheal procedures are uncommon. We reviewed our experience to clarify management and results. Methods. Retrospective single-institution review of pediatric tracheal operations, 1978 to 2001. Results. One hundred sixteen children were evaluated, mean age 10.4 years (10 days to 18 years). Tracheal pathology was postintubation stenosis (n = 72; 62%), congenital stenosis (n = 23; 20%), neoplasm (n 8; 7%), tracheomalacia (n = 7; 6%), and trauma (n 6; 5%). Twenty-nine patients had previous tracheal operations. Thirty-six patients received only a minor procedure. Eighty patients had major operations: tracheal resection (n = 46; 58%), laryngotracheal resection (n = 22; 28%), slide tracheoplasty (n = 7, 9%), and carinal resection (n = 5; 6%). The mean length of airway resected was 3.3 cm (1.5 to 6 cm), which represented 30% of the entire trachea. Twenty-eight patients (35%) had complications. These included tracheomalacia (n = 3), recurrent nerve injury (n = 3), laryngeal edema requiring intubation (n = 2), stroke (n = 1), esophageal leak (n = 1), and lobar collapse (n = 1). Nineteen patients had anastomotic failure: severe restenosis (n = 6), mild restenosis (n = 9), dehiscence (n = 2), dehiscence with tracheoesophageal fistula (n = 1), and tracheoinnominate fistula (n = 1). Two children died (2.5%). Complications were more frequent in children less than 7 years of age (p = 0.05) and after previous operations (p = 0.02). Longer fractions of tracheal resection (> 30%) were more likely to result in anastomotic failure (P = 0.0005). Sixty-four (80%) patients achieved a stable airway free of any airway appliance. All patients with neoplasms are alive. Conclusions. The principles of adult tracheal operations are directly applicable to children and usually lead to a stable, satisfactory airway. Children tolerate anastomotic tension less well than adults; resections more than 30% have a substantial failure rate. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Thorac Surg, Blake 1570, Boston, MA 02114 USA. NR 23 TC 51 Z9 58 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2002 VL 74 IS 2 BP 308 EP 313 AR PII S0003-4975(02)03613-5 DI 10.1016/S0003-4975(02)03613-5 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 581XR UT WOS:000177320600003 PM 12173805 ER PT J AU Meerkin, D Pellerin, M Aretz, HT Paiement, P Houser, SL Bonan, R AF Meerkin, D Pellerin, M Aretz, HT Paiement, P Houser, SL Bonan, R TI Transmyocardial coil implants: A novel approach to transmyocardial revascularization SO ANNALS OF THORACIC SURGERY LA English DT Article ID LASER REVASCULARIZATION; MYOCARDIAL REVASCULARIZATION; CANINE MYOCARDIUM; CHANNELS; ANGIOGENESIS; ISCHEMIA AB Background. Transmyocardial laser revascularization (TMLR) has potential benefit for patients with end-stage coronary artery disease and intractable angina not amenable to conventional revascularization techniques. Neovascularization has been proposed to occur around the laser channels. Our aim was to determine the feasibility of a novel nonlaser myocardial revascularization technique and its effect on angiogenesis in a nonischemic porcine model. Methods. In the first phase, six transmyocardial stainless steel coil implants (TMI) were deployed to the lateral wall of the left ventricle in each of 6 pigs. The animals were sacrificed at 8 and 12 weeks, with a single animal dying prematurely at 4 weeks, and the myocardium was assessed for new vessel growth. In the second phase, 8 implants were deployed in each of 12 pigs with regular fluoroscopic follow-up until sacrifice at 2 weeks to assess implant stability. Results. The deployment procedure was safe and feasible with no complications evident. A significant increase in new vessels at implant sites with 5.43 +/- 3.67, 4.97 +/- 2.44, and 3.57 +/- 2.29 seen per high power field at 12, 8, and 4 weeks, respectively, compared to 1.00 +/- 1.06 (p < 0.0001) in control myocardium. There was no evidence of implant migration in Phase 2. Conclusions. TMIs can feasibly be deployed in the nonischemic pig model with a high success rate. The presence of angiogenesis at the implant site and the maintenance of this reaction for 3 months implies that TMI may offer an alternative to TMLR while providing a platform for delivery of angiogenic factors. C1 Montreal Heart Inst, Dept Med, Montreal, PQ H1T 1C8, Canada. Montreal Heart Inst, Dept Surg, Montreal, PQ H1T 1C8, Canada. Shaare Zedek Med Ctr, Dept Med, IL-91000 Jerusalem, Israel. Shaare Zedek Med Ctr, Dept Cardiol, IL-91000 Jerusalem, Israel. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bonan, R (reprint author), Montreal Heart Inst, Dept Med, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada. NR 25 TC 1 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2002 VL 74 IS 2 BP 488 EP 492 AR PII S0003-4975(02)03732-323 DI 10.1016/S0003-4975(02)03732-3 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 581XR UT WOS:000177320600046 PM 12173833 ER PT J AU Kirkpatrick, WR Perea, S Coco, BJ Patterson, TF AF Kirkpatrick, WR Perea, S Coco, BJ Patterson, TF TI Efficacy of caspofungin alone and in combination with voriconazole in a guinea pig model of invasive aspergillosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL MK-0991 L-743,872; IN-VITRO; AMPHOTERICIN-B; ECHINOCANDIN CASPOFUNGIN; FLUCONAZOLE; ITRACONAZOLE; FUMIGATUS; CANDIDA; TERBINAFINE; SUSCEPTIBILITY AB The antifungal activity of caspofungin acetate (CAS) alone and in combination with voriconazole (VRC) was evaluated in an immunosuppressed transiently neutropenic guinea pig model of invasive aspergillosis. Guinea pigs were immunosuppressed with triamcinolone at 20 mg/kg of body weight/day subcutaneously beginning 4 days prior to lethal intravenous challenge with Aspergillus fumigatus and were made temporarily neutropenic with cyclophosphamide administered at 150 mg/kg intraperitoneally (i.p.) 1 day prior to challenge. Therapy with i.p. CAS at 1 and 2.5 mg/kg/day (with and without oral VRC at 5 mg/kg/day), oral VRC at 5 mg/kg/day, or i.p. amphotericin B (AMB) at 1.25 mg/kg/day was begun 24 h after challenge and was continued for 5 days. Mortality occurred in 12 of 12 untreated controls, whereas mortality occurred in 4 of 12 and 6 of 12 guinea pigs treated with CAS at 1 and 2.5 mg/kg/day, respectively, and in 3 of 12 guinea pigs treated with AMB. No mortality occurred among animals treated with CAS at 1 mg/kg/day plus VRC at 5 mg/kg/day, CAS at 2.5 mg/kg/day plus VRC at 5 mg/kg/day, or VRC at 5 mg/kg/day alone. Both CAS regimens increased the survival times and reduced the colony counts in tissue compared with those for the controls. Treatment with VRC and AMB significantly reduced the colony counts in the tissues of selected animals compared with those in the tissues of the controls. Treatment with VRC and AMB also resulted in reductions in colony counts in tissues compared with those in the tissues of animals treated with CAS (the difference was not statistically significant) and improved the survival times but did not sterilize tissues. Combination therapies with CAS plus VRC at either dose reduced colony counts in tissues 1,000-fold over those for the controls and were the only regimens that significantly reduced the numbers of positive cultures. The combinations of CAS plus VRC were highly effective in this model and should be further evaluated for use against invasive aspergillosis. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Kirkpatrick, WR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA. NR 29 TC 195 Z9 204 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2002 VL 46 IS 8 BP 2564 EP 2568 DI 10.1128/AAC.46.8.2564-2568.2002 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 575VG UT WOS:000176968700036 PM 12121933 ER PT J AU Finegold, SM Molitoris, D Phan, VT Vaisanen, ML Wexler, HM AF Finegold, SM Molitoris, D Phan, VT Vaisanen, ML Wexler, HM TI Activities of ABT-773 against microaerophilic and fastidious organisms SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO ACTIVITIES; ANAEROBIC-BACTERIA AB ABT-773 was tested against 317 fastidious isolates; it inhibited 99% of organisms at a concentration of 4.0 mug/ml. With ampicillin-sulbactam and levofloxacin, only 2 and 6% of these strains, respectively, were resistant at the breakpoint. With clindamycin, penicillin G, and metronidazole, 22, 26, and 58% of the strains, respectively, were resistant. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles Div, Infect Dis Sect 111 F, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, W Los Angeles Div, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90024 USA. RP Finegold, SM (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles Div, Infect Dis Sect 111 F, Los Angeles, CA 90073 USA. NR 7 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2002 VL 46 IS 8 BP 2716 EP 2719 DI 10.1128/AAC.46.8.2716-2719.2002 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 575VG UT WOS:000176968700068 PM 12121965 ER PT J AU Gerson, SL Kaplan, SL Bruss, JB Le, V Arellano, FM Hafkin, B Kuter, DJ AF Gerson, SL Kaplan, SL Bruss, JB Le, V Arellano, FM Hafkin, B Kuter, DJ TI Hematologic effects of linezolid: Summary of clinical experience SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID OXAZOLIDINONE ANTIBACTERIAL AGENTS; IN-VITRO ACTIVITIES; VANCOMYCIN; THROMBOCYTOPENIA; PENICILLINS; INFECTIONS; PNU-100766; U-100592; U-100766 AB Linezolid has been associated with reversible myelosuppression. Clinical trial data were evaluated for anemia, thrombocytopenia, and neutropenia. Thrombocytopenia and a slight increased risk for anemia were evident at greater than or equal to2 weeks of linezolid treatment. Hematologic abnormalities were consistent with mild, reversible, duration-dependent myelosuppression. Appropriate monitoring is warranted with linezolid use. C1 Case Western Reserve Univ, Div Hematol Oncol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ireland Canc Ctr, BRB 3, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Pharmacia, Kalamazoo, MI USA. Pharmacia, Peapack, NJ USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA USA. RP Gerson, SL (reprint author), Case Western Reserve Univ, Div Hematol Oncol, 10900 Euclid Ave, Cleveland, OH 44106 USA. NR 21 TC 197 Z9 213 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2002 VL 46 IS 8 BP 2723 EP 2726 DI 10.1128/AAC.46.8.2723-2726.2002 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 575VG UT WOS:000176968700070 PM 12121967 ER PT J AU Park, GH McNeil, MR Doyle, PJ AF Park, GH McNeil, MR Doyle, PJ TI Lexical access rate of closed-class elements during auditory sentence comprehension in adults with aphasia SO APHASIOLOGY LA English DT Article ID CLASS WORDS; TIME; COMPLEXITY; LANGUAGE; CONTEXT; MODEL AB Background: One hypothesis regarding the underlying impairment in agrammatic comprehension suggests that individuals with this disorder suffer from a reduction in lexical activation of closed-class words and therefore cannot appropriately construct a syntactic frame on which lexical semantic information can be applied (Friederici, 1988). Aims: Given the temporally based hypothesis, this investigation examined the effects of increased inter-word intervals (IWI) following closed-class words on auditory comprehension of various sentence types by individuals with agrammatic comprehension. It was hypothesised that providing a longer temporal window for access and processing of closed-class words would improve sentence structure comprehension. Methods & Procedures: Twelve adults with aphasia participated in an agent identification task given varying auditory sentence stimuli. Six sentence types and six IWI durations served as independent variable while accuracy and response times were measured. Outcomes & Results: Results indicated that auditory sentence comprehension performance improves when IWIs are increased. However, differences exist among individuals in response to specific IWI durations. Conclusions: Implications of delayed access rates of closed-class words in agrammatic comprehension are discussed. C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Va Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Pittsburgh, Passavant Hosp, Pittsburgh, PA 15260 USA. RP Park, GH (reprint author), NIDCD, NIH, Language Sect, Bldg 10,Room 3C-716, Bethesda, MD 20892 USA. NR 40 TC 3 Z9 3 U1 1 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD AUG PY 2002 VL 16 IS 8 BP 801 EP 814 DI 10.1080/02687030244000158 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 581LQ UT WOS:000177294200003 ER PT J AU McNeil, MR Doyle, PJ Park, GH Fossett, TRD Brodsky, MB AF McNeil, MR Doyle, PJ Park, GH Fossett, TRD Brodsky, MB TI Increasing the sensitivity of the Story Retell Procedure for the discrimination of normal elderly subjects from persons with aphasia SO APHASIOLOGY LA English DT Article ID CONNECTED SPEECH; MEMORY; ADULTS; INFORMATION AB Background: Clinicians have long recognised the need for assessing language production at multiple levels of complexity and at impairment, participation, and activity levels. Methods for the elicitation of connected spoken language have taken many forms, typically selected with a balance between validly sampling linguistic performance, and reliability and economy of the sampling and scoring procedures. A Story Retell Procedure (SRP) has been proposed as a preferred method for achieving valid, reliable, and economic assessment of connected language (Doyle et al., 2000), and an information unit (IU) metric has been developed for validly and economically capturing important linguistic aspects of the retelling (McNeil, Doyle, Fossett, Park & Goda, 2001). Aims: In keeping with the goal of making assessment procedures as efficient and economic as possible, a study was undertaken to investigate the refinement of the IU metric for increasing the sensitivity of the SRP as an instrument for the detection of connected paragraph-level language production deficits in persons with aphasia. This metric involved the calculation of the percentage of lUs (%IU) produced relative to the time taken to produce them (%IU/Min). Methods & Procedures: A total of 15 persons with aphasia, and 31 normal control individuals without a communication disorder served as participants for this study. Subjects heard, and immediately retold each of 12 stories originally taken from the Discourse Comprehension Test (Brookshire & Nicholas, 1997). The retellings were scored using the procedures outlined by McNeil et al. (2001) with the addition of the %IU calculated over the time of the retelling. Comparisons between subject groups and groups stratified by age, among SRP forms, between scoring methods (%IU vs %IU/Min.), and group misclassification by scoring method were made. Outcome & Results: Application of the %IU/Min with the SRP yielded equivalence among alternate forms as evidenced by non-significant differences and high correlation coefficients among the SRP forms for persons with aphasia. The %IU/Min also decreased the percentage of misclassified aphasic and normal individuals compared to the %IU measure. Older normal subjects were misclassified as aphasic with greater frequency compared to the younger normal subjects. Conclusions: The %IU/Min is a more sensitive metric than the %IU in differentiating individuals with aphasia from older normal controls. C1 Univ Pittsburgh, Passavants Hosp, Pittsburgh, PA 15260 USA. Va Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP McNeil, MR (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorder, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. NR 24 TC 9 Z9 9 U1 1 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD AUG PY 2002 VL 16 IS 8 BP 815 EP 822 DI 10.1080/02687030244000284 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 581LQ UT WOS:000177294200004 ER PT J AU Pfefer, TJ Schomacker, KT Ediger, MN Nishioka, NS AF Pfefer, TJ Schomacker, KT Ediger, MN Nishioka, NS TI Multiple-fiber probe design for fluorescence spectroscopy in tissue SO APPLIED OPTICS LA English DT Article ID LASER-INDUCED FLUORESCENCE; HUMAN COLON TISSUE; TURBID MEDIA; IN-VIVO; OPTICAL-PROPERTIES; AUTOFLUORESCENCE; DEPTH; MODEL; LIGHT; PROPAGATION AB The fiber-optic probe is an essential component of many quantitative fluorescence spectroscopy systems, enabling delivery of excitation light and collection of remitted fluorescence in a wide variety of clinical and laboratory situations. However, there is little information available on the role of illumination-collection geometry to guide the design of these components. Therefore we used a Monte Carlo model to investigate the effect of multifiber probe design parameters-numerical aperture, fiber diameter, source-collection fiber separation distance, and fiber-tissue spacer thickness-on light propagation and the origin of detected fluorescence. An excitation wavelength of 400 ran and an emission wavelength of 630 nm were simulated. Noteworthy effects included an increase in axial selectivity with decreasing fiber size and a transition with increasing fiber-tissue spacer size from a subsurface peak in fluorophore sensitivity to a nearly monotonic decrease typical of single-fiber probes. We provide theoretical evidence that probe design strongly affects tissue interrogation. Therefore application-specific customization of probe design may lead to improvements in the efficacy of fluorescence-based diagnostic devices. (C) 2002 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Radiol Hlth, FDS CDRH HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. EM josh@eob.cdrh.fda.gov RI Pfefer, Josh/I-9055-2012 NR 36 TC 70 Z9 70 U1 1 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD AUG 1 PY 2002 VL 41 IS 22 BP 4712 EP 4721 DI 10.1364/AO.41.004712 PG 10 WC Optics SC Optics GA 579NY UT WOS:000177185800040 PM 12153108 ER PT J AU Yun, PL Arndt, KA Anderson, RR AF Yun, PL Arndt, KA Anderson, RR TI Q-Switched laser-induced chrysiasis treated with long-pulsed laser SO ARCHIVES OF DERMATOLOGY LA English DT Article ID GOLD; EXPOSURE; THERAPY C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Skin Care Phys Chestnut Hill, Chestnut Hill, MA USA. RP Anderson, RR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St,BHX-630, Boston, MA 02114 USA. NR 14 TC 12 Z9 12 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 AUG PY 2002 VL 138 IS 8 BP 1012 EP 1014 DI 10.1001/archderm.138.8.1012 PG 3 WC Dermatology SC Dermatology GA 584ZR UT WOS:000177499100001 PM 12164737 ER PT J AU Brkanac, Z Bylenok, L Fernandez, M Matsushita, M Lipe, H Wolff, J Nochlin, D Raskind, WH Bird, TD AF Brkanac, Z Bylenok, L Fernandez, M Matsushita, M Lipe, H Wolff, J Nochlin, D Raskind, WH Bird, TD TI A new dominant spinocerebellar ataxia linked to chromosome 19q13.4-qter SO ARCHIVES OF NEUROLOGY LA English DT Article ID CEREBELLAR-ATAXIA; LINKAGE ANALYSIS; FAMILIES; CHANNEL; MAPS AB Background: The autosomal dominant spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders. Although molecular genetic studies have so far implicated 16 loci in the etiology of these diseases, approximately 30% of families with SCAs remain unlinked. Objectives: To report the location of a gene causing a "pure" autosomal dominant cerebellar ataxia in one family and to describe the clinical phenotype. Patients: We have identified a 4-generation American family of English and Dutch ethnicity with a pure cerebellar ataxia displaying an autosomal dominant pattern of inheritance. The disease typically has its onset in the third and fourth decades of life, shows no evidence of anticipation, progresses slowly, and does not appear to decrease life expectancy. Clinical DNA testing excluded SCA1, 2, 3, 6, 7, and 8. Methods: A genome-wide linkage analysis at a 10 centimorgan (cM) level was performed with samples from 26 family members (11 affected, 10 clinically unaffected at risk, and 5 spouses) Results: Assuming 90% penetrance, we found suggestive evidence of linkage to chromosome 19, with a lod score of 2.49 for D19S571. More detailed mapping in this region provided a maximum 2-point led score of 2.57 at theta = 0 for D19S254 and a maximum multipoint lod score of 4.72 at D19S926. By haplotype construction a 22-cM critical region from D19S601 to the q telomere was defined. Conclusions: We have mapped a gene for an autosomal dominant SCA to chromosome 19q13.4-qter in one family. The critical region overlaps with the locus for SCA14, a disease described in a single Japanese family and characterized by axial myoclonus. Myoclonus was not seen in the family we studied, but it remains possible that the 2 disorders are allelic variants. C1 Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Ohio State Univ, Dept Med, Columbus, OH 43210 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA USA. RP Raskind, WH (reprint author), Univ Washington, Sch Med, Dept Med, Box 35-7720, Seattle, WA 98195 USA. NR 17 TC 30 Z9 32 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2002 VL 59 IS 8 BP 1291 EP 1295 DI 10.1001/archneur.59.8.1291 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 583DQ UT WOS:000177391000010 PM 12164726 ER PT J AU Brickman, AM Riba, A Bell, K Marder, K Albert, M Brandt, J Stern, Y AF Brickman, AM Riba, A Bell, K Marder, K Albert, M Brandt, J Stern, Y TI Longitudinal assessment of patient dependence in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID ACTIVITY SURVEY CAS; ALPHA-TOCOPHEROL; CONTROLLED TRIAL; CLINICAL-TRIALS; DEMENTIA; MULTICENTER; PREDICTORS; CAREGIVER; PARTICIPATION; VALIDATION AB Background: The Dependence Scale measures the amount of assistance patients with dementia require in performing daily activities. Validity and reliability of this scale have been demonstrated, but the progression throughout long periods in patients with Alzheimer disease (AD) has not previously been examined. Objective: To determine the longitudinal course of patient dependence in a cohort of prospectively followed AD patients. Methods: Two hundred thirty AD patients enrolled in the Predictors Study were followed up prospectively at 6-month intervals for an average of 6.5 visits. The Dependence Scale was administered to a caregiver, and patients were assessed with the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale. Dependence level and the additive sum of the Dependence Scale items were considered for analysis. Results: Generalized estimating equations to regression analyses were used to determine that both Dependence Scale scores and dependence level significantly decline with time. By covarying mMMSE scores and self-care deficits factor scores of the Blessed Dementia Rating Scale, generalized estimating equations analysis also demonstrated that change in patient dependence was independent of global cognitive decline and other measures of activities of daily living, respectively. Conclusions: This study shows the validity of the Dependence Scale and demonstrated that dependency in AD significantly declines with time independent of global cognition and other self-care deficits. The scale is a valuable instrument for outcomes research, efficacy trials, and behavioral research in AD. C1 Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Taub Alzheimers Dis Res Ctr, New York, NY 10032 USA. CUNY Queens Coll, Dept Psychol, New York, NY USA. CUNY, Grad Ctr, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Alzheimers Dis Res Ctr, Baltimore, MD 21205 USA. RP Stern, Y (reprint author), Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, 630 W 168th St, New York, NY 10032 USA. OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR 00645]; NIA NIH HHS [AG 07370] NR 31 TC 35 Z9 36 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2002 VL 59 IS 8 BP 1304 EP 1308 DI 10.1001/archneur.59.8.1304 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 583DQ UT WOS:000177391000012 PM 12164728 ER PT J AU Fisher, CM AF Fisher, CM TI Unexplained sudden amnesia SO ARCHIVES OF NEUROLOGY LA English DT Article AB Background: In almost all cases of acute, sudden, persistent amnesia, the cause can be determined. Ischemic stroke, hypoglycemia, syncope, and seizure are the most likely causes. Patients and Methods: In a clinical study, 2 elderly men are described in which sudden, permanent amnesia developed in the absence of a satisfactory explanation. In I case, a neuropathologic study disclosed Alzheimer disease; in the other, magnetic resonance imaging showed a temporal lobe abnormality bilaterally. Results: A man aged 80 years suddenly lost his memory of the previous 60 years. Neuropathologic study 5 years later showed the changes of Alzheimer disease. in the second case a disabling amnesia developed overnight in a man aged 70 years. There was no progression of the disabling amnesia in the next 15 years. Magnetic resonance imaging 10 years from the onset showed abnormality of the medial temporal lobe bilaterally. Conclusions: In neither case was the amnesia satisfactorily explained. It is likely that rare cases of amnesia occur as the result of an unrecognized pathophysiologic process. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, VBK 910,55 Fruit St, Boston, MA 02114 USA. NR 1 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2002 VL 59 IS 8 BP 1310 EP 1313 DI 10.1001/archneur.59.8.1310 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 583DQ UT WOS:000177391000013 PM 12164729 ER PT J AU Ambati, BK Joussen, AM Ambati, J Moromizato, Y Guha, C Javaherian, K Gillies, S O'Reilly, MS Adamis, AP AF Ambati, BK Joussen, AM Ambati, J Moromizato, Y Guha, C Javaherian, K Gillies, S O'Reilly, MS Adamis, AP TI Angiostatin inhibits and regresses corneal neovascularization SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LEWIS-LUNG-CARCINOMA; LASER PHOTOCOAGULATION; PHOTODYNAMIC THERAPY; GENE-TRANSFER; ANGIOGENESIS; RAT; PLASMINOGEN; MODEL; METALLOELASTASE; THALIDOMIDE AB Objective: To determine the ability of angiostatin and the angiostatin-producing low-metastatic (LM) clone of Lewis lung carcinoma (LLC) to inhibit and regress corneal neovascularization, as compared with the nonangiostatin-producing high-metastatic (HM) clone. Methods: Three groups of C57BL6/J mice underwent chemical and mechanical denudation of corneal and limbal epithelium. One group remained tumor free while the other 2 were implanted with LLC cells (either the HM or LM clones) subcutaneously the day before, 2 weeks after, or 4 weeks after denudation. Corneas were harvested 2 weeks after tumor implantation (at 2, 4, and 6 weeks after denudation for tumor-free mice). Neovascularization was quantified by CD31 immunostaining. In a second experiment, recombinant angiostatin was delivered continuously for 2 weeks via an osmotic pump in mice with established corneal neovascularization. Results: The mean percentages of neovascularized corneal area in mice 2 weeks after LM-LLC implantation were 4.6%, 3.7%, and 37.0%, at 2, 4, and 6 weeks after scraping, respectively. In contrast, in the mice implanted with HM-LLC, the corresponding values were 45.4% (P =.01), 90.1% (P=.03), and 80.3% (P=.005). For tumor-free mice, the corresponding values were 62.0% (P=.003), 68.9% (P=.03), and 59.3% (P=.06). Mice implanted with angiostatin pumps had a 37.7% neovascularized corneal area 2 weeks after implantation and 4 weeks after scraping while mice implanted with sham pumps had 60.5% (P=.007). Conclusion: Angiostatin inhibits and regresses corneal neovascularization induced by mechanical and alkali corneal injury. Clinical Relevance: This appears to be the first evidence of biologically induced regression of corneal neovascularization, and the first direct demonstration of angiostatin-induced regression of neovascularization in any tissue. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiat Oncol, Bronx, NY 10467 USA. Lexigen Pharmaceut, Lexington, MA USA. Univ Texas, MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 34 TC 54 Z9 59 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2002 VL 120 IS 8 BP 1063 EP 1068 PG 6 WC Ophthalmology SC Ophthalmology GA 582JF UT WOS:000177346500006 PM 12149060 ER PT J AU Niederman, R Kelderman, H Socransky, S Ostroff, G Genco, C Kent, R Stashenko, P AF Niederman, R Kelderman, H Socransky, S Ostroff, G Genco, C Kent, R Stashenko, P TI Enhanced neutrophil emigration and Porphyromonas gingivalis reduction following PGG-glucan treatment of mice SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE neutrophils; immunomodulation; bacterial infection; P. gingivalis ID BACTEROIDES-GINGIVALIS; HOST RESPONSE; PERIODONTITIS; RESISTANCE; INFECTION AB Periodontal disease is the consequence of a mixed Gram-negative infection in the gingival sulcus and has been associated with deficits in the neutrophil response. A novel, and heretofore untested, alternative approach to therapy is the use of biological-response modulators that enhance the neutrophil response. Poly-beta1-6-glucotriosyl-beta1-3-glucopyranose glucan (PGG-glucan) is an immunomodulator, derived from yeast, which specifically enhances neutrophil priming, phagocytosis and bacterial killing while failing to induce inflammatory cytokine expression. The hypothesis tested was that PGG-glucan could enhance host resistance to a Gram-negative periodontal pathogen, Porphyromonas gingivalis. Chambers were implanted subcutaneously in the dorsolumbar region of C57BL/6J mice and allowed to heal for 14 days. PGG-glucan was administered subcutaneously to one-half of the animals and saline to the other half. In the first set of experiments the chambers were inoculated with P. gingivalis (A7436) at 4 x 10(6), 4 x 10(7), and 4 x 10(8) colony-forming units (CFU). In the second set of experiments the chambers were inoculated with 5 x 10(8) CFU of either P. gingivalis or Streptococcus sanguis, a Gram-positive oral microbe that is not periodontopathic. Chambers were sampled over the following 2 weeks. The results demonstrated that: (1) bacterial CFU and neutrophils increased with increasing bacterial inoculum (P < 0.02); (2) bacterial CFU were lower in the PGG-glucan-treated animals than in the saline controls (P < 0.02); and (3) neutrophil Counts were higher in the PGG-glucan-treated animals than in the saline controls (P < 0.01). These results indicate that PGG-glucan significantly enhances neutrophil emigration and bacterial killing, thus decreasing the bacterial infection in this model system. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Biopolymer Engn Inc, Eagan, MN 55121 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Stashenko, P (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. OI niederman, richard/0000-0001-6674-1774 FU NIDCR NIH HHS [DE-11664, DE-13747] NR 20 TC 8 Z9 8 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD AUG PY 2002 VL 47 IS 8 BP 613 EP 618 AR PII S0003-9969(02)00042-0 DI 10.1016/S0003-9969(02)00042-0 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 603KL UT WOS:000178558400008 PM 12221019 ER PT J AU Hartnick, CJ AF Hartnick, CJ TI Validation of a pediatric voice quality-of-life instrument - The pediatric voice outcome survey SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Pediatric-Otolaryngology CY MAY 13-14, 2002 CL BOCA RATON, FLORIDA SP Amer Soc Pediatr Otolarygol ID HEALTH-STATUS; CHILDREN; ADOLESCENCE; PARALYSIS; ILLNESS AB Objective: To validate a parent proxy instrument to study the voice-related quality of life (VR-QOL) for the pediatric population. Methods: The voice outcome survey (VOS) was administered to 108 caregivers of children aged 2 to 18 years, who either had a tracheotomy or had achieved surgical decannulation. The VOS was altered so that each item was addressed to the parent proxy as opposed to the child. A scoring paradigm was developed to report the scores on a range of 0 to 100. Structural properties of the instrument examined include validity, reliability, and principal component analysis. The VOS was then revised to suit the results of this analysis. Results: The mean +/- SD (range) score for the pediatric VOS was 49.8 +/- 27.1 (0-100). Reliability analysis and principal component analysis supported the reduction of 1 item from the final pediatric VOS. The revised instrument demonstrated an overall Cronbach alpha value of .86. Substratification by age revealed robust Cronbach alpha values from ages 2 to 18 years. Construct validity analysis also supported statistical significance (P=.004). Principal component analysis of the revised instrument supports its internal structure and design. Conclusions: The pediatric VOS is a simple, short, health status instrument designed to measure the VR-QOL in the pediatric population. Cross-sectional analysis suggests that children and adolescents with tracheotomies have a poorer VR-QCL than do those who have achieved decannulation. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 64 Z9 66 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2002 VL 128 IS 8 BP 919 EP 922 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 582JD UT WOS:000177346300009 PM 12162771 ER PT J AU Novis, DA Friedberg, RC Renner, SW Meier, FA Walsh, MK AF Novis, DA Friedberg, RC Renner, SW Meier, FA Walsh, MK TI Operating room blood delivery turnaround time - A College of American Pathologists Q-Probes study of 12 647 units of blood components in 466 institutions SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SMALL HOSPITALS; LABORATORIES; TIMELINESS; EMERGENCY; PERFORMANCE; BIOPSIES AB Objectives.-To determine the normative distribution of time elapsed for blood bank personnel to fill nonscheduled operating room (OR) blood component orders in hospital communities throughout the United States, and to examine hospital blood bank practices associated with faster blood component delivery times. Design-Participants in the College of American Pathologists Q-Probes laboratory quality improvement program collected data prospectively on the times elapsed for blood bank personnel to fill nonscheduled emergent orders from hospital ORs for red blood cell (RBC) products, fresh frozen plasma (FFP), and platelets (PLTs). Participants also completed questionnaires describing their hospitals' and blood banks' laboratory and transfusion practices. Setting and Participants.-Four hundred sixty-six public and private institutions located in 48 states in the United States (n = 444), Canada (n = 9), Australia (n = 8), the United Kingdom (n = 4), and Spain (n = 1). Main Outcome Measures.-The median time elapsed between requests for blood components by OR personnel and the retrieval of those components by blood component transport personnel, and the median time elapsed between requests for blood components by OR personnel and the arrival of those components in ORs. Results.-Participants submitted data on 12 647 units of RBCs, FFP, and PLTs. The median aggregate request-to-retrieval turnaround times (TATs) for RBCs, FFP, and PLTs ranged from 30 to 35 minutes, and the median aggregate request-to-arrival TATs for RBCs, FFP, and PLTs ranged from 33 to 39 minutes. Most of the TAT was consumed by events occurring prior to, rather than after release of components from blood banks. Shorter prerelease TATs were associated with having surgical schedules that listed patients' names and procedures available to blood bank personnel prior to surgeries, and having adequate clotted specimens in the blood bank and completed type-and-screen procedures performed before requests for blood components were submitted to blood banks. Among the fastest-performing 10% of participants (90th percentile and above), request-to-retrieval TATs ranged from 12 to 24 minutes for the 3 blood components, whereas among the slowest-performing 10% of participants (loth percentile and below), request-to-retrieval TATs ranged from 63 to 115 minutes for the 3 components. Median TATs ranged from 33 to 37 minutes for the 3 components. Institutions with TATs in the fastest-performing 25th percentile more frequently stored cross-matched RBCs in the OR daily, stocked PLTs for unexpected surgical use, stored PLTs in or near the OR, and had laboratory rather than nonlaboratory personnel deliver components to the OR than did those institutions with TATs in the slowest-performing 25th percentile. Conclusions.-Hospital blood bank personnel can deliver blood components to the OR in slightly longer than 30 minutes, measured from the time that those units are requested by OR personnel. Practices aimed at saving time before components are released from blood banks will be more efficient in reducing overall TAT than those practices aimed at saving time after components are released from blood banks. Specific practices associated with shorter blood delivery TATs included providing blood bank personnel with access to the names of surgical patients potentially requiring blood components, having pretransfusion testing completed on those patients prior to surgery, having ample blood products on hand, and having laboratory personnel control blood product delivery. C1 Wentworth Douglass Hosp, Dept Pathol, Dover, NH 03820 USA. Baystate Med Ctr, Dept Pathol, Springfield, MA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Alfred I DuPont Hosp Children, Dept Pathol, Wilmington, DE USA. Coll Amer Pathologists, Northfield, IL USA. RP Novis, DA (reprint author), Wentworth Douglass Hosp, Dept Pathol, Dover, NH 03820 USA. NR 20 TC 15 Z9 17 U1 0 U2 2 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 AUG PY 2002 VL 126 IS 8 BP 909 EP 914 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 585AE UT WOS:000177500300003 PM 12171488 ER PT J AU Imai, Y Mark, EJ AF Imai, Y Mark, EJ TI Cystic adenomatoid change is common to various forms of cystic lung diseases of children - A clinicopathologic analysis of 10 cases with emphasis on tracing the bronchial tree SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INTRALOBAR PULMONARY SEQUESTRATION; BRONCHOPULMONARY FOREGUT MALFORMATIONS; CONGENITAL-MALFORMATIONS; ATRESIA; LESIONS; SPECTRUM AB Context.-Congenital cystic adenomatoid malformation, intralobar sequestration, extralobar sequestration, bronchopulmonary foregut malformation, bronchial atresia, and lobar emphysema generally are treated as separate entities, but there are commonalities among them. Objective.-To clarify the identity of congenital cystic adenomatoid malformation in relation to other cystic diseases Design.-We studied 10 consecutive cases of surgically resected cystic lung disease in children. We studied the bronchial and vascular trees by mapping bronchi, pulmonary blood vessels, systemic blood vessels, the size and configuration of cysts, and associated scarring. Results.-The cystic lesions proved to be the following: 1 case of congenital cystic adenomatoid malformation, 2 cases of bronchial atresia With congenital cystic adenomatoid malformation, 1 hybrid case of congenital cystic adenomatoid malformation and intralobar sequestration, 1 case of intralobar sequestration with an aberrant hilum, 3 cases of intralobar sequestration with bronchial obliteration, 1 case of lung abscess, and 1 case of lobar emphysema. Congenital cystic adenomatoid malformation was the sole pathologic diagnosis in 1 case, but 7 other specimens had cystic adenomatoid change to various degrees. There was no bronchial connection between the cystic lesions and the patient's airway in 8 cases. The bronchial tree was absent in the cystic lung in 2 cases. Bronchus tapered into scar near the cystic lesion in 4 cases. Only 1 case had no significant bronchial abnormality. Conclusion.-The high incidence of cystic adenomatoid change in cystic lung disease associated with an abnormality of the bronchial tree suggests that cystic adenomatoid change may develop together with and be related to other congenital or acquired conditions in the lung. C1 Kobe City Gen Hosp, Chuo Ku, Kobe, Hyogo 6500046, Japan. Kobe Childrens Hosp Hyogo Prefecture, Kobe, Hyogo, Japan. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Int Ctr Diagnost Pathol, Kobe Operat Ctr, Kobe, Hyogo, Japan. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Imai, Y (reprint author), Kobe City Gen Hosp, Chuo Ku, 4-6 Minatojimanakamachi, Kobe, Hyogo 6500046, Japan. NR 57 TC 20 Z9 23 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 2002 VL 126 IS 8 BP 934 EP 940 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 585AE UT WOS:000177500300006 PM 12171491 ER PT J AU Thomson, CC Roberts, K Curran, A Ryan, L Wright, RJ AF Thomson, CC Roberts, K Curran, A Ryan, L Wright, RJ TI Caretaker-child concordance for child's exposure to violence in a preadolescent inner-city population SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID COMMUNITY VIOLENCE; BEHAVIOR PROBLEMS; NATIONAL SURVEY; SUBSTANCE USE; RISK-FACTORS; YOUTH; VICTIMIZATION; ADOLESCENTS; SAMPLE; WITNESSES AB Background: Effective screening for exposure to violence (ETV) in the pediatric setting depends on informant reliability and recognition of patients at increased risk. Pediatricians screening for children's ETV often rely on parent reporting. Hypothesis: That there would be poor caretaker-child concordance given that children would report events occurring outside the home not witnessed by the caretaker and that ETV would be higher among immigrant families. Objectives: To examine concordance between caretaker and child self-report of the child's ETV in a preadolescent population and to explore factors related to increased risk. Design: Community-based survey. Setting: Urban community health center. Participants: One hundred sixty-five caretaker-child pairs. Methods: The ETV was assessed by means of a standardized interview questionnaire on location and frequency of ETV. A Rasch model was used to develop summary scores of ETV (frequency and severity). Results: Caretaker-child concordance on reports of child's ETV was poor. The K statistics ranged from-0.04 for seeing someone knifed to 0.39 for witnessing a shooting. Children reported ETV more often in their neighborhood or at school, whereas caretakers reported more events near or at home. Univariate predictors of child's self-reported ETV were female sex (beta +/- SE, -10.1 +/- 4.6; P=.03) and caretaker being divorced (beta +/- SE, 12.6 +/- 6.0; P=.04). In multivariate analyses, country of origin predicted child's ETV, adjusting for child's age and sex, and caretaker educational status and marital status. Conclusions: Caretakers and their children have poor agreement on reports of the child's ETV. Intervention strategies around ETV should include assessment of the child independent of caretaker report for preadolescents. Screening may be more effective if pediatricians are aware of factors related to increased risk, including immigration status and caretaker marital status. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care, Boston, MA 02215 USA. RP Wright, RJ (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NHLBI NIH HHS [HL07427, HL07427-22]; NIGMS NIH HHS [GM553353] NR 41 TC 35 Z9 36 U1 0 U2 2 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 AUG PY 2002 VL 156 IS 8 BP 818 EP 823 PG 6 WC Pediatrics SC Pediatrics GA 581GV UT WOS:000177284100016 PM 12144374 ER PT J AU Hlatky, L Sachs, RK Vazquez, M Cornforth, MN AF Hlatky, L Sachs, RK Vazquez, M Cornforth, MN TI Radiation-induced chromosome aberrations: insights gained from biophysical modeling SO BIOESSAYS LA English DT Review ID IN-SITU HYBRIDIZATION; DOUBLE-STRAND BREAKS; INDUCED STRUCTURAL-ABERRATIONS; PERIPHERAL-BLOOD LYMPHOCYTES; EXCHANGE ABERRATIONS; INTERPHASE CHROMOSOMES; IONIZING-RADIATION; MAMMALIAN-CELLS; INTERACTION-DISTANCE; TRACK STRUCTURE AB Enzymatic misrepair of ionizing-radiation-induced DNA damage can produce large-scale rearrangements of the genome, such as translocations and dicentrics. These and other chromosome exchange aberrations can cause major phenotypic alterations, including cell death, mutation and neoplasia. Exchange formation requires that two (or more) genomic loci come together spatially. Consequently, the surprisingly rich aberration spectra uncovered by recently developed techniques, when combined with biophysically based computer modeling, help characterize large-scale chromatin architecture in the interphase nucleus. Most results are consistent with a picture whereby chromosomes are mainly confined to territories, chromatin motion is limited, and interchromosomal interactions involve mainly territory surfaces. Aberration spectra and modeling also help characterize DNA repair/ misrepair mechanisms. Quantitative results for mammalian cells are best described by a breakage-and-reunion model, suggesting that the dominant recombinational mechanism during the G(0)/G(1) phase of the cell cycle is non-homologous end-joining of radiogenic DNA double strand breaks. In turn, better mechanistic and quantitative understanding of aberration formation gives new insights into health-related applications. (C) 2002 Wiley Periodicals, Inc. C1 Univ Calif Berkeley, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Sachs, RK (reprint author), Univ Calif Berkeley, 918 Evans Hall,MC 3840, Berkeley, CA 94720 USA. NR 85 TC 57 Z9 60 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD AUG PY 2002 VL 24 IS 8 BP 714 EP 723 DI 10.1002/bies.10126 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 577ZG UT WOS:000177092500007 PM 12210532 ER PT J AU Whyte, EM Mulsant, BH AF Whyte, EM Mulsant, BH TI Post stroke depression: Epidemiology, pathophysiology, and biological treatment SO BIOLOGICAL PSYCHIATRY LA English DT Review DE stroke; depression; prevalence; etiology; treatment; review ID POSTSTROKE MOOD DISORDERS; GENERALIZED ANXIETY DISORDER; SILENT CEREBRAL INFARCTION; LATE-LIFE DEPRESSION; DOUBLE-BLIND TRIAL; MAJOR DEPRESSION; RISK-FACTORS; FOLLOW-UP; CEREBROVASCULAR LESIONS; ELECTROCONVULSIVE-THERAPY AB Depression is a common occurrence after stroke and is associated with excess disability, cognitive impairment, and mortality. The authors undertook a systematic review of the English language literature to review several aspects of this illness, including the prevalence of this disorder, the debate on its etiology, and the current understanding of the biological treatment of poststroke depression. Methodological problems encountered in the study of poststroke depression are highlighted throughout the manuscript. The authors conclude that the available evidence supports poststroke depression as being multifactorial in origin and consistent with the biopsychosocial model of mental illness. (C) 2002 Society of Biological Psychiatry. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15213 USA. Pittsburgh VA Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Mulsant, BH (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, VA Pittsburgh Hlth Care Syst, 3811 O Hara St,TDH,WPID,Room E-837, Pittsburgh, PA 15213 USA. RI crona, malin/B-7085-2012 FU NIMH NIH HHS [MH01613, T32 MH19986] NR 122 TC 218 Z9 252 U1 10 U2 41 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 AUG 1 PY 2002 VL 52 IS 3 BP 253 EP 264 AR PII S0006-3223(02)01424-5 DI 10.1016/S0006-3223(02)01424-5 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 584TG UT WOS:000177484400013 PM 12182931 ER PT J AU Kay, JH Altshuler, LL Ventura, J Mintz, J AF Kay, JH Altshuler, LL Ventura, J Mintz, J TI Impact of axis II comorbidity on the course of bipolar illness in men: a retrospective chart review SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; illness course; personality disorder ID PERSONALITY-DISORDERS; DEPRESSION AB Objectives: The purpose of this study was to investigate whether the presence of comorbid personality disorder influences the course of bipolar illness. Methods: Fifty-two euthymic male bipolar I out-patients were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID II). Bipolar patients with an axis II diagnosis were compared with those without an axis II diagnosis on retrospectively obtained demographic, clinical and course of illness variables. Results: Thirty-eight percent of the bipolar patients met criteria for an axis II diagnosis. Two (4%) met criteria for (only) a Cluster A disorder, four (8%) for (only) a Cluster B, and six (12%) for (only) a Cluster C disorder. One (2%) bipolar patient met criteria a disorder in both Clusters A and B, and one (2%) for a disorder in Clusters B and C. Five (10%) met criteria for at least one disorder in Clusters A and C, and one met criteria for disorders in Clusters A, B, and C. The presence of a personality disorder was significantly associated with a lower rate of current employment, a higher number of currently prescribed psychiatric medications, and a higher incidence of a history of both alcohol and substance use disorders compared with the bipolar patients without axis II pathology. Conclusions: Our results extend previous findings of an association between comorbid personality disorder in bipolar I patients and factors that suggest a more difficult course of bipolar illness. C1 Greater Los Angeles VA Healthcare Syst, W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat, Los Angeles, CA USA. RP Altshuler, LL (reprint author), 300 Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. NR 21 TC 37 Z9 37 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2002 VL 4 IS 4 BP 237 EP 242 DI 10.1034/j.1399-5618.2002.01165.x PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 571JK UT WOS:000176714100003 PM 12190712 ER PT J AU Polgar, J Chung, SH Reed, GL AF Polgar, J Chung, SH Reed, GL TI Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion SO BLOOD LA English DT Article ID MOLECULAR MECHANISMS; EXOCYTOSIS; SYNTAXIN-4; FUSION; ACTIVATION; SNAP-23; IDENTIFICATION; HOMOLOG; RELEASE AB Secretion of platelet granules is necessary for normal hemostasis. Platelet secretion requires soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) complex formation between different members of the syntaxin, SNAP-25, and vesicle-associated membrane protein (VAMP) gene families. Using microcapillary reverse-phase high-performance liquid chromatography-nano-electrospray tandem mass spectrometry, we identified VAMP-3 and VAMP-8 as VAMP isoforms coimmunoprecipitated from platelets with syntaxin 4. Immunoblotting experiments confirmed the presence of VAMP-3 and VAMP-8 but not VAMP-1 or VAMP-2 in platelets. To examine the effect of VAMP proteins on platelet secretion, soluble recombinant (r) VAMP-2, rVAMP-3, and rVAMP-8 Were incubated with streptolysin O-permeabilized platelets. Secretion of a granules (monitored by flow cytometric measurement of P-selectin) was blocked, and dense-granule secretion (assessed by,release of carbon 14-serotonin) was almost completely inhibited by rVAMP-3 whereas rVAMP-8 inhibited secretion of dense granules but not alpha granules. In contrast, rVAMP-2, which formed SNARE complexes in vitro, had no effect on platelet exocytosis. We conclude that VAMP-3 and VAMP-8 form SNARE complexes with platelet syntaxin 4 and are required for platelet granule secretion. (C) 2002 by The American Society of Hematology. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 665 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-64057] NR 17 TC 105 Z9 110 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 AUG 1 PY 2002 VL 100 IS 3 BP 1081 EP 1083 DI 10.1182/blood.V100.3.1081 PG 3 WC Hematology SC Hematology GA 578LA UT WOS:000177118000050 PM 12130530 ER PT J AU Chiarugi, A Pitari, GM Costa, R Ferrante, M Villari, L Amico-Roxas, M Godfraind, T Bianchi, A Salomone, S AF Chiarugi, A Pitari, GM Costa, R Ferrante, M Villari, L Amico-Roxas, M Godfraind, T Bianchi, A Salomone, S TI Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE copper; endothelium; nitric oxide; superoxide; eNOS; PECAM-1; tiron ID LOW-DENSITY-LIPOPROTEIN; NITRIC-OXIDE SYNTHASE; SUPEROXIDE-DISMUTASE; CORONARY-ARTERIES; CELLS; CERULOPLASMIN; INHIBITION; CHAPERONE; ION; MECHANISM AB 1 We investigated the effects of prolonged exposure to copper (Cu2+) on vascular functioning of isolated rat aorta. 2 Aortic rings were exposed to CuSO4 (3-24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence Of Cu2+. 3 Exposure to 2 pm Cu2+ in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 muM PE by 30% (P<0.05) and impaired the relaxant response to 3 muM ACh or 1 muM A23187 (ACh, from 65.7 +/- 7.1 to 6.2 +/- 1.1%, n = 8; A23187, from 74.6 +/- 8.2 to 12.0 +/- 0.8%, n = 6; P<0.01 for both). Cu2+ exposure did not affect the relaxant response to NO-donors. 4 Impairment of vasorelaxation appeared 3 h after incubation with 2 muM Cu2+ and required 12 h ;to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mm tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2 +/- 6.4%, n = 10, P<0.01 VS Cu2+ alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. 5 Twenty-four hour-exposure to 2 muM Cu2+ did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8 +/- 1.1 to 18.9 +/- 2.9 ng mg(-1) wet weight, n = 8; P<0.01. 6 Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations Of Cu2+ impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions. C1 Univ Catania, Dipartimento Farmacol Sperimentale & Clin, Fac Med & Chirurg, I-95125 Catania, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Neurosci, Charlestown, MA 02129 USA. Univ Catania, Fac Med & Chirurg, Ist Igiene & Med Preventiva, I-95124 Catania, Italy. Univ Catania, Fac Med & Chirurg, Ist Anat & Istol Patol, I-95125 Catania, Italy. Univ Catholique Louvain, Pharmacol Lab, B-1200 Brussels, Belgium. RP Salomone, S (reprint author), Univ Catania, Dipartimento Farmacol Sperimentale & Clin, Fac Med & Chirurg, Viale A Doria 6, I-95125 Catania, Italy. RI Godfraind, Theophile/G-2269-2011; OI Salomone, Salvatore/0000-0001-5307-6103 NR 44 TC 9 Z9 12 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD AUG PY 2002 VL 136 IS 8 BP 1185 EP 1193 DI 10.1038/sj.bjp.0704816 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 584MZ UT WOS:000177471600016 PM 12163352 ER PT J AU Schipani, E AF Schipani, E TI Conditional gene inactivation using cre recombinase SO CALCIFIED TISSUE INTERNATIONAL LA English DT Review ID TRANSGENIC MICE; DNA RECOMBINATION; CELLS C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schipani, E (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. NR 16 TC 4 Z9 5 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD AUG PY 2002 VL 71 IS 2 BP 100 EP 102 DI 10.1007/s00223002-1004-y PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 589ZN UT WOS:000177792100002 PM 12200643 ER PT J AU Jamali, A Hilpert, A Debes, J Afshar, P Rahban, S Holmes, R AF Jamali, A Hilpert, A Debes, J Afshar, P Rahban, S Holmes, R TI Hydroxyapatite/calcium carbonate (HA/CC) vs. plaster of Paris: A histomorphometric and radiographic study in a rabbit tibial defect model SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE bone graft; calcium sulfate; hydroxy apatite; plaster of Paris; HA/CC ID POROUS HYDROXYAPATITE; BONE; IMPLANTS AB The search for an ideal bone substitute is ongoing. Multiple osteoconductive bone substitutes are available today. Plaster of Paris (POP) (calcium sulfate) has been used for more than 100 years for treatment of skeletal defects. This implant is compared to a new material, hydroxyapatite/calcium carbonate (HA/CC), in a rabbit tibia model. HA/CC is made from partial conversion of coralline calcium carbonate to hydroxyapatite and has an outer hydroxyapatite layer and an inner calcium carbonate core, a combination that leads to faster resorption than that of pure hydroxyapatite. This study compares the histomorphometric and radiographic properties of POP and HA/CC in a rabbit tibial defect. Both implants preferentially restore bone to the cortex relative to the canal. Plaster of Paris was fully resorbed by 6 weeks both radiographically and histometrically and HA/CC was substantially resorbed by 42 weeks. No significant difference was noted in volume fraction of bone between the two implants at 42 weeks postimplantation. Hydroxyapatite/calcium carbonate is a biocompatible bone graft substitute with a rate of resorption significantly slower than plaster of Paris. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ Calif San Diego, Div Plast Surg, San Diego, CA 92103 USA. Interpore Cross Int Inc, Irvine, CA USA. RP Jamali, A (reprint author), 77 Phillips St,1, Boston, MA 02114 USA. NR 19 TC 34 Z9 36 U1 0 U2 10 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD AUG PY 2002 VL 71 IS 2 BP 172 EP 178 DI 10.1007/s00223-001-1087-x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 589ZN UT WOS:000177792100012 PM 12200649 ER PT J AU Tsuang, MT Faraone, SV AF Tsuang, MT Faraone, SV TI Diagnostic concepts and the prevention of schizophrenia SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Brockton W Roxbury Vet Affairs Med Ctr, Psychiat Serv, Brockton, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [2R01-MH43518, R01-MH50647, R25-MH60485, T32-MH17119, U01-MH46318] NR 13 TC 6 Z9 6 U1 0 U2 0 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 260-441 MACLAREN ST, OTTAWA, ONTARIO K2H 2P3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD AUG PY 2002 VL 47 IS 6 BP 515 EP 517 PG 3 WC Psychiatry SC Psychiatry GA 586VX UT WOS:000177607800003 PM 12211878 ER PT J AU Tsuang, MT Stone, WS Faraone, SV AF Tsuang, MT Stone, WS Faraone, SV TI Understanding predisposition to schizophrenia: Toward intervention and prevention SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Review DE schizophrenia; schizotaxia; genetics; negative symptoms; neuropsychological deficits; schizotaxia treatment protocol ID SCHIZOTYPAL PERSONALITY-DISORDER; NONPSYCHOTIC RELATIVES; MILLENNIUM-CONSORTIUM; FAMILIAL TRANSMISSION; BIOLOGICAL RELATIVES; UNAFFECTED SIBLINGS; HIPPOCAMPAL VOLUME; SOCIAL-ADJUSTMENT; GATING DEFICITS; BRAIN STRUCTURE AB Objective: Early intervention to prevent schizophrenia is one of the most important goals of schizophrenia research. However, the field is not yet ready to initiate trials to prevent prodromal or psychotic symptoms in people who are at risk for developing the disorder. In this paper, we consider some of the major obstacles that must be studied before prevention strategies become feasible. Method and Results: One of the most important hurdles is the identification of a syndrome or set of traits that reflects a predisposition to schizophrenia and that might provide potential targets for intervention. In a recent reformulation of Paul Meehl's concept of schizotaxia, we integrate research findings obtained over the last 4 decades to propose a syndrome with meaningful clinical manifestations. We review the conceptualization of this syndrome and consider its multidimensional clinical expression. We then describe preliminary research diagnostic criteria for use in adult, nonpsychotic, first-degree relatives of patients diagnosed with schizophrenia, based on negative symptoms and neuropsychological deficits. We follow this with evidence supporting the validity of the proposed syndrome, which mainly includes social dysfunction and response to a low dosage of one of the newer antipsychotic medications. Conclusions: Continued progress toward the eventual initiation of prevention strategies for schizophrenia will include sustained efforts to validate the traits reflecting a predisposition to develop the disorder (for example, schizotaxia), follow-up studies to confirm initial findings, and the identification of potentially useful preventive interventions. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Psychiat Serv, Brockton West Roxbury VA Med Ctr, Brockton, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 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 [T32-MH17119, 2R01-MH43518, R01-MH50647, R25-MH60485, U01-MH46318] NR 78 TC 35 Z9 35 U1 0 U2 1 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 260-441 MACLAREN ST, OTTAWA, ONTARIO K2H 2P3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD AUG PY 2002 VL 47 IS 6 BP 518 EP 526 PG 9 WC Psychiatry SC Psychiatry GA 586VX UT WOS:000177607800004 PM 12211879 ER PT J AU Faraone, SV Brown, CH Glatt, SJ Tsuang, MT AF Faraone, SV Brown, CH Glatt, SJ Tsuang, MT TI Preventing schizophrenia and psychotic behaviour: Definitions and methodological issues SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Review DE schizophrenia; prevention; methodology; prodrome; premorbid; schizotaxia ID FINNISH ADOPTIVE FAMILY; FIRST-LINE TREATMENT; HIGH-RISK-PROJECT; PRENATAL EXPOSURE; PERINATAL COMPLICATIONS; OBSTETRIC COMPLICATIONS; GENETIC VULNERABILITY; SUSCEPTIBILITY LOCUS; INFLUENZA EPIDEMICS; ADULT SCHIZOPHRENIA AB Although schizophrenia onset usually occurs in late adolescence or early adulthood, much research shows that its seeds are planted early in life and that eventual onset occurs at the end of a neurodevelopmental process leading to aberrant brain functioning. This idea, along with the fact that current therapies are far from fully effective, suggests that preventive treatments may be needed to achieve an ideal outcome for schizophrenia patients and those predisposed to the disorder. In this article, we review the methodological challenges that must be overcome before effective preventive interventions can be created. Prevention studies will need to define the target population. This requires the identification of risk factors that will be useful in selecting at-risk people for preventive treatment. We review currently identified risk factors for schizophrenia: genes, psychosocial factors, pregnancy and delivery complications, and viruses. We also review 3 different types of prevention programs: universal, indicated, and selective. For schizophrenia, we distinguish prevention programs that target prodromal cases and those that target the disorder's premorbid precursors. Although those targeting prodromal cases provide a useful framework for early treatment of the disorder, studies of premorbid individuals are needed to design a truly preventive treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Univ S Florida, Biostat & Epidemiol Ctr Hlth Res, Tampa, FL USA. Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, Tampa, FL USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. W Roxbury VA Med Ctr, Psychiat Serv, Brockton, MA USA. RP Faraone, SV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. OI Brown, C Hendricks/0000-0002-0294-2419; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD040051]; NIMH NIH HHS [MH40859, R01MH43518, R01MH59624, R25MH60485] NR 128 TC 17 Z9 17 U1 6 U2 8 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 260-441 MACLAREN ST, OTTAWA, ONTARIO K2H 2P3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD AUG PY 2002 VL 47 IS 6 BP 527 EP 537 PG 11 WC Psychiatry SC Psychiatry GA 586VX UT WOS:000177607800005 PM 12211880 ER PT J AU Sorensen, G Stoddard, AM LaMontagne, AD Emmons, K Hunt, MK Youngstrom, R McLellan, D Christiani, DC AF Sorensen, G Stoddard, AM LaMontagne, AD Emmons, K Hunt, MK Youngstrom, R McLellan, D Christiani, DC TI A comprehensive worksite cancer prevention intervention: behavior change results from a randomized controlled trial (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE nutrition; occupational health; tobacco control; worksites ID HEALTH PROMOTION PROGRAMS; WHITE-COLLAR WORKERS; COLORECTAL-CANCER; INTEGRATIVE PERSPECTIVE; VEGETABLE INTAKE; RISK; WORKPLACE; WELLNESS; SMOKING; MODEL AB Objective: Workplace cancer prevention initiatives have been least successful with blue-collar workers. This study assesses whether an intervention integrating health promotion with occupational health and safety results in significant and meaningful increases in smoking cessation and consumption of fruits and vegetables, compared to a standard health promotion intervention, for workers overall and for blue-collar workers in particular. Methods: A randomized controlled design was used, with 15 manufacturing worksites assigned to a health promotion (HP) or a health promotion plus occupational health and safety intervention (HP/OHS), and compared from baseline (1997) to final (1999). The response rates to the survey were 80% at baseline (n = 9019) and 65% at final (n = 7327). Both groups targeted smoking and diet; the HP/OHS condition additionally incorporated reduction of occupational exposures. Results: Smoking quit rates among blue-collar workers in the HP/OHS condition more than doubled relative to those in the HP condition (OR = 2.13, p = 0.04), and were comparable to quit rates of white-collar workers. No statistically significant differences between groups were found for mean changes in fruits and vegetables. Conclusions: Integration of occupational health and safety and health promotion may be an essential means of enhancing the effectiveness of worksite tobacco control initiatives with blue-collar workers. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Massachusetts, Amherst, MA 01003 USA. Monash Univ Sch Med, Prahran, Vic, Australia. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5 R01 CA68087] NR 65 TC 84 Z9 84 U1 2 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2002 VL 13 IS 6 BP 493 EP 502 DI 10.1023/A:1016385001695 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 573AU UT WOS:000176807800001 PM 12195637 ER PT J AU Fairfield, KM Hunter, DJ Fuchs, CS Colditz, GA Hankinson, SE AF Fairfield, KM Hunter, DJ Fuchs, CS Colditz, GA Hankinson, SE TI Aspirin, other NSAIDs, and ovarian cancer risk (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE analgesics; anti-inflammatories; aspirin; ovarian neoplasms ID ORAL-CONTRACEPTIVE USE; WOMEN; QUESTIONNAIRE; TALC; VALIDATION; MORTALITY; DISEASE; COHORT AB Objective: We sought to evaluate the association between ovarian cancer risk and use of aspirin and nonsteroidal anti-inflammatories. Methods: We prospectively assessed use of aspirin, nonsteroidal anti-inflammatories (NSAIDs), and acetaminophen use in relation to ovarian cancer risk among 76,821 participants in the Nurses' Health Study who had no history of cancer other than non-melanoma skin cancer. Women reported known and suspected ovarian cancer risk factors in biennial mailed questionnaires from 1976 to 1996, along with new diagnoses of ovarian cancer. Aspirin use was assessed in 1980, 1982, 1984, and 1988-1994. We assessed NSAID use in 1980, and both NSAID and acetaminophen use in 1990, 1992, and 1994. During 16 years of follow-up and 1,222,412 person-years, 333 cases of invasive epithelial ovarian cancer were confirmed. We used pooled logistic regression to control for age, body mass index, oral contraceptive use, smoking history, parity, postmenopausal hormone use, tubal ligation, and other potential ovarian cancer risk factors. Results: Aspirin use was not associated with ovarian cancer risk overall (RR for users compared with nonusers, 1.00, 95% confidence interval (CI 0.80-1.25). We found no association between aspirin dose (in number of weekly tablets) and ovarian cancer risk (RR for those taking 15 or more tablets weekly compared with nonusers, 0.98, 95% CI 0.63-1.52). Similarly, duration of aspirin use was not associated with risk (RR for aspirin use of 20 or more years, 0.99, 95% CI 0.69-1.43). In separate models assessing the relation between NSAID use and ovarian cancer risk we found a 40% reduction in risk among NSAID users versus nonusers (RR 0.60, 95% CI 0.38-0.95). However, when we examined this relationship in terms of days of NSAID use per month, we did not observe a dose-response with increasing NSAID use. Conclusions: We observed no association between aspirin use, dose, or duration and epithelial ovarian cancer risk. Although we found a modest reduction in risk associated with NSAID use, there was no dose-effect. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Fairfield, KM (reprint author), Channing Labs, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA87969] NR 30 TC 44 Z9 46 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2002 VL 13 IS 6 BP 535 EP 542 DI 10.1023/A:1016380917625 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 573AU UT WOS:000176807800007 PM 12195643 ER PT J AU O'Hagan, RC Chang, S Maser, RS Mohan, R Artandi, SE Chin, L DePinho, RA AF O'Hagan, RC Chang, S Maser, RS Mohan, R Artandi, SE Chin, L DePinho, RA TI Telomere dysfunction provokes regional amplification and deletion in cancer genomes SO CANCER CELL LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; HUMAN COLORECTAL-CANCER; BREAST-CANCER; CHROMOSOME BREAKAGE; GENE AMPLIFICATION; OVARIAN-CARCINOMA; CELL-CYCLE; TUMORS; DNA; MICE AB Telomere dysfunction and associated fusion-breakage in the mouse encourages epithelial carcinogenesis and a more humanized genomic profile that includes nonreciprocal translocations (NRTs). Here, array comparative genomic hybridization was used to determine the pathogenic significance of NRTs and to determine whether telomere dysfunction also drives amplifications and deletions of cancer-relevant loci. Compared to tumors arising in mice with intact telomeres, tumors with telomere dysfunction possessed higher levels of genomic instability and showed numerous amplifications and deletions in regions syntenic to human cancer hotspots. These observations suggest that telomere-based crisis provides a mechanism of chromosomal instability, including regional amplifications and deletions, that drives carcinogenesis. This model provides a platform for discovery of genes responsible for the major cancers affecting aged humans. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Maser, Richard/B-2970-2012 FU NIA NIH HHS [K08 AG001019, 1KO8AG01019-01] NR 53 TC 165 Z9 173 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 AUG PY 2002 VL 2 IS 2 BP 149 EP 155 DI 10.1016/S1535-6108(02)00094-6 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599UB UT WOS:000178352600010 PM 12204535 ER PT J AU Dolmans, DEJGJ Kadambi, A Hill, JS Flores, KR Gerber, JN Walker, JP Rinkes, IHMB Jain, RK Fukumura, D AF Dolmans, DEJGJ Kadambi, A Hill, JS Flores, KR Gerber, JN Walker, JP Rinkes, IHMB Jain, RK Fukumura, D TI Targeting tumor vasculature and cancer cells in orthotopic breast tumor by fractionated photosensitizer dosing photodynamic therapy SO CANCER RESEARCH LA English DT Article ID IN-VIVO; MICROCIRCULATION; PERMEABILITY; ANGIOGENESIS; CARCINOMA; PORPHYRIN; GROWTH; MODEL AB Photodynamic therapy (PDT) is a locally administered therapy currently being investigated in various clinical and preclinical settings. Tumor-host interaction is an important determinant of tumor biology and response to treatments. Here we report for the first time the effects of PDT on an orthotopic, murine mammary tumor model. PDT utilizes two individually nontoxic components: (a) the localization in the target site of a photosensitizing drug; and (b) the activation of the photosensitizer by light of an appropriate wavelength and energy. PDT after a single dose of the photosensitizer MV6401 induced drug dose-dependent, long-term blood flow shut down and tumor growth delay in the MCaIV tumor, grown in the mammary fat pad. The plasma half-life of MV6401 was similar to20 min, and the drug was confined to the vascular compartment shortly after administration. However, it accumulated in the interstitial compartment at 2-6 h after the administration. Two equal MV6401 doses injected 4 h and 15 min before the light administration allowed the photosensitizer to localize in both vascular and tumor cell compartments. The fractionated drug dose PDT more effectively induced tumor growth delay than the same total dose given as a single dose either at 4 h or at 15 min before light administration. The long-term effect of the fractionated drug PDT on blood flow was also more extensive than single-dose PDT. Fractionated photosensitizer dosing PDT offers a new strategy to optimize PDT therapy. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med,Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. Mirvant Med Technol, Santa Barbara, CA 93117 USA. Univ Utrecht, Ctr Med, Dept Surg, Utrecht, Netherlands. RP Fukumura, D (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med,Edwin L Steele Lab Tumor Biol, 100 Blossom St,Cox 734, Boston, MA 02114 USA. FU NCI NIH HHS [P01-CA80124] NR 28 TC 65 Z9 77 U1 1 U2 15 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 AUG 1 PY 2002 VL 62 IS 15 BP 4289 EP 4294 PG 6 WC Oncology SC Oncology GA 578EZ UT WOS:000177105600020 PM 12154031 ER PT J AU Chakravarti, A Chakladar, A Delaney, MA Latham, DE Loeffler, JS AF Chakravarti, A Chakladar, A Delaney, MA Latham, DE Loeffler, JS TI The epidermal growth factor receptor pathway mediates resistance to sequential administration of radiation and chemotherapy in primary human glioblastoma cells in a RAS-dependent manner SO CANCER RESEARCH LA English DT Article ID FARNESYL TRANSFERASE INHIBITORS; MONOCLONAL-ANTIBODY C225; HUMAN CANCER-CELLS; SIGNAL-TRANSDUCTION; PHASE-I; PHOSPHATIDYLINOSITOL 3-KINASE; INDEPENDENT SURVIVAL; IONIZING-RADIATION; ANTITUMOR-ACTIVITY; HUMAN ASTROCYTOMAS AB Resistance to conventional adjuvant therapies (i.e., chemotherapy and radiation) has been well documented in malignant gliomas. Unlike many other tumor types, combined modality therapy involving radiation and chemotherapy has failed to appreciably enhance outcome for glioblastoma patients compared with radiation alone. In vitro, we have observed an actual antagonistic effect between sequential administration of radiation and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) chemotherapy in three primary human glioblastoma cell lines (referred as the GBME3-5 cell lines), which also happen to demonstrate strong expression of the epidermal growth factor receptor (EGFR). Upon inhibition of EGFR with the EGFR tyrosine kinase inhibitor, AG1478, it was found that this cross-resistance between sequential administration of radiation and BCNU was abrogated. To dissect which of these pathways may be responsible for the observed antagonism, known EGFR-regulated downstream signaling pathways including RAS, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase (p44/p42), and protein kinase C were inactivated with both pharmacological inhibitors and transient transfection experiments with dominant-negative and constitutively active constructs in the presence of exogenous EGF stimulation. It was found that BCNU inhibited radiation-induced apoptosis through EGFR-mediated activation of PI3-K/AKT via RAS. On the other hand, radiation was found to inhibit BCNU-induced apoptosis through EGFR-mediated activation of both PI3-K and mitogen-activated protein kinase (p44/p42) pathways, also via RAS. Inhibition of either EGFR or RAS activity appears to not only abrogate the observed antagonism between sequentially administered radiation and chemotherapy but actually results in a greater enhancement of apoptosis in the setting of combined modality therapy than when administered with either radiation or chemotherapy as single agents. Therefore, these findings suggest that strategies to inactivate EGFR or RAS signaling may be critical to improving not only the efficacy of single-agent therapy but also of combined modality therapy in gliomas. C1 Harvard Univ, Oncol Mol Lab, Massachusetts Gen Hosp, Sch Med,Dept Radiat Oncol, Charlestown, MA 02129 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. RP Chakravarti, A (reprint author), Harvard Univ, Oncol Mol Lab, Massachusetts Gen Hosp, Sch Med,Dept Radiat Oncol, 13th St,Bldg 149,Room 7330, Charlestown, MA 02129 USA. FU NCI NIH HHS [KO8CA82163] NR 64 TC 137 Z9 146 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2002 VL 62 IS 15 BP 4307 EP 4315 PG 9 WC Oncology SC Oncology GA 578EZ UT WOS:000177105600023 PM 12154034 ER PT J AU Liu, XM Chapman, GB Peyton, KJ Schafer, AI Durante, W AF Liu, XM Chapman, GB Peyton, KJ Schafer, AI Durante, W TI Carbon monoxide inhibits apoptosis in vascular smooth muscle cells SO CARDIOVASCULAR RESEARCH LA English DT Article DE apoptosis; arteries; cell culture/isolation; cytokines; smooth muscle ID SPONTANEOUSLY HYPERTENSIVE RATS; NECROSIS-FACTOR-ALPHA; HEME OXYGENASE; EXPRESSION; PROTEIN; MECHANISMS; INTERLEUKIN-1-BETA; ATHEROSCLEROSIS; INDUCTION; ENZYME AB Objective: Carbon monoxide (CO) is generated from vascular smooth muscle cells via the degradation of heme by the enzyme heme oxygenase-1. Since smooth muscle cell apoptosis is associated with numerous vascular disorders, we investigated whether CO regulates apoptosis in vascular smooth muscle. Methods and Results: Treatment of cultured rat aortic smooth muscle cells with a combination of cytokines (interleukin-1beta, 5 ng/ml; tumor necrosis factor-alpha, 20 ng/ml; interferon-gamma, 200 U/ml) for 48 h stimulated apoptosis, as demonstrated by DNA laddering, annexin V binding, and caspase-3 activation. However, the exogenous administration of CO inhibited cytokine-mediated apoptosis. The antiapoptotic action of CO was partially dependent on the activation of soluble guanylate cyclase and was associated with the inhibition of mitochondrial cytochrome c release and with the suppression of p53 expression. Incubation of smooth muscle cells with the cytokines also resulted in a pronounced increase in heme oxygenase-1 protein after 24 h of stimulation. The addition of the heme oxygenase inhibitor, zinc protoporphyrin-IX, or the CO scavenger, hemoglobin, stimulated apoptosis following 24 h of cytokine exposure. Conclusions: These results demonstrate that CO, either administered exogenously or endogenously derived from heme oxygenase-1 activity, inhibits vascular smooth muscle cell apoptosis. The ability of CO to block smooth muscle cell apoptosis may play an important role in blocking lesion formation at sites of vascular injury. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. RP Durante, W (reprint author), Houston VA Med Ctr, Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL36045, HL59976, HL62467] NR 42 TC 121 Z9 127 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD AUG 1 PY 2002 VL 55 IS 2 BP 396 EP 405 AR PII S0008-6363(02)00410-8 DI 10.1016/S0008-6363(02)00410-8 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 582MQ UT WOS:000177355500024 PM 12123779 ER PT J AU Fan, VS Curtis, JR Tu, SP McDonell, MB Fihn, SD AF Fan, VS Curtis, JR Tu, SP McDonell, MB Fihn, SD CA Ambulatory Care Qual Improvement TI Using quality of life to predict hospitalization and mortality in patients with obstructive lung diseases SO CHEST LA English DT Article DE hospitalization; mortality; obstructive lung diseases; quality of life ID PULMONARY-DISEASE; OF-LIFE; CO-MORBIDITY; PROGNOSIS; OUTCOMES; EXACERBATION; ASTHMA; CARE AB Study objectives: Condition-specific nreasures of quality of life (QOL) for patients with COPD have been demonstrated to be highly reliable and valid, but they have not conclusively been shown to predict hospitalization or death. Objective: We sought to determine whether a brief, self-administered, COPD-specific QOL measure, the Seattle Obstructive Lung Disease Questionnaire (SOLDQ), could accurately predict hospitalizations and death. Design: Prospective cohort study. Setting. Patients enrolled in the primary care clinics at seven Department of Veterans Affairs (VA) medical centers participating in the Ambulatory Care Quality Improvement Project. Patients: Of 24,458 patients who completed a health inventory, 5,503 reported having chronic lung disease. The 3,282 patients who completed the baseline SOLDQ were followed for 12 months. Measurements: Hospitalization and all-cause mortality during the 1-year follow-up period. Results: During the follow-up period, 601 patients (18.3%) were hospitalized, 141 (4.3%) for COPD exacerbations, and 167 patients (5.1%) died. After adjusting for age, VA. hospital site, distance to die VA hospital, employment status, and smoking status, die relative risk of any hospitalization among patients with scores on the emotional, physical, and coping skills scales of the SOLDQ that were in the lowest quartile, when compared to the highest quartile, were 2.0 (95% confidence interval [CI], 1.5 to 2.6), 2.5 (95% CI, 1.9 to 3.4), and 1.9 (95% CI, 1.5 to 2.5), respectively. When hospitalizations were restricted to those specifically for COPD, the odds ratio (OR) for the lowest quartile of physical function was 6.0 (95% CI, 3.1 to 11.5). Similarly, patients in the lowest quartile of physical function also had an increased risk of death (OR, 6.8; 95% CI, 3.3 to 13.8). When adjusted for comorbidity (OR, 0.8; 95% CI, 0.5 to 1.2), long-term steroid use (OR, 2.8; 95% CI, 1.6 to 4.9), and prior hospitalization for COPD (OR, 4.5; 95% CI, 2.2 to 9.2), patients having baseline SOLDQ physical function scores in the lowest quartile had an odds of hospitalization for COPD that was fivefold higher than patients with scores in the highest quartile (OR, 5.0; 95% CI, 2.6 to 9.7). Conclusions: Lower QOL is a powerful predictor of hospitalization and an-cause mortality. Brief, self-administered instruments such as the SOLDQ may provide an opportunity to identify patients who could benefit from preventive interventions. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Fan, VS (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 25 TC 123 Z9 126 U1 1 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2002 VL 122 IS 2 BP 429 EP 436 DI 10.1378/chest.122.2.429 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 584CJ UT WOS:000177449400012 PM 12171813 ER PT J AU Kayani, S Shannon, DC AF Kayani, S Shannon, DC TI Adverse Behavioral effects of treatment for acute exacerbation of asthma in children - A comparison of two doses of oral steroids SO CHEST LA English DT Article DE adverse effects; asthma; benefit; prednisolone; prednisome; side effects; therapeutic use ID PREDNISONE AB Objective: To determine the relative adverse symptomatic effects and benefits of therapy with oral corticosteroids at doses of 2 mg/kg vs 1 mg/kg daily in children with acute exacerbations of asthma. Methods: Using a questionnaire that addressed symptoms, we conducted a prospective study of the adverse effects and benefits of therapy with prednisone or prednisolone at two dose levels in 86 children who were 2 to 16 years of age with mild persistent asthma during an acute exacerbation and were unresponsive to therapy with inhaled steroids and beta-adrenergic agents. Parents and physicians were blinded to the dose level. Children were assigned to either of the two doses by random allocation. Behavioral side effects were assessed via a questionnaire administered by a physician. Benefits were measured by the resolution of asthma symptoms (cough, shortness of breath, and wheeze) at the completion of the treatment with oral steroids. Results: Behavioral side effects, particularly anxiety (p < 0.02) and aggressive behavior (p < 0.002), were twice as common in patients receiving a dose of 2 mg/kg/d. Benefits were comparable in the two groups. The number needed to harm (ie, the number of patients receiving experimental treatment that would lead to one additional person being harmed vs patients receiving standard treatment) was 6.1 for anxiety, 8.6 for hyperactivity, and 4.8 for aggressive behavior. Conclusions: Because the adverse side effects were greater at the higher dose but the benefits were comparable, recommend using an oral corticosteroid dose of 1 mg/kg daily for children with mild persistent asthma who present with an acute exacerbation of asthma. C1 Massachusetts Gen Hosp, Pediat Pulm Unit, Boston, MA 02114 USA. Bridgeport Hosp, Dept Pediat, Bridgeport, CT USA. RP Shannon, DC (reprint author), Massachusetts Gen Hosp, Pediat Pulm Unit, VBK BA015,Fruit St, Boston, MA 02114 USA. NR 14 TC 65 Z9 68 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2002 VL 122 IS 2 BP 624 EP 628 DI 10.1378/chest.122.2.624 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 584CJ UT WOS:000177449400041 PM 12171842 ER PT J AU Kleerup, EC Koyal, SN Marques-Magallanes, JA Goldman, MD Tashkin, DP AF Kleerup, EC Koyal, SN Marques-Magallanes, JA Goldman, MD Tashkin, DP TI Chronic and acute effects of "crack" cocaine on diffusing capacity, membrane diffusion, and pulmonary capillary blood volume in the lung SO CHEST LA English DT Article DE capillary blood volume; cocaine base; cocaine hydrochloride; diffusing capacity; membrane diffusion; tobacco; transfer factor ID CARBON-MONOXIDE; NORMAL VALUES; SMOKERS; USERS; PERMEABILITY; DYSFUNCTION; MARIJUANA; ABUSERS; SMOKING; TOBACCO AB Study objectives: To evaluate possible alterations in the diffusing capacity of the lung for carbon monoxide (DLCO) or its components, membrane diffusing capacity of the lung for carbon monoxide (DMCO) and pulmonary capillary blood volume (Vc), in habitual smokers of "crack" cocaine (with or without tobacco) and following the short-term administration of inhaled cocaine base or IV cocaine HCl. Design: Cross-sectional and longitudinal evaluation of DLCO and its components in smokers of cocaine alone, tobacco alone, and cocaine plus tobacco, and in nonsmokers and ex-smokers. Measurement of possible acute effects on DLCO and its components after experimental short-term administration of IV and smoked cocaine. Setting: University and Veterans Affairs hospital research laboratories. Participants: Convenience sample of habitual smokers of crack cocaine with or without tobacco and matched control nonsmokers and ex-smokers, and smokers of tobacco only. Measurements: DLCO, DMCO, and Vc. Conclusions: Neither habitual cocaine smoking in cross-sectional or longitudinal analysis nor the short-term administration of inhaled alkaloidal cocaine significantly affected DLCO or its component parts. In contrast, a clear cross-sectional effect of regular tobacco smoking was demonstrated. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Kleerup, EC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care, CHS 37-131,Box 951690, Los Angeles, CA 90095 USA. FU NIDA NIH HHS [R01 DA08254, R01 DA008254] NR 41 TC 7 Z9 8 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2002 VL 122 IS 2 BP 629 EP 638 DI 10.1378/chest.122.2.629 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 584CJ UT WOS:000177449400042 PM 12171843 ER PT J AU Stephen, AE Pearsall, LA Christian, BP Donahoe, PK Vacanti, JP MacLaughlin, DT AF Stephen, AE Pearsall, LA Christian, BP Donahoe, PK Vacanti, JP MacLaughlin, DT TI Highly purified Mullerian inhibiting substance inhibits human ovarian cancer in vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN-TUMOR XENOGRAFTS; NUDE-MICE; CELL-GROWTH; IN-VIVO; EXPRESSION; HORMONE; INVITRO; PURIFICATION; CULTURE; CAPSULE AB Purpose: Mullerian inhibiting substance (MIS) causes Mullerian duct regression in mammalian, avian, and reptilian embryos; MIS also inhibits growth in vitro of Mullerian-derived cell lines and primary cells from human ovarian carcinomas. We hypothesize that highly purified MIS delivered parenterally inhibits ovarian cancer in vivo. Experimental Design: To test the efficacy of highly purified MIS against ovarian cancer cell lines in vivo, we treated immunosuppressed mice with MIS after implanting OVCAR 8 or IGROV 1 human ovarian cancer cells beneath the renal capsules and measured tumor volume over time. Animals were treated with daily injections of 10 mug of purified exogenous recombinant human MIS or by endogenous MIS secreted from cells growing on biodegradable mesh. Results: The average graft size ratio (change in size compared with starting size) of the OVCAR 8 tumor implants was larger in the control animals than in animals treated for 2 weeks (P < 0.019) or 3 weeks (P < 0.001) with parenteral MIS, or after treating with MIS produced from transfected cells, which impregnated the biodegradable mesh (P = 0.02). The average graft size ratio of the IGROV I tumors was also larger in the control animals than in those treated with injected MIS (P = 0.0174). Conclusions: Highly purified recombinant human MIS, delivered parenterally, or MIS produced endogenously causes inhibition of human ovarian cancer cell lines in vivo, providing convincing preclinical evidence to support the use of MIS as a parenteral agent for the treatment of ovarian cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Tissue Engn & Organ Fabricat,Dept Surg, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, 55 Fruit St,Warren 10, Boston, MA 02114 USA. EM maclaugh@helix.mgh.harvard.edu FU NCI NIH HHS [T 32CA71345-06, CA71345-04, R01CA17393]; NICHD NIH HHS [5R01HD-32112-08] NR 36 TC 41 Z9 44 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 2002 VL 8 IS 8 BP 2640 EP 2646 PG 7 WC Oncology SC Oncology GA 585JB UT WOS:000177520700026 PM 12171896 ER PT J AU Dore, MP Malaty, HM Graham, DY Fanciulli, G Delitala, G Realdi, G AF Dore, MP Malaty, HM Graham, DY Fanciulli, G Delitala, G Realdi, G TI Risk factors associated with Helicobacter pylori infection among children in a defined geographic area SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SOCIOECONOMIC-STATUS; DIAGNOSTIC-TESTS; CHILDHOOD; AGE; EPIDEMIOLOGY; COMMUNITY; COHORT; SEROEPIDEMIOLOGY; TRANSMISSION; PREVALENCE AB Factors influencing the pattern of Helicobacter pylori infection among children living in adjacent urban and rural areas of northern Sardinia, Italy, were compared. The seroprevalence of H. pylori infection was 22% (625 of 2810 children) in the study population and was significantly higher among children in rural areas (37%) than in urban areas (13%) (odds ratio [OR], 3. 8; 95% confidence interval [CI], 3.2- 4.7; P < .005). This difference was consistent within each age group. In rural areas, children who had dogs were at greatest risk for H. pylori infection (OR, 1.8; 95% CI, 1.3-2.6; P < .05). No association was seen between H. pylori seropositivity and a history of breast-feeding. Urban children attending day care centers had a higher prevalence of infection (17%) than did those who never attended (12%) (OR, 1.5; 95% CI, 1.1-2.0; P < .05). The epidemiology of H. pylori infection is complex; even within the same geographic area, different factors influence acquisition of H. pylori infection. C1 Univ Sassari, Ist Clin Med, I-07100 Sassari, Italy. Univ Sassari, Inst Patol Med, I-07100 Sassari, Italy. VA Med Ctr, Gastrointestinal Sect, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Dore, MP (reprint author), Univ Sassari, Ist Clin Med, Viale San Pietro 8, I-07100 Sassari, Italy. NR 34 TC 45 Z9 46 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2002 VL 35 IS 3 BP 240 EP 245 DI 10.1086/341415 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 573QA UT WOS:000176841300004 PM 12115088 ER PT J AU Barouch, DH Faquin, WC Chen, YP Koralnik, IJ Robbins, GK Davis, BT AF Barouch, DH Faquin, WC Chen, YP Koralnik, IJ Robbins, GK Davis, BT TI BK virus-associated hemorrhagic cystitis in a human immunodeficiency virus-infected patient SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; JC-VIRUS; ANTIRETROVIRAL THERAPY; POLYOMAVIRUS INFECTION; AIDS; CIDOFOVIR; NEPHRITIS; RECIPIENTS; IMPROVES; REGIONS AB BK virus-associated hemorrhagic cystitis is a common clinical problem in bone marrow transplant recipients but is considered rare in other immunosuppressed patient populations. We describe a human immunodeficiency virus-infected patient with non-Hodgkin's lymphoma in whom BK virus-associated hemorrhagic cystitis developed; viruria was quantitated in urine by immunocytochemistry, and the patient showed no response to cidofovir. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Barouch, DH (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 5,55 Fruit St, Boston, MA 02114 USA. NR 23 TC 28 Z9 29 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 AUG 1 PY 2002 VL 35 IS 3 BP 326 EP 329 DI 10.1086/341491 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 573QA UT WOS:000176841300017 PM 12115100 ER PT J AU Lucey, BC Maher, MM Gervais, DA Mueller, PR AF Lucey, BC Maher, MM Gervais, DA Mueller, PR TI Bacterial peritonitis: A postulated cause of death associated with hepatic radiofrequency ablation SO CLINICAL RADIOLOGY LA English DT Editorial Material ID PERCUTANEOUS ETHANOL INJECTION; SMALL HEPATOCELLULAR-CARCINOMA; RESECTION; CIRRHOSIS; CANCER C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Lucey, BC (reprint author), Ayazma Mah Velioglu Sok No 9-7,Husnufirat Apt, TR-81160 Istanbul, Turkey. NR 11 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD AUG PY 2002 VL 57 IS 8 BP 765 EP 767 DI 10.1053/crad.2002.0975 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586NY UT WOS:000177591100015 PM 12169291 ER PT J AU Sever, S AF Sever, S TI Dynamin and endocytosis SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID CLATHRIN-MEDIATED ENDOCYTOSIS; RATE-LIMITING STEP; VESICLE FORMATION; GTPASE; DOMAIN; CONFORMATION; GENERATION; MEMBRANES; ASSEMBLES; MECHANISM AB The GTPase dynamin is essential for endocytosis, but its mechanism of action remains uncertain. Structures of its GTPase domain, as well as that of assembled dynamin, have led to major advances in understanding the structural basis of its mode of action. Novel data point more clearly than ever towards a role for this protein in the actin cytoskeleton, mitogen-activated protein kinase signaling and apoptosis, suggesting that dynamin might be a signaling GTPase. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sever, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 1 Jimmy Fund Way, Boston, MA 02115 USA. NR 44 TC 92 Z9 95 U1 0 U2 7 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 AUG PY 2002 VL 14 IS 4 BP 463 EP 467 DI 10.1016/S0955-0674(02)00347-2 PG 5 WC Cell Biology SC Cell Biology GA 570XN UT WOS:000176685900010 PM 12383797 ER PT J AU Lieberman, J Manjunath, N Shankar, P AF Lieberman, J Manjunath, N Shankar, P TI Avoiding the kiss of death: how HIV and other chronic viruses survive SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; RECEPTOR ZETA-CHAIN; EPSTEIN-BARR-VIRUS; IN-VIVO; EFFECTOR FUNCTION; PERFORIN GENE; VIRAL-INFECTION; LYMPHOCYTE RESPONSES; SIGNALING MOLECULES AB Virus-specific CD8 T cells during chronic infection often exceed in numbers virus-replicating infected cells. Why then do antiviral CD8 T cells not do a better job of controlling infection? Although viral strategies for immune evasion are well known, this review will focus on changes in the CD8 T cell that interfere with cytolytic function. Most antiviral CD8 T cells in chronic infection do not express perforin, a molecule that is required for cytolysis. IL-2 and other costimulatory signals can restore cytotoxicity that has been impaired, suggesting a role for CD4 T cell anergy. The chance to eradicate an infection by T cell mediated lysis is undermined after an infection becomes established, in part because the effector immune response is impaired in the setting of chronic antigen. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI42519, AI45406] NR 80 TC 31 Z9 31 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 AUG PY 2002 VL 14 IS 4 BP 478 EP 486 DI 10.1016/S0952-7915(02)00366-7 PG 9 WC Immunology SC Immunology GA 567MG UT WOS:000176488100011 PM 12088683 ER PT J AU Gandhi, RT Walker, BD AF Gandhi, RT Walker, BD TI Promises and pitfalls in the reconstitution of immunity in patients who have HIV-1 infection SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CYTOTOXIC T-LYMPHOCYTE; SUSTAINED VIRAL SUPPRESSION; FAS LIGAND EXPRESSION; CELL RESPONSES; EFFECTOR FUNCTION; CONTROLLED TRIAL; CD4(+); AIDS AB Recent studies suggest that immunologic containment of HIV-1 is possible and the immune correlates of this control are being defined. There have been significant advances in our ability to elicit virus-specific immune responses, which have led to viral control in animal models. Although viral escape from the immune system is an important challenge, new strategies for therapeutic and preventative HIV-1 vaccination are being vigorously pursued in human trials. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02114 USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 69 TC 12 Z9 13 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 AUG PY 2002 VL 14 IS 4 BP 487 EP 494 DI 10.1016/S0952-7915(02)00359-X PG 8 WC Immunology SC Immunology GA 567MG UT WOS:000176488100012 PM 12088684 ER PT J AU Ferrantelli, F Ruprecht, RM AF Ferrantelli, F Ruprecht, RM TI Neutralizing antibodies against HIV - back in the major leagues? SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; DEPENDENT CELLULAR CYTOTOXICITY; HIV-1/SIV CHIMERIC VIRUS; CD4 BINDING-SITE; PASSIVE-IMMUNIZATION; RHESUS MACAQUES; SYNERGISTIC NEUTRALIZATION; IMMUNE-RESPONSES; CD4-BINDING SITE AB The past few months have seen encouraging successes for neutralizing antibodies against HIV; human monoclonal antibodies targeting conserved HIV envelope epitopes potently neutralized primary virus isolates, including strains of different clades. In primates, passive immunization with combinations containing human monoclonal antibodies completely prevented infection, even after mucosal virus challenges. Epitopes recognized by the protective monoclonal antibodies are important determinants for protection and provide a rational basis for AIDS vaccine development. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ferrantelli, F (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RI Ferrantelli, Flavia/J-7794-2016 OI Ferrantelli, Flavia/0000-0002-0768-1078 FU NIAID NIH HHS [P01 AI48240, R01 AI34266] NR 67 TC 82 Z9 84 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2002 VL 14 IS 4 BP 495 EP 502 DI 10.1016/S0952-7915(02)00362-X PG 8 WC Immunology SC Immunology GA 567MG UT WOS:000176488100013 PM 12088685 ER PT J AU Reddy, A Kaelin, WG AF Reddy, A Kaelin, WG TI Using cancer genetics to guide the selection of anticancer drug targets SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID GASTROINTESTINAL STROMAL TUMORS; ABL TYROSINE KINASE; SYNTHETIC LETHALITY SCREEN; CHRONIC MYELOID-LEUKEMIA; CULTURED HUMAN-CELLS; C-KIT; MOLECULAR CLASSIFICATION; CLINICAL IMPLICATIONS; EXPRESSION PATTERNS; DROSOPHILA P53 AB The genetic alterations that cause cancer are coming into view. Genes that are recurrently mutated in a particular form of human cancer flag the proteins (or molecular pathways) that are critical for the evolution of that malignancy. The first generation of anticancer agents prospectively guided by these principles, for which imatinib mesylate is a prototype, inhibit the biochemical activities that result from gain-of-function oncogenic mutations. Advances in somatic cell genetics and chemical biology should facilitate the development of a second generation of agents that will inhibit proteins that are selectively required for survival in the context of specific cancer-causing mutations, whether loss-of-function or gain-of-function. C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Reddy, A (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. NR 56 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD AUG PY 2002 VL 2 IS 4 BP 366 EP 373 DI 10.1016/S1471-4892(02)00178-9 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 573PJ UT WOS:000176839800003 PM 12127868 ER PT J AU Sze, JY Zhang, SY Li, J Ruvkun, G AF Sze, JY Zhang, SY Li, J Ruvkun, G TI The C-elegans POU-domain transcription factor UNC-86 regulates the tph-1 tryptophan hydroxylase gene and neurite outgrowth in specific serotonergic neurons SO DEVELOPMENT LA English DT Article DE C. elegans; POU domain; transcription; neuron identity; neurotransmitter; serotonin; serotonin reuptake inhibitors; axon guidance ID NEMATODE CAENORHABDITIS-ELEGANS; NERVOUS-SYSTEM; CELL LINEAGE; DOPAMINERGIC-NEURONS; HOMEODOMAIN PROTEIN; DIFFERENTIATION; MEC-3; NEUROTRANSMITTER; EXPRESSION; MUTATIONS AB A fundamental question in developmental neurobiology is how a common neurotransmitter is specified in different neuronal types?. We describe cell-specific regulation of the serotonergic phenotype by the C. elegans POU-transcription factor UNC-86. We show that unc-86 regulates particular aspects of the terminal neuronal identity in four classes of serotonergic neurons, but that the development of the ADF serotonergic neurons is regulated by an UNC-86-independent program. In the NSM neurons, the role of unc-86 is confined in late differentiation; the neurons are generated but do not express genes necessary for serotonergic neurotransmission. unc-86-null mutations affect the expression in NSM of tph-1, which encodes the serotonin synthetic enzyme tryptophan hydroxylase, and cat-1, which encodes a vesicular transporter that loads serotonin into synaptic vesicles, suggesting that unc-86 coordinately regulates serotonin synthesis and packaging. However, unc-86-null mutations do not impair the ability of NSM to reuptake serotonin released from the ADF serotonergic chemosensory neurons and this serotonin reuptake is sensitive to the serotonin reuptake block drugs imipramine and fluoxetine, demonstrating that serotonin synthesis and reuptake is regulated by distinct factors. The NSM neurons in unc-86-null mutants also display abnormal neurite outgrowth, suggesting a role of unc-86 in regulating this process as well. C1 Univ Calif Irvine, Coll Med, Dept Anat & Neurobiol, Irvine, CA 92697 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Univ Calif Irvine, Coll Med, Dept Anat & Neurobiol, Irvine, CA 92697 USA. EM jsze@uci.edu NR 58 TC 49 Z9 54 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD AUG PY 2002 VL 129 IS 16 BP 3901 EP 3911 AR UNSP DEV8904 PG 11 WC Developmental Biology SC Developmental Biology GA 591EV UT WOS:000177867500013 PM 12135927 ER PT J AU Guo, J Chung, U Kondo, H Bringhurst, FR Kronenberg, HM AF Guo, J Chung, U Kondo, H Bringhurst, FR Kronenberg, HM TI The PTH/PTHrP receptor can delay chondrocyte hypertrophy in vivo without activating phospholipase C SO DEVELOPMENTAL CELL LA English DT Article ID HORMONE-RELATED PEPTIDE; PROTEIN-KINASE-C; ENDOCHONDRAL BONE-DEVELOPMENT; GROWTH-PLATE CHONDROCYTES; PARATHYROID-HORMONE; (PTH)/PTH-RELATED PEPTIDE; INDIAN HEDGEHOG; OSTEOBLASTIC CELLS; SIGNAL-TRANSDUCTION; TARGETED DISRUPTION AB One G protein-coupled receptor (GPCR) can activate more than one G protein, but the physiologic importance of such activation has not been demonstrated in vivo. We have generated mice expressing exclusively a mutant form of the PTH/PTHrP receptor (DSEL) that activates adenylyl cyclase normally but not phospholipase C (PLC). DSEL mutant mice exhibit abnormalities in embryonic endochondral bone development, including delayed ossification and increased chondrocyte proliferation. Analysis of the differentiation of embryonic metatarsals in vitro shows that PTH(1-34) and forskolin inhibit, whereas active phorbol ester stimulates, hypertrophic differentiation. Thus, PLC signaling via the PTH/PTHrP receptor normally slows the proliferation and hastens the differentiation of chondrocytes, actions that oppose the dominant effects of PTH/PTHrP receptors and that involve cAMP-dependent signaling pathways. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK11794] NR 60 TC 74 Z9 75 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD AUG PY 2002 VL 3 IS 2 BP 183 EP 194 DI 10.1016/S1534-5807(02)00218-6 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 581ZR UT WOS:000177325700009 PM 12194850 ER PT J AU Kennedy, DN Makris, N Herbert, MR Takahashi, T Caviness, VS AF Kennedy, DN Makris, N Herbert, MR Takahashi, T Caviness, VS TI Basic principles of MRI and morphometry studies of human brain development SO DEVELOPMENTAL SCIENCE LA English DT Article ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; CLINICAL-APPLICATIONS; DIFFUSION ANISOTROPY; SENSORY STIMULATION; COORDINATE SYSTEM; IN-VIVO; SEGMENTATION; TENSOR; CORTEX AB Magnetic resonance imaging has undergone dramatic development in the past years. This has been paralleled by developments in the tools for extracting quantitative information from these images in support of capturing the anatomic features of brain development in living humans. This has revolutionized our expectations for current and future diagnostic and investigative work with the developing brain. This paper will cover the classes of information that are readily available in the MR image, the mechanisms for extracting quantitative results, and a sample of the application of these types of methods to developmental issues. These applications highlight tissue- and anatomic-based contrasts in the nature and rate of developmental maturation within the brain. This will be followed by a discussion of the emergent themes of developmental science as elucidated by these classes of observation. C1 Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. MGH, MIT, HMS, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. RP Kennedy, DN (reprint author), MGH, CMA, 149 13th St, Charlestown, MA 02129 USA. NR 61 TC 13 Z9 13 U1 3 U2 5 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1363-755X J9 DEVELOPMENTAL SCI JI Dev. Sci. PD AUG PY 2002 VL 5 IS 3 BP 268 EP 278 DI 10.1111/1467-7687.00366 PG 11 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 580DV UT WOS:000177220500003 ER PT J AU Abdi, R Smith, RN Makhlouf, L Najafian, N Luster, AD Auchincloss, H Sayegh, MH AF Abdi, R Smith, RN Makhlouf, L Najafian, N Luster, AD Auchincloss, H Sayegh, MH TI The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection SO DIABETES LA English DT Article ID RENAL-TRANSPLANT REJECTION; T-CELLS; IN-VIVO; IMMUNE-RESPONSE; IFN-GAMMA; EXPRESSION; TH1; COSTIMULATION; LYMPHOCYTES; CYTOKINES AB Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4(+) T helper 1 (Th1) cells. We sought to determine the role of CCR5 in islet allograft rejection in a streptozotmin-induced diabetic mouse model. BALB/c islet allografts transplanted. into CCR5(-/-) (C57BL/6) recipients survived significantly longer (mean survival time, 38 +/- 8 days) compared with those transplanted into wild-type control mice. (10 +/- 2 days; P < 0.0001). Twenty percent of islet allografts in CCR5(-/-) animals without other treatment survived >90 days. In CCR5(-/-) mice, intragraft mRNA I expression of interleukin-4 and -5 was increased, whereas that of interferon-gamma was decreased, corresponding to a Th2 pattern of T-cell. activation in the target tissues compared with a Th1 pattern observed in controls. A similar Th2 response pattern I was also observed in the periphery (splenocytes responding to donor cells) by enzyme-linked immunosorbent spot assay. We conclude that CCR5 plays an important role in orchestrating the Th1 immune response leading to islet allograft rejection. Targeting this chemokine receptor, therefore, may provide a clinically useful strategy to prevent islet allograft rejection. C1 Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Div Renal, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Div Renal, 75 Francis St, Boston, MA 02115 USA. NR 30 TC 70 Z9 72 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2002 VL 51 IS 8 BP 2489 EP 2495 DI 10.2337/diabetes.51.8.2489 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579NZ UT WOS:000177185900020 PM 12145162 ER PT J AU Meigs, JB Larson, MG D'Agostino, RB Levy, D Clouse, ME Nathan, DM Wilson, PWF O'Donnell, CJ AF Meigs, JB Larson, MG D'Agostino, RB Levy, D Clouse, ME Nathan, DM Wilson, PWF O'Donnell, CJ TI Coronary artery calcification in type 2 diabetes and insulin resistance - The Framingham Offspring Study SO DIABETES CARE LA English DT Article; Proceedings Paper CT American-Heart-Association Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02, 2001 CL SAN ANTONIO, TEXAS SP Amer Heart Assoc ID BEAM COMPUTED-TOMOGRAPHY; PREDICT CARDIOVASCULAR RISK; INTIMAL-MEDIAL THICKNESS; CAROTID WALL THICKNESS; HEART-DISEASE; GLUCOSE-TOLERANCE; MYOCARDIAL-INFARCTION; NONDIABETIC SUBJECTS; PLASMA-GLUCOSE; ATHEROSCLEROSIS AB OBJECTIVE- To assess risk for subclinical coronary atherosclerosis using electron beam-computed tomography in subjects with or without insulin resistance and with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT/impaired fasting glucose [IFG]) or type 2 diabetes. RESEARCH DESIGN AND METHODS- We categorized glucose tolerance by type 2 diabetes therapy (diagnosed diabetes) or with an oral glucose tolerance test (OGTT) (IFG, IGT, and OGTT-detected diabetes) and insulin resistance as an elevated fasting insulin level, in subjects attending the fifth examination (1991-1995) of the Framingham Offspring Study. A representative subset of subjects without clinical atherosclerosis was selected for electron beam computed tomography in 1998-1999 from age- and sex-stratified quintiles of the Framingham risk score. The presence of subclinical atherosclerosis was defined as the upper quartile of the Agatston score distribution (score > 170). We assessed risk for subclinical atherosclerosis using multivariable logistic regression. RESULTS- Of 325 subjects aged 31-73 years, 51% were men, 11.2% had IFG/IGT, and 9.9% had diabetes (2.8% with diagnosed diabetes); 14.5% had insulin resistance. Compared with NGT, subjects with IFG/IGT tended to be more likely (adjusted odds ratio 1.5, 95% CI 0.7-3.4) and those with diabetes were significantly more likely (2.7, 1.2-6.1) to have subclinical coronary atherosclerosis. In age- and sex-adjusted models, subjects with insulin resistance were more likely to have subclinical atherosclerosis than those without insulin resistance (2.1, 1.01-4.2), but further risk factor adjustment weakened this association. In adjusted models including insulin resistance, diabetes remained associated with risk for subclinical atherosclerosis (2.8, 1.2-6.7); diagnosed diabetes (6.0, 1.4-25.2) had a larger effect than OGTT-detected diabetes (2.1, 0.8-5.5). CONCLUSIONS- Individuals with diabetes have an elevated burden of subclinical coronary atherosclerosis. Aggressive clinical atherosclerosis prevention is warranted, especially in diagnosed diabetes. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Dept Math Stat, Boston, MA 02215 USA. Boston Univ, Consulting Unit, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Boston Univ, Sch Med, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [N01-HC-38083] NR 43 TC 74 Z9 75 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 AUG PY 2002 VL 25 IS 8 BP 1313 EP 1319 DI 10.2337/diacare.25.8.1313 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UB UT WOS:000185504100008 PM 12145227 ER PT J AU Anderson, BJ Vangsness, L Connell, A Butler, D Goebel-Fabbri, A Laffel, LMB AF Anderson, BJ Vangsness, L Connell, A Butler, D Goebel-Fabbri, A Laffel, LMB TI Family conflict, adherence, and glycaemic control in youth with short duration Type 1 diabetes SO DIABETIC MEDICINE LA English DT Article; Proceedings Paper CT 61st Scientific Session of the American-Diabetes-Association CY JUN 22-26, 2001 CL PHILADELPHIA, PENNSYLVANIA SP Amer Diabetes Assoc DE Type 1 diabetes; family conflict; adherence; blood glucose monitoring; glycaemic control; parental involvement ID LONGITUDINAL FOLLOW-UP; METABOLIC CONTROL; GLYCEMIC CONTROL; GLYCOSYLATED HEMOGLOBIN; MELLITUS; ADOLESCENTS; CHILDREN; MANAGEMENT; PREDICTORS; CARE AB Aims Behavioural support around diabetes management tasks is linked to glycaemic outcomes. In this study we investigated the relationship between diabetes-related parental behaviours (conflict around and involvement in treatment tasks), adherence to blood glucose monitoring (BGM), and glycaemic control in youth with short duration Type 1 diabetes mellitus (DM). Methods In a cross-sectional study, 104 youth (aged 8-17 years, duration of Type 1 DM 0.5-6 years) along with a parent, completed the Diabetes Conflict Scale. Parental involvement in management tasks was assessed with structured interviews and the Diabetes Family Responsibility Questionnaire. Adherence to BGM was evaluated by family report and by independent clinician rating. Glycaemic control was assessed with glycosylated haemoglobin (HbA(1c)) (ref. range, 4-6%). Results Children (8-12 years; n = 69) and adolescents (13-17 years; n = 35), respectively, had similar durations of diabetes (x +/- SD; 2.7 +/- 1.69, 2.4 +/-.32 years) and similar glycaemic control (8.3 +/- 1.1%, 8.4 +/-.1%). In both age groups, parental involvement was a significant predictor of adherence to BGM (P = 0.01). Multivariate analyses, controlling for age, sex, disease duration, and BGM adherence, revealed that higher diabetes conflict significantly related to poorer glycaemic control (HbA(1c)) (R-2 = 0.17; P < .01). Conclusions These findings indicate that in this cohort, early in the course of diabetes, diabetes-specific conflict and adherence to BGM became strongly linked to the child's glycaemic control. This suggests that to insure optimal control, it may be beneficial to introduce targeted interventions to build positive family involvement and interaction around diabetes tasks early in the disease course, before negative behaviours become established. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Paediat Unit,Behav Res & Mental Hlth Sect, Boston, MA 02115 USA. RP Anderson, BJ (reprint author), Joslin Diabet Ctr, Behav & Mental Hlth Sect, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 46887, R01 DK046887] NR 41 TC 159 Z9 160 U1 2 U2 9 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD AUG PY 2002 VL 19 IS 8 BP 635 EP 642 AR UNSP DME_752.fm DI 10.1046/j.1464-5491.2002.00752.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579WB UT WOS:000177199800004 PM 12147143 ER PT J AU Bril, V Perkins, BA AF Bril, V Perkins, BA TI Comparison of vibration perception thresholds obtained with the Neurothesiometer and the CASE IV and relationship to nerve conduction studies SO DIABETIC MEDICINE LA English DT Article DE vibration perception threshold; quantitative sensory threshold; comparison; diabetic neuropathy ID DIABETIC NEUROPATHY; PERIPHERAL NEUROPATHY; BIOTHESIOMETER; POLYNEUROPATHY; TESTS AB Aims Vibration perception thresholds (VPTs) are used frequently to assess somatosensory pathways in clinical trials. Different equipment, testing paradigms, and stimulation sites produce varying results which make comparisons between trials and patient populations challenging. Information comparing the VPT obtained with the Neurothesiometer with that with the Vibratron is available, but not for a similar comparison with the CASE IV (computer-assisted sensory examination device). Methods Subjects (n = 478) including reference, non-neuropathic subjects with diabetes mellitus (DM), and diabetic patients with mild, moderate and severe diabetic sensorimotor polyneuropathy (DSP) had VPTs measured with the CASE IV and Neurothesiometer, as well as standard sural nerve conduction studies (NCS), all performed during the same half-day. The dorsum of the foot was used as the site of stimulation for the CASE IV VPT determination and the distal phalanx of the first toe for the Neurothesiometer. Results VPTs by the CASE IV and the Neurothesiometer compared moderately by linear regression analyses (R-2 = 0.547, P < 0.0001), and by 95% confidence intervals. Sensitivity for the diagnosis of mild DSP was 70% with the Neurothesiometer and 49% with the CASE IV. VPTs determined by either the Neurothesiometer or the CASE IV correlated with similar agreement to the sural nerve action potential amplitude as determined by nerve conduction studies (NCS) (R-2 = 0.456 and 0.461, respectively, P < 0.0001). Conclusions The results demonstrated a significant correlation of VPT values in different stages of DSP obtained by the two methods. The Neurothesiometer was more sensitive for the diagnosis of DSP, particularly in those with mild neuropathy. Similar correlations between VPTs and electrophysiological parameters were observed, indicating that both methods are valid, and thus the Neurothesiometer may be preferable due to the ease and rapidity of testing by this method. C1 Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 2C4, Canada. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Bril, V (reprint author), Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, EN 11-209,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. NR 21 TC 26 Z9 27 U1 1 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD AUG PY 2002 VL 19 IS 8 BP 661 EP 666 AR UNSP DME_759.fm DI 10.1046/j.1464-5491.2002.00759.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 579WB UT WOS:000177199800008 PM 12147147 ER PT J AU Kulkarni, RN Chalkey, K Garcia, L Kahn, R Magnuson, M Holzenberger, M AF Kulkarni, RN Chalkey, K Garcia, L Kahn, R Magnuson, M Holzenberger, M TI beta-cell-specific double knockout of the insulin- and IGF-1-receptors leads to severe early-onset diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 38th EASD Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 01-05, 2002 CL BUDAPEST, HUNGARY SP European Assoc Study Diabetes (EASD) C1 INSERM U515, Paris, France. Vanderbilt Univ, Nashville, TN USA. Joslin Diabet Ctr, Res Dept, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2002 VL 45 SU 2 MA 85 BP A31 EP A31 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 590HM UT WOS:000177813600086 ER PT J AU Lipsky, BA Driver, VR Edmiston, CE Thomas, J Wage, JM AF Lipsky, BA Driver, VR Edmiston, CE Thomas, J Wage, JM TI Delivering antibiotics to the lower limb by localized venous perfusion with a novel catheter device SO DIABETOLOGIA LA English DT Meeting Abstract CT 38th EASD Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 01-05, 2002 CL BUDAPEST, HUNGARY SP European Assoc Study Diabetes (EASD) C1 Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. Madigan Army Med Ctr, Tacoma, WA 98431 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. PharmaSpec Corp, Clin Affairs, Redmond, WA USA. PharmaSpec Corp, Regulatory Affairs, Redmond, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2002 VL 45 SU 2 MA 1061 BP A343 EP A343 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 590HM UT WOS:000177813601059 ER PT J AU Makhlouf, L Yamada, A Abdi, R Khuong, CQ Winn, HJ Auchincloss, H Sayegh, MH AF Makhlouf, L Yamada, A Abdi, R Khuong, CQ Winn, HJ Auchincloss, H Sayegh, MH TI Distinct roles of direct and indirect allorecognition pathways in islet allograft rejection in autoimmune and non-autoimmune recipients SO DIABETOLOGIA LA English DT Meeting Abstract CT 38th EASD Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 01-05, 2002 CL BUDAPEST, HUNGARY SP European Assoc Study Diabetes (EASD) C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2002 VL 45 SU 2 MA 208 BP A71 EP A71 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 590HM UT WOS:000177813600209 ER PT J AU Menzaghi, C Ercolino, T Di Paola, R Berg, AH Warram, JH Scherer, PE Trischitta, V Doria, A AF Menzaghi, C Ercolino, T Di Paola, R Berg, AH Warram, JH Scherer, PE Trischitta, V Doria, A TI A haplotype at the adiponectin locus is associated with obesity and other features of the insulin-resistance syndrome SO DIABETOLOGIA LA English DT Meeting Abstract CT 38th EASD Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 01-05, 2002 CL BUDAPEST, HUNGARY SP European Assoc Study Diabetes (EASD) C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA USA. Albert Einstein Coll Med, Cell Biol & Diabet Res & Training Ctr, Bronx, NY 10467 USA. Res Inst Casa Sollievo Sofferenza, Res Unit Endocrinol, San Giovanni Rotondo, Italy. RI Di Paola, Rosa/G-7813-2011; Trischitta, Vincenzo/K-1487-2016 OI Di Paola, Rosa/0000-0001-5837-9111; Trischitta, Vincenzo/0000-0003-1174-127X NR 0 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2002 VL 45 SU 2 MA 161 BP A56 EP A56 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 590HM UT WOS:000177813600162 ER PT J AU Monzillo, LU Caballero, E Yohai, F Villar, NGP Romero, A Lerman, I Herrera-Acena, G AF Monzillo, LU Caballero, E Yohai, F Villar, NGP Romero, A Lerman, I Herrera-Acena, G TI The short and long term effect of a non-traditional culturally oriented diabetes education program on the metabolic control of Hispanics patients with Type 2 diabetes. SO DIABETOLOGIA LA English DT Meeting Abstract CT 38th EASD Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 01-05, 2002 CL BUDAPEST, HUNGARY SP European Assoc Study Diabetes (EASD) C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2002 VL 45 SU 2 MA 978 BP A317 EP A317 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 590HM UT WOS:000177813600976 ER PT J AU Sadagursky, M Sizyakov, G White, MF Kadowaki, T Wertheimer, E AF Sadagursky, M Sizyakov, G White, MF Kadowaki, T Wertheimer, E TI IRS1 and IRS2 have distinct roles in primary skin keratinocytes and skin fibroblasts SO DIABETOLOGIA LA English DT Meeting Abstract CT 38th EASD Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 01-05, 2002 CL BUDAPEST, HUNGARY SP European Assoc Study Diabetes (EASD) C1 Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Tokyo, Grad Sch Med, Dept Internal Med, Tokyo 1130033, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2002 VL 45 SU 2 MA 127 BP A45 EP A45 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 590HM UT WOS:000177813600128 ER PT J AU Wertheimer, E Takeda, J Tennenbaum, T Kahn, CR Sizyakov, G AF Wertheimer, E Takeda, J Tennenbaum, T Kahn, CR Sizyakov, G TI SIRKO - The skin specific insulin receptor knockout mouse SO DIABETOLOGIA LA English DT Meeting Abstract CT 38th EASD Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 01-05, 2002 CL BUDAPEST, HUNGARY SP European Assoc Study Diabetes (EASD) C1 Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Osaka Univ, Sch Med, Osaka, Japan. Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2002 VL 45 SU 2 MA 1 BP A3 EP A3 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 590HM UT WOS:000177813600002 ER PT J AU Brady, KT Myrick, H Henderson, S Coffey, SF AF Brady, KT Myrick, H Henderson, S Coffey, SF TI The use of divalproex in alcohol relapse prevention: a pilot study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE divalproex; alcoholism; withdrawal; hostility; irritability ID DOUBLE-BLIND; GABAPENTIN TREATMENT; CONTROLLED TRIAL; SUBSTANCE USE; DEPENDENCE; WITHDRAWAL; CARBAMAZEPINE; PHARMACOTHERAPY; FLUOXETINE; VALPROATE AB Anticonvulsant agents show promise in the treatment of the acute symptoms of alcohol withdrawal and may also treat some symptoms associated with the protracted abstinence syndrome. Impulsivity, hostility and irritability are common characteristics of alcohol-dependent individuals, and there is some evidence that anticonvulsant agents decrease these traits in individuals with a number of different psychiatric disorders. This pilot study is a 12-week, double-blind, placebo-controlled trial of an anticonvulsant agent, divalproex (DVPX), in alcohol-dependent individuals. Alcohol use (Timeline Follow Back), impulsivity (Barratt Impulsivity Scale), irritability and aggression (Buss-Durkee Hostility Index; and Anger, Irritability, Aggression Scale) were measured at baseline and throughout the 12-week treatment period. Drinking decreased significantly in both the placebo and the DVPX-treated groups. In the DVPX group, a significantly smaller percentage of individuals relapsed to heavy drinking, but there were no significant differences in other alcohol-related outcomes. There were significantly greater decreases in irritability in the DVPX-treated group and a trend towards greater decreases on measures of lability and verbal assault. There were no significant between-group differences on measures of impulsivity. While DVPX did not have a robust effect on alcohol-related outcomes, it did have modest impact on a measure of irritability. This is consistent with the findings of other investigators exploring the use of DVPX in schizophrenia, personality disorder and a number of other psychiatric disorders. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Med Univ S Carolina, Ctr Drugs & Alcohol Programs, Inst Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. SUNY Buffalo, Buffalo Gen Hosp, Dept Psychiat, Buffalo, NY 14203 USA. RP Brady, KT (reprint author), Med Univ S Carolina, Ctr Drugs & Alcohol Programs, Inst Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. NR 42 TC 66 Z9 67 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 1 PY 2002 VL 67 IS 3 BP 323 EP 330 AR PII S0376-8716(02)00105-9 DI 10.1016/S0376-8716(02)00105-9 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 580EC UT WOS:000177221200011 PM 12127203 ER PT J AU Rosen, MI Rosenheck, RA Shaner, AL Eckman, TA Gamache, GR Krebs, CW AF Rosen, MI Rosenheck, RA Shaner, AL Eckman, TA Gamache, GR Krebs, CW TI Substance abuse and the need for money management assistance among psychiatric inpatients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE payee; case management; dual diagnosis; substance abuse; social services AB Patients who mismanage their funds may benefit from financial advice, case management or the involuntary assignment of a payee who restricts direct access to funds. Data from a survey of psychiatric inpatients at four VA hospitals (N = 236) was used to evaluate the relationship between substance abuse and clinician-rated need for money management assistance. Multivariate analytic techniques were used to control for sociodemographic factors and psychopathology. Alcohol and drug use severity both were modestly associated with need for assistance. The effect of substance use severity was greater in patients who were also diagnosed with a major mental illness. Clinicians indicated that 27 patients (11% of the sample) required an involuntary payee and 21 of the 27 (78%) had a Substance Abuse diagnosis. Only drug use severity was significantly associated with need for a payee. These data describe a substantial unmet need for money management assistance in psychiatric inpatients, particularly among those with substance abuse disorders. There is a need to examine the process by which the Social Security and Veterans Benefits Administrations assign payees to determine whether patients with co-morbid substance abuse are not being assigned a payee in spite of their discernible need for one. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 VA Connecticut Healthcare Syst, Dept Psychiat 116A, West Haven, CT 06516 USA. W Los Angeles Vet Affairs Med Ctr, Dept Mental Hlth, Los Angeles, CA 90073 USA. Northampton VA Med Ctr, Mental Illness Res Educ & Clin Care Ctr, Leeds, MA 01053 USA. VA Bedford Med Ctr, Mental Illness Res Educ & Clin Care Ctr, Bedford, MA 01730 USA. RP Rosen, MI (reprint author), VA Connecticut Healthcare Syst, Dept Psychiat 116A, Bldg 1,Rm 953-M,950 Campbell Ave, West Haven, CT 06516 USA. FU NIDA NIH HHS [R01-DA12952, P50-DA09241] NR 8 TC 17 Z9 17 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 1 PY 2002 VL 67 IS 3 BP 331 EP 334 AR PII S0376-8716(02)00080-7 DI 10.1016/S0376-8716(02)00080-7 PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 580EC UT WOS:000177221200012 PM 12127204 ER PT J AU Chen, JF Schwarzschild, MA AF Chen, JF Schwarzschild, MA TI A(2A) adenosine receptors in the CNS and Parkinson's disease: Insights from the A(2A) receptor knockout mouse model SO DRUG DEVELOPMENT RESEARCH LA English DT Meeting Abstract CT 7th International Symposium on Adenosine and Adenine Nucleotides CY MAY, 2001 CL GOLD COAST, AUSTRALIA SP Abbott Labs, Adenosine Therapeut, Bank Leumi, Biogen, CV Therapeut, Euroscreen, Fjisawa Healthcare Inc, GlaxoSmithKline, Griffith Univ, Inspire Pharmaceut Inc, Johnson & Johnson, King Medco Res Inc, Kyowa Hakko, Merck, Novartis, Pfizer C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD AUG PY 2002 VL 56 IS 4 MA 14 BP 549 EP 549 PG 1 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 611VJ UT WOS:000179038200016 ER PT J AU Larson, VD Williams, DW Henderson, WG Luethke, LE Beck, LB Noffsinger, D Bratt, GW Dobie, RA Fausti, SA Haskell, GB Rappaport, BZ Shanks, JE Wilson, RH AF Larson, VD Williams, DW Henderson, WG Luethke, LE Beck, LB Noffsinger, D Bratt, GW Dobie, RA Fausti, SA Haskell, GB Rappaport, BZ Shanks, JE Wilson, RH TI A multi-center, double blind clinical trial comparing benefit from three commonly used hearing aid circuits SO EAR AND HEARING LA English DT Article AB Objective: Although numerous studies have demonstrated that hearing aids provide significant benefit, carefully controlled, multi-center clinical trials have not been conducted. A multi-center clinical trial was conducted to compare the efficacy of three commonly used hearing aid circuits: peak clipping, compression limiting, and wide dynamic range compression. Conclusions: The three hearing aid circuits studied provide significant benefit both in quiet and in noisy listening situations. The two compression hearing aids appear to provide superior benefits compared to the linear circuit, although the differences between the hearing aids were smaller than the differences between unaided and aided conditions. Design: Patients (N = 360) with bilateral, sensorineural hearing loss were studied using a double blind, three-period, three-treatment crossover design. The patients were fit with each of three programmable hearing aid circuits. Outcome tests were administered in the unaided condition at baseline and then after 3 mo usage of each circuit, the tests were administered in both aided and unaided conditions. The outcome test battery included tests of speech recognition, sound quality and subjective scales of hearing aid benefit, including patients' overall rank-order rating of the three circuits. Results: Each hearing aid circuit improved speech recognition markedly, with greater improvement observed for soft and conversationally loud speech in both quiet and noisy listening conditions. In addition, a significant reduction in the problems encountered in communication was observed. Some tests suggested that the two compression hearing aids provided a better listening experience than the peak clipping hearing aid. In the rank-order ratings, patients preferred the compression limiting hearing aid more frequently than the other two hearing aids. Conclusions: The three hearing aid circuits studied provide significant benefit both in quiet and in noisy listening situations. The two compression hearing aids appear to provide superior benefits compared to the linear circuit, although the differences between the hearing aids were smaller than the differences between unaided and aided conditions. C1 Howard Leight Ind, San Diego, CA 92154 USA. Hines VA Cooperat Studies Program Coordinating Ct, Hines, IL USA. Natl Inst Deafness & Other Commun Dis, Bethesda, MD USA. Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Dept Vet Affairs Med Ctr, Washington, DC USA. Dept Vet Affairs Med Ctr, Nashville, TN USA. Dept Vet Affairs Med Ctr, Portland, OR USA. Dept Vet Affairs Med Ctr, Iowa City, IA USA. Dept Vet Affairs Med Ctr, Albuquerque, NM USA. Dept Vet Affairs Med Ctr, Long Beach, CA USA. Dept Vet Affairs Med Ctr, Mountain Home, TN USA. RP Larson, VD (reprint author), Howard Leight Ind, 7828 Waterville Rd, San Diego, CA 92154 USA. OI dobie, robert/0000-0003-3833-1772 NR 22 TC 20 Z9 22 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD AUG PY 2002 VL 23 IS 4 BP 269 EP 276 DI 10.1097/01.AUD.0000027409.90397.E4 PG 8 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 586CN UT WOS:000177566400001 PM 12195168 ER PT J AU Noffsinger, D Haskell, GB Larson, VD Williams, DW Wilson, E Plunkett, S Kenworthy, D AF Noffsinger, D Haskell, GB Larson, VD Williams, DW Wilson, E Plunkett, S Kenworthy, D TI Quality rating test of hearing aid benefit in the NIDCD/VA Clinical Trial SO EAR AND HEARING LA English DT Article ID SPEECH-INTELLIGIBILITY; SUBJECTIVE JUDGMENTS; COMPRESSION; LOUDNESS; CIRCUITS; STIMULI; CLARITY AB Objective: As part of a large clinical trial that compared three hearing aid circuits using several evaluation methods, judgments about quality of listening experiences were sought from all subjects. Three dimensions were examined: loudness, noise interference and overall liking (quality). Design: Eight Audiology units in VA Medical Centers participated. Three hearing aid circuits were compared: linear peak clipper, compression limiter, and wide dynamic range compressor. The experimental design was a three-period, three-treatment crossover design. Baseline measures were made using a battery of tests in unaided conditions. Subjects (N = 360) were then stratified by participating site and randomized to one of six sequences of the three hearing aid circuits. Each circuit was fit bin-aurally and all subjects used each of the three circuits for 3 mo. All outcome measures were administered in unaided and aided conditions after each 3-mo period. The study used a double-blind strategy, i.e., neither the audiologist giving the tests nor the subject, knew which circuit was being used. A different audiologist programmed the devices. Results: For loudness judgments, soft and loud presentations of speech in quiet and in babble competition were judged more comfortable via the wide dynamic range circuit. The noise interference tasks and overall liking of the listening experience showed few significant differences across circuits. All circuits made the listening experience more comfortably loud for soft and conversation-level speech. Conclusions. Differences across circuits in terms of the overall quality of the listening experience and how noise interference was rated were small. Only isolated conditions, usually favoring the WDRC circuit, reached significance levels. The loudness dimension results were clearer. The WDRC circuit made sounds at either the loud or soft extreme more comfortable. When subjects were grouped by amount and configuration of hearing loss, the advantages for the WDRC and to a lesser extent the linear compression-limited circuit were clearest among subjects with mild hearing losses with a >10 dB/octave high-frequency drop, and those with moderate, relatively flat hearing losses. C1 VA Greater Los Angeles Htlh Care Syst, Los Angeles, CA 90073 USA. VA Hines Cooperat Studies Program, Hines, IL USA. VA Med Ctr, Iowa City, IA USA. VA Med Ctr, Washington, DC USA. VA Med Ctr, Los Angeles, CA USA. RP Noffsinger, D (reprint author), VA Greater Los Angeles Htlh Care Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 28 TC 5 Z9 5 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD AUG PY 2002 VL 23 IS 4 BP 291 EP 300 DI 10.1097/01.AUD.0000027410.88315.D0 PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 586CN UT WOS:000177566400004 PM 12195171 ER PT J AU Haskell, GB Noffsinger, D Larson, VD Williams, DW Dobie, RA Rogers, JL AF Haskell, GB Noffsinger, D Larson, VD Williams, DW Dobie, RA Rogers, JL TI Subjective measures of hearing aid benefit in the NIDCD/VA Clinical Trial SO EAR AND HEARING LA English DT Article AB Objective. Subjective measures of performance were assessed on three different hearing aid circuits as part of a large clinical trial. These measurements included the Profile of Hearing Aid Performance and a subjective ranking of individual preference. Design: A multi-center, double-masked clinical trial of hearing aids was conducted at eight VA Medical Centers. Three hearing aid circuits, a linear peak-clipper, a linear compression limiter and a wide dynamic range compressor, were investigated. The experimental design was a three-period, three-treatment crossover design. Subjects (N = 360) were stratified by site and randomized to one of six sequences for the hearing aid circuits. All fittings were binaural and involved a 3-mo trial with each of the three circuits. All subjective measures were administered for unaided and aided conditions at the end of each trial period. Results: While all of the circuits resulted in improved scores on the aided versus the unaided PHAP, there were few conditions in which one circuit outperformed the others. An exception was the aversiveness of sound subscale where the peak clipper frequently scored worse than either the compression limiter or the wide dynamic range compressor. In the subjective ranking scale the compression limiter received more first place rankings than the other two circuits, especially for one subgroup of patients with moderate flat hearing loss. Conclusions: All circuits were perceived as beneficial by these subjects in most situations. The peak clipper scored worse on aversiveness of sound than did the other two circuits for most subjects, while the compression limiter seemed to have a slight advantage in subjective rankings. Most subjects perceived considerable aided benefit in situations involving background noise and reverberation, situations where hearing aid benefit is often questioned. C1 VA Med Ctr, Iowa City, IA USA. VA Med Ctr, Washington, DC USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Howard Leight Ind, San Diego, CA USA. VA Hines Cooperat Studies Program Coordinating Ct, Hines, IL USA. NIDCD, NIH, Bethesda, MD USA. RP Haskell, GB (reprint author), 8501 E Alameda Ave,Apt 1328, Denver, CO 80230 USA. OI dobie, robert/0000-0003-3833-1772 NR 5 TC 9 Z9 14 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD AUG PY 2002 VL 23 IS 4 BP 301 EP 307 DI 10.1097/01.AUD.0000027404.26058.47 PG 7 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 586CN UT WOS:000177566400005 PM 12195172 ER PT J AU Chia, KKM Picard, MH Skopicki, HA Hung, J AF Chia, KKM Picard, MH Skopicki, HA Hung, J TI Viability of hypokinetic segments: Influence of tethering from adjacent segments SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE viability; hypokinesis; tethering; dobutamine ID CORONARY-ARTERY DISEASE; MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; EMISSION COMPUTED-TOMOGRAPHY; LEFT-VENTRICULAR DYSFUNCTION; HIBERNATING MYOCARDIUM; WALL-MOTION; PREDICTING RECOVERY; HEART-DISEASE AB Hypokinetic myocardium is presumed to be reversibly dysfunctional. However, hypokinetic segments do not necessarily improve after revascularization since their outcome can be influenced by tethering effects of adjacent myocardium. To assess whether hypokinetic segments improve following revascularization, 24 patients underwent resting and dobutamine stress echocardiography (DSE), with a total of 420 (20 per patient) myocardial segments studied pre- and postrevascularization. One hundred fifty-five hypokinetic segments were identified prerevascularization. wwPostrevascularization, only 57% of these segments improved in wall motion, while 43% showed no improvement or worsening of wall motion. Low dose (5-10 mug/kg/min) DSE identified correctly 57 (65%) of 88 segments that improved, and falsely predicted improvement in 26 (39010) of 67 segments that ultimately did not improve postrevascularization. Of the hypokinetic segments that did not improve, 90% were adjacent to at least one severely hypokinetic or akinetic segment as compared with 73% of the segments that improved following revascularization (P = 0.009). Sixty-five percent of all true positive DSE responses were adjacent to at least one akinetic or severely hypokinetic segment, while 87% of all false negative DSE responses were adjacent to at least one akinetic or severely hypokinetic segment (P = 0.03). In conclusion, myocardial segments found to be hypokinetic do not necessarily improve after revascularization. This may be related to tethering influences of adjacent segments, which have a contrasting level of function. C1 Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Cardiac Ultrasound Lab, VBK 508, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 29 TC 7 Z9 8 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD AUG PY 2002 VL 19 IS 6 BP 475 EP 481 DI 10.1046/j.1540-8175.2002.00475.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 593FQ UT WOS:000177980700005 PM 12356342 ER PT J AU Watson, PA Vinson, C Nesterova, A Reusch, JEB AF Watson, PA Vinson, C Nesterova, A Reusch, JEB TI Content and activity of cAMP response element-binding protein regulate platelet-derived growth factor receptor-alpha content in vascular smooth muscles SO ENDOCRINOLOGY LA English DT Article ID CELL-PROLIFERATION; TRANSCRIPTIONAL REGULATION; GENE-EXPRESSION; PPAR-GAMMA; MIGRATION; PDGF; DELTA; ATHEROSCLEROSIS; TROGLITAZONE; RATS AB Experiments in vascular smooth muscle cells (SMCs) indicate that the transcription factor cAMP response element-binding protein (CREB), the cyclic nucleotide response element-binding protein, suppresses expression of the platelet-derived growth factor-a receptor gene (PDGFRalpha). Adenovirus-mediated expression of constitutively active CREB mutants decreases PDGFRalpha mRNA, PDGFRalpha protein, and PDGFRalpha promoter-luciferase reporter activity in cultured SMCs. Expression of dominant negative CREB protein, A-CREB, increases PDGFRalpha protein content and the PDGFRalpha-promoter activity in SMCs. Active CREB prevents activation of PDGFRalpha promoter-luciferase reporter activity by CCAAT/enhancer-binding protein-delta (C/EBPdelta), shown to mediate IL-1beta stimulation of PDGFRalpha expression. Exposure of cultured SMCs to high glucose or reactive oxidant stress, which decrease CREB protein content and activity, increases PDGFRalpha protein content and promoter activity. Expression of active CREB blunts reactive oxidant stress-induced PDGFRalpha accumulation in SMCs. Loss of CREB protein in aortic walls of rats with streptozotocin-induced diabetes is accompanied by an increase in PDGFRalpha content. In Ob/Ob mice (which demonstrate reduced aortic wall CREB content vs. Ob/- controls), treatment with the peroxisomal proliferator-activated receptor gamma rosiglitazone increases CREB content and decreases PDGFRalpha content in the aortic wall. Thus, both in vitro and in vivo loss of CREB content and activity and subsequent accumulation of PDGFRalpha may contribute to SMC activation during diabetes. C1 Denver VA Med Ctr, Denver Res Inst, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Endocrinol, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80220 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Reusch, JEB (reprint author), Denver VA Med Ctr, Denver Res Inst, Room 9C-120,1055 Clermont St, Denver, CO 80220 USA. NR 22 TC 14 Z9 14 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 AUG PY 2002 VL 143 IS 8 BP 2922 EP 2929 DI 10.1210/en.143.8.2922 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 576JC UT WOS:000176999600013 PM 12130557 ER PT J AU Hsieh, TJ Mang, SL Filep, JG Tang, SS Ingelfinger, JR Chan, JSD AF Hsieh, TJ Mang, SL Filep, JG Tang, SS Ingelfinger, JR Chan, JSD TI High glucose stimulates angiotensinogen gene expression via reactive oxygen species generation in rat kidney proximal tubular cells SO ENDOCRINOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; DIABETIC NEPHROPATHY; MESANGIAL CELLS; MESSENGER-RNA; TGF-BETA; CELLULAR HYPERTROPHY; MOLECULAR MECHANISMS; OXIDATIVE STRESS; TRANSCRIPTION; PATHWAYS AB The present studies investigated whether the effect of high glucose levels on angiotensinogen (ANG) gene expression in kidney proximal tubular cells is mediated via reactive oxygen species (ROS) generation and p38 MAPK activation. Rat immortalized renal proximal tubular cells (IRPTCs) were cultured in monolayer. Cellular ROS generation and p38 MAPK phosphorylation were assessed by lucigenin assay and Western blot analysis, respectively. The levels of immunoreactive rat ANG secreted into the media and cellular ANG mRNA were determined by a specific RIA and RT-PCR, respectively. High glucose (25 mm) evoked ROS generation and p38 MAPK phosphorylation as well as stimulated immunoreactive rat ANG secretion and ANG mRNA expression in IRPTCs. These effects of high glucose were blocked by antioxidants (taurine and tiron), inhibitors of mitochondrial electron transport chain complex I (rotenone) and II (thenoyltrifluoroacetone), an inhibitor of glycolysis-derived pyruvate transport into mitochondria (alpha-cyano-4-hydroxycinnamic acid), an uncoupler of oxidative phosphorylation (carbonyl cyanide m-chlorophenylhydrazone), a manganese superoxide dismutase mimetic, catalase, and a specific inhibitor of p38 MAPK (SB 203580), but were not affected by an inhibitor of the malate-aspartate shuttle (aminooxyacetate acid). Hydrogen peroxide (greater than or equal to 10(-5) m) also stimulated p38 MAPK phosphorylation, ANG secretion, and ANG mRNA gene expression, but its stimulatory effect was blocked by catalase and SB 203580. These studies demonstrate that the stimulatory action of high glucose on ANG gene expression in IRPTCs is mediated at least in part via ROS generation and subsequent p38 MAPK activation. C1 Univ Montreal, CHU Montpellier, Hop Hotel Dieu, Res Ctr, Montreal, PQ H2W 1T8, Canada. Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ H1T 2M4, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Chan, JSD (reprint author), Univ Montreal, CHU Montpellier, Hop Hotel Dieu, 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 56 TC 125 Z9 131 U1 1 U2 9 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 AUG PY 2002 VL 143 IS 8 BP 2975 EP 2985 DI 10.1210/en.143.8.2975 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 576JC UT WOS:000176999600019 PM 12130563 ER PT J AU Abraham, EJ Leech, CA Lin, JC Zulewski, H Habener, JF AF Abraham, EJ Leech, CA Lin, JC Zulewski, H Habener, JF TI Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells SO ENDOCRINOLOGY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; HOMEODOMAIN PROTEIN IDX-1; ENDOCRINE PANCREAS; GENE-EXPRESSION; BETA-CELLS; STEM-CELLS; RESPONSE ELEMENT; SECRETING CELLS; AR42J CELLS; TRANSCRIPTION AB Glucagon-like peptide-1 (GLP-1) is an intestinal incretin hormone, derived from the processing of proglucagon, that exerts insulinotropic actions on insulin-producing pancreatic islet beta-cells. Recently GLP-1 was shown to stimulate the growth and differentiation (neogenesis) of beta-cells and appears to do so by inducing the expression of the homeodomain protein IDX-1 (islet duodenum homeobox-1; also known as PDX-1, pancreatic and duodenal homeobox gene; and as IPF-1, insulin promoter factor), which is required for pancreas development and the expression of beta-cell-specifie genes. Earlier we identified multipotential progenitor cells in the islet and ducts of the pancreas, termed nestin-positive islet-derived progenitor cells (NIPs). Here we report the expression of functional GLP-1 receptors on NIPs and that GLP-1 stimulates the differentiation of NIPs into insulin-producing cells. Furthermore, confluent NIP cultures express the proglucagon gene and secrete GLP-1. These findings suggest a model of islet development in which pancreatic progenitor cells express both GLP-1 receptors and proglucagon with the formation of GLP-1. Locally produced GLP-1 may act as an autocrine/paracrine developmental morphogen on receptors on NIPs, resulting in the activation of IDX-1 and the expression of the proinsulin gene conferring a beta-cell phenotype. GLP-1 may be an important morphogen both for the embryonic development of the pancreas and for the neogenesis of beta-cells in the islets of the adult pancreas. C1 Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, 55 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01 DK 55365, R01 DK 30834] NR 50 TC 222 Z9 254 U1 1 U2 10 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2002 VL 143 IS 8 BP 3152 EP 3161 DI 10.1210/en.143.8.3152 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 576JC UT WOS:000176999600037 PM 12130581 ER PT J AU Suzuki, T Morita, R Sugimoto, Y Sugawara, T Bai, DS Alonso, ME Medina, MT Bailey, JN Rasmussen, A Ramos-Peek, J Cordova, S Donnadieu, FR Ochoa, A Jara-Prado, A Inazawa, J Delgado-Escueta, AV Yamakawa, K AF Suzuki, T Morita, R Sugimoto, Y Sugawara, T Bai, DS Alonso, ME Medina, MT Bailey, JN Rasmussen, A Ramos-Peek, J Cordova, S Donnadieu, FR Ochoa, A Jara-Prado, A Inazawa, J Delgado-Escueta, AV Yamakawa, K TI Identification and mutational analysis of candidate genes for juvenile myoclonic epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5 SO EPILEPSY RESEARCH LA English DT Article DE leucine-rich repeat-containing 1 gene; juvenile myoclonic epilepsy; EJM1 ID POTASSIUM CHANNEL GENE; GENERALIZED EPILEPSY; SUSCEPTIBILITY LOCUS; FEBRILE SEIZURES; CHROMOSOME-6; LINKAGE; PROTEIN; HETEROGENEITY; LOCALIZATION; FAMILIES AB Juvenile myoclonic epilepsy (JME) is one of the most frequent hereditary epilepsies characterized by myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Genetic studies have revealed four major chromosomal loci on 6p21.3, 6p11-12 6q24, and 15q14 as candidate regions harboring genes responsible for JME. Previously we reported the region on 6p11-p12 (EJM1), and here we report the identification and mutational analysis of candidate genes for EJM1. One of those is a leucine-rich repeat-containing I (LRRC1) gene that is composed of 14 exons and codes for 524 amino acid residues. In Northern analysis. 7 kb transcripts of LRRC1 gene were detected in multiple tissues, most strongly, in heart, lung. and kidney, Mutation analysis of LRRC1 gene in 20 JME patients from ten families revealed one nucleotide substitution that lead to amino acid exchange (c.577 A > G Ile193Val). This variation, however, did not co-segregate with the disease phenotype. We further performed mutational analyses of CLIC5, KIAA0057 and GCLC genes in or flank tot lie EJM1 region. These analyses did not provide an evidences that these genes are responsible for the JME phenotype. and suggested that these may not be the EJM1 gene. (C) Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Comprehens Epilepsy Program, Epilepsy Genet Genom Labs, Los Angeles, CA 90073 USA. VA GLAHS W Los Angeles, Los Angeles, CA 90073 USA. Natl Inst Neurol & Neurosurg, Mexico City, DF, Mexico. RIKEN, Inst Phys & Chem Res, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 3510198, Japan. Natl Autonomous Univ, Tegucigalpa, Honduras. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Cytogenet, Tokyo, Japan. RP Delgado-Escueta, AV (reprint author), Univ Calif Los Angeles, Sch Med, Comprehens Epilepsy Program, Epilepsy Genet Genom Labs, Room 3405 127B,Bldg 500,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Yamakawa, Kazuhiro/N-5050-2015; Rasmussen, Astrid/A-4878-2013 OI Rasmussen, Astrid/0000-0001-7744-2948 NR 25 TC 10 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD AUG PY 2002 VL 50 IS 3 BP 265 EP 275 AR PII S0920-1211(02)00052-9 DI 10.1016/S0920-1211(02)00052-9 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 593AY UT WOS:000177970100005 PM 12200217 ER PT J AU Mehta, RH Manfredini, R Hassan, F Bossone, E Cooper, JV Nienaber, C Isselbacher, EM Eagle, KA AF Mehta, RH Manfredini, R Hassan, F Bossone, E Cooper, JV Nienaber, C Isselbacher, EM Eagle, KA CA IRAD TI Seasonal variation in the risk of acute aortic dissections SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 31-SEP 04, 2002 CL BERLIN, GERMANY SP European Soc Cardiol C1 Univ Michigan, Dept Cardiol, Ann Arbor, MI 48109 USA. Univ Ferrara, Dept Internal Med & Hypertens 1, I-44100 Ferrara, Italy. Univ Rostock, Div Cardiol, Rostock, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2002 VL 23 SU S BP 10 EP 10 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 624HB UT WOS:000179753300031 ER PT J AU Dominguez, H Rask-Madsen, CRMC Ihlemann, NIN Hermann, THT Kober, LKL Torp-Pedersen, CTPC AF Dominguez, H Rask-Madsen, CRMC Ihlemann, NIN Hermann, THT Kober, LKL Torp-Pedersen, CTPC TI Tumor necrosis factor-alpha impairs insulin-stimulated endothelium-dependent vasodilatation and glucose uptake in humans SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 31-SEP 04, 2002 CL BERLIN, GERMANY SP European Soc Cardiol C1 KAS Gentofte, Cardiol P, Hellerup, Denmark. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. Rigshosp, Cardiol Lab B, DK-2100 Copenhagen, Denmark. OI DOMINGUEZ, HELENA/0000-0002-7089-2636 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2002 VL 23 SU S BP 169 EP 169 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 624HB UT WOS:000179753300636 ER PT J AU Friedrich, EB Sinha, S Li, L Dedhar, S Force, T Rosenzweig, A Gerszten, RE AF Friedrich, EB Sinha, S Li, L Dedhar, S Force, T Rosenzweig, A Gerszten, RE TI Role for a novel integrin linked kinase in leukocyte recruitment SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 31-SEP 04, 2002 CL BERLIN, GERMANY SP European Soc Cardiol C1 Massachusetts Gen Hosp Harvard, CIID, Charlestown, MA USA. Massachusetts Gen Hosp Harvard, CVRC, Charlestown, MA USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. New England Med Ctr Tufts, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2002 VL 23 SU S BP 174 EP 174 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 624HB UT WOS:000179753300655 ER PT J AU Ammer, R Aretz, T Keane, D Ruskin, JN AF Ammer, R Aretz, T Keane, D Ruskin, JN TI Induction of apoptosis in atrial and Bcl-2 upregulation in ventricular myocytes is a transient phenomenon in persistent atrial fibrillation SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 31-SEP 04, 2002 CL BERLIN, GERMANY SP European Soc Cardiol C1 Univ Klinkum Munster, Dept Cardiol, Munster, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2002 VL 23 SU S BP 281 EP 281 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 624HB UT WOS:000179753301053 ER PT J AU Dotani, MI Morise, A Prabhakar, G Haque, R Jain, A Hobbs, G Gibson, CM AF Dotani, MI Morise, A Prabhakar, G Haque, R Jain, A Hobbs, G Gibson, CM TI Pre-operative simvastatin therapy improves resting myocardial blood flow after CABG SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 31-SEP 04, 2002 CL BERLIN, GERMANY SP European Soc Cardiol C1 WVUH, Morgantown, WV USA. BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2002 VL 23 SU S BP 417 EP 417 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 624HB UT WOS:000179753301565 ER PT J AU Messas, E Hagege, A Desnos, M Levine, RA Amar, S AF Messas, E Hagege, A Desnos, M Levine, RA Amar, S TI Elevated proinflammatory mediators correlate with the progression of P. gingivalis infection atherosclerosis in an ApoE (+/-) murine model SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 31-SEP 04, 2002 CL BERLIN, GERMANY SP European Soc Cardiol C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Boston Univ, Boston, MA 02215 USA. Hop Europeen Georges Pompidou, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2002 VL 23 SU S BP 422 EP 422 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 624HB UT WOS:000179753301584 ER PT J AU Wong, M Barlera, S Staszewsky, L Baselier, MRP Naidoo, DP Souttern, S Aknay, N Anand, I AF Wong, M Barlera, S Staszewsky, L Baselier, MRP Naidoo, DP Souttern, S Aknay, N Anand, I TI Pre-trial severity of left ventricular dysfunction in heart failure determines outcomes: Val-HeFT echocardiography study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 31-SEP 04, 2002 CL BERLIN, GERMANY SP European Soc Cardiol C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy. Ampia Ziekenhuis, Breda, Netherlands. King Edward VII Hosp, Durban, South Africa. Wythenshawe Hosp, Manchester M23 9LT, Lancs, England. Novartis Pharmaceut Corp, E Hanover, NJ USA. Univ Minnesota, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2002 VL 23 SU S BP 450 EP 450 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 624HB UT WOS:000179753301692 ER PT J AU Haq, S Kilter, H Andreucci, M Michael, A Force, T AF Haq, S Kilter, H Andreucci, M Michael, A Force, T TI The role of PKCz and cPLA2 in the negative regulation of IGF-1 signaling and cardiac growth SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 31-SEP 04, 2002 CL BERLIN, GERMANY SP European Soc Cardiol C1 MCRI, New England Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Renal Dept, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2002 VL 23 SU S BP 632 EP 632 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 624HB UT WOS:000179753302342 ER PT J AU Hu, JCC Sun, XL Zhang, CH Liu, SX Bartlett, JD Simmer, JP AF Hu, JCC Sun, XL Zhang, CH Liu, SX Bartlett, JD Simmer, JP TI Enamelysin and kallikrein-4 mRNA expression in developing mouse molars SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE KLK4; EMSP1; enamel; MMP-20; enamelysin ID MATRIX METALLOPROTEINASE-20; DENTIN PHOSPHOPROTEIN; MOLECULAR-CLONING; FREE AREAS; AMELOGENIN; RAT; IDENTIFICATION; PURIFICATION; MMP-20; TOOTH AB Proteolytic processing and degradation of enamel matrix proteins appears to be an essential feature of dental enamel formation. The source and character of proteolytic activity in the enamel matrix of developing teeth changes as enamel formation progresses. Two proteinases have been isolated from the extracellular enamel matrix of developing teeth: enamelysin (MMP-20), a matrix metalloproteinase, and kallikrein-4 (KLK4), a serine proteinase. Here, we ask if the expression of MMP-20 and KLK4 correlate with the stage-associated changes in the digestion of enamel proteins. Using in situ hybridization, we localized MMP-20 and KLK4 mRNA in mouse maxillary first molars on postnatal days 1, 2, 3, 5, 6, 7, 9, 11, and 14. Enamelysin signal was first detected in preameloblasts, ameloblasts, and odontoblasts on day 2, but not in ameloblasts covering the enamel-free zone. Enamelysin signal declined in ameloblasts on day 6 but persisted in the dental pulp. In contrast, KLK4 transcripts were first observed on day 3 in pulp and on day 6 in ameloblasts covering the enamel-free zone. the KLK4 signal was present in maturation-stage ameloblasts on days 9, 11, and 14. The expression patterns of MMP-20 and KLK4 by ameloblasts in mouse molars are stage-specific and complementary. C1 Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, San Antonio, TX 78229 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. RP Simmer, JP (reprint author), Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIDCR NIH HHS [DE13221, DE13237, R01 DE014084, R01-DE12769] NR 35 TC 87 Z9 88 U1 2 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD AUG PY 2002 VL 110 IS 4 BP 307 EP 315 DI 10.1034/j.1600-0722.2002.21301.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 578YZ UT WOS:000177149800006 PM 12206593 ER PT J AU Huisman, TAGM Martin, E Kubik-Huch, R Marincek, B AF Huisman, TAGM Martin, E Kubik-Huch, R Marincek, B TI Fetal magnetic resonance imaging of the brain: technical considerations and normal brain development SO EUROPEAN RADIOLOGY LA English DT Review DE fetal MRI; brain development; myelination; migration; sulcation ID HASTE SEQUENCE; IN-UTERO; MR; FETUS; ANATOMY; RECOMMENDATIONS; MATURATION; MIGRATION; EXPOSURE AB Fetal MRI examines non-invasively the unborn fetus. Ultrafast MRI sequences effectively suppress fetal motion. Multiple case reports and studies have shown that fetal MRI is particularly helpful in the evaluation of the central nervous system. The high contrast-to-noise ratio, the high spatial resolution, the multiplanar capabilities, the large field of view and the simultaneous visualisation of fetal and maternal structures have proven to be advantageous. Fetal MRI is particularly helpful in the evaluation of the normal and pathological development of the brain. Despite the fact that no side effects have been reported or are to be expected, the use of MRI during pregnancy is still limited to the second and third trimester of pregnancy. Magnetic resonance imaging contrast media are not to be used as it passes the placenta. Ultrasound remains the primary screening modality for fetal pathology; fetal MRI can serve as an adjunct or second-line imaging modality. C1 Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. Univ Childrens Hosp, Dept Neuroradiol & Magnet Resonance, CH-08091 Zurich, Switzerland. RP Huisman, TAGM (reprint author), Massachusetts Gen Hosp, Mail Code CNT 149-2301,Bldg 149,13th St, Boston, MA 02114 USA. OI Kubik-Huch, Rahel A./0000-0002-3636-8697 NR 50 TC 54 Z9 65 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD AUG PY 2002 VL 12 IS 8 BP 1941 EP 1951 DI 10.1007/s00330-001-12090-x PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 584EX UT WOS:000177455200007 PM 12136312 ER PT J AU Huisman, TAGM Wisser, J Martin, E Kubik-Huch, R Marincek, B AF Huisman, TAGM Wisser, J Martin, E Kubik-Huch, R Marincek, B TI Fetal magnetic resonance imaging of the central nervous system SO EUROPEAN RADIOLOGY LA English DT Review DE fetal MRI; brain malformation; brain pathology ID VENTRICULAR DILATATION INUTERO; PRENATAL-DIAGNOSIS; CLINICAL-SIGNIFICANCE; POSTERIOR-FOSSA; MR; FETUSES; ULTRASOUND; SONOGRAPHY; ANOMALIES; ABNORMALITIES AB Prenatal ultrasonography is the primary screening modality for the evaluation of fetal pathology. Ultrafast fetal MRI is a recent development that examines the fetus in uteto. The short acquisition times (as short as 400 ms/slice) allow to picture freeze the fetus without the need for fetal sedation. The high spatial resolution, good contrast-to-noise ratio, and the multiplanar capabilities are especially advantageous in pathologies of the fetal central nervous system (CNS). Fetal MRI currently serves as a second-line imaging tool for complex fetal cerebral malformations and pathologies. Fetal ventriculomegaly, lesions within the posterior fossa, and abnormalities in cerebral myelination, migration, and sulcation are particularly well identified. C1 Univ Hosp, Inst Diagnost Radiol, Zurich, Switzerland. Univ Hosp, Clin Obstet, Zurich, Switzerland. Univ Childrens Hosp, Dept Neuroradiol & Magnet Resonance, Zurich, Switzerland. RP Huisman, TAGM (reprint author), Massachusetts Gen Hosp, Mail Code CNY 149-2301,Bldg 149,13th St, Boston, MA 02114 USA. OI Kubik-Huch, Rahel A./0000-0002-3636-8697 NR 41 TC 36 Z9 38 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD AUG PY 2002 VL 12 IS 8 BP 1952 EP 1961 DI 10.1007/s00330-001-1281-2 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 584EX UT WOS:000177455200008 PM 12136313 ER PT J AU Morrell, MJ Arabi, Y Zahn, BR Meyer, KC Skatrud, JB Badr, MS AF Morrell, MJ Arabi, Y Zahn, BR Meyer, KC Skatrud, JB Badr, MS TI Effect of surfactant on pharyngeal mechanics in sleeping humans: implications for sleep apnoea SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE apnoea; breathing; human; sleep; surfactant ID UPPER AIRWAY PATENCY; PRESSURE; TENSION AB Instillation of surfactant into the pharyngeal lumen reduces the pressure required to reopen an occluded airway, and decreases the apnoea/hypopnoea index (AHI). The authors hypothesised that surfactant also reduces the sleep-related increase in pharyngeal resistance. To test this hypothesis two single blind, crossover, placebo-controlled studies were performed. In protocol A seven male, asymptomatic snoring subjects were studied during sleep. Inspiratory pharyngeal resistance vas calculated from plots of airflow versus supraglottic pressure (seven breaths) before and after surfactant or saline instillation. In protocol B, in a different group of seven male subjects with sleep apnoea (AHI 15.2 (12) events.h(-1)) the effect of surfactant or saline on sleep disordered breathing vas measured, for 1 h immediately before and after surfactant or saline instillation. Surfactant decreased pharyngeal resistance calculated at peak, pressure (group mean (SD): pre versus post 83.7 (76.4) versus 49.4 (71.1) cmH(2)O.L-1.s(-1)) and significantly reduced the respiratory disturbance index (RDI pre versus post 79.7 (58.7) versus 59.6 (56.9) events.h(-1)). Saline did not decrease resistance (pre versus post 58.6 (31.1) versus 72.5 (73.4) cmH2O.L-1.s(-1)) or RDI (pre versus post 75.3 (42.4) versus 79.9 (46.1) events.h(-1)). Surfactant reduced the collapsibility of the pharynx and led to a modest reduction in respiratory disturbance index. The authors speculate that surfactant may delay occlusion by reducing the liquid "bridging" within the folded pharyngeal lining. C1 Univ London Imperial Coll Sci Technol & Med, Sleep & Ventilat Unit, Sch Med,Natl Heart & Lung Inst, Royal Brompton Hosp, London SW3 6NP, England. Univ Wisconsin, Madison, WI USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. Wayne State Univ, Detroit VA Med Ctr, Detroit, MI USA. RP Morrell, MJ (reprint author), Univ London Imperial Coll Sci Technol & Med, Sleep & Ventilat Unit, Sch Med,Natl Heart & Lung Inst, Royal Brompton Hosp, London SW3 6NP, England. NR 17 TC 25 Z9 26 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD AUG PY 2002 VL 20 IS 2 BP 451 EP 457 DI 10.1183/09031936.02.00273702 PG 7 WC Respiratory System SC Respiratory System GA 587LE UT WOS:000177641400033 PM 12212981 ER PT J AU Brady, KT Sonne, SC Malcolm, RJ Randall, CL Dansky, BS Simpson, K Roberts, JS Brondino, M AF Brady, KT Sonne, SC Malcolm, RJ Randall, CL Dansky, BS Simpson, K Roberts, JS Brondino, M TI Carbamazepine in the treatment of cocaine dependence: Subtyping by affective disorder SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; PSYCHIATRIC-DIAGNOSIS; DEPRESSIVE-DISORDERS; FLUOXETINE TREATMENT; ANTIMANIC EFFICACY; BIPOLAR DISORDERS; ACUTE MANIA; LITHIUM; ABUSE AB Studies investigating carbamazepine (CBZ) in the treatment of cocaine dependence have been inconsistent. In this study, cocaine-dependent individuals with (n = 57) and without (n = 82) affective disorder were compared in a 12-week, double-blind, placebo-controlled trial. Urine drug screens (UDS) and self-report of drug use were collected weekly. Affective symptoms were measured monthly, Subjects receiving CBZ attended more medication sessions (p = .03). The CBZ-treated affective group had a trend toward fewer cocaine-positive UDS (p = .08) and a significantly longer time to first cocaine use (p = .06). CBZ treatment did not have any impact on cocaine use in individuals without affective disorders. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Pharm Practice, Charleston, SC 29401 USA. CB Technol, Exton, PA USA. Univ Maryland, Depmeasurement Stat & Evaluat, College Pk, MD 20742 USA. Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. RP Brady, KT (reprint author), Med Univ S Carolina, Clin Trial Network, Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St,Room B523, Charleston, SC 29401 USA. FU NIDA NIH HHS [DA07761] NR 57 TC 40 Z9 40 U1 4 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD AUG PY 2002 VL 10 IS 3 BP 276 EP 285 DI 10.1037//1064-1297.10.3.276 PG 10 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 588QJ UT WOS:000177711900012 PM 12233988 ER PT J AU Kinner, B Zaleskas, JM Spector, M AF Kinner, B Zaleskas, JM Spector, M TI Regulation of smooth muscle actin expression and contraction in adult human mesenchymal stem cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE smooth muscle actin; contraction; stem cells; TGF-beta 1; PDGF-BB ID COLLAGEN-GAG MATRICES; HUMAN ARTICULAR CHONDROCYTES; TERM MARROW CULTURES; GROWTH FACTOR-BETA; STROMAL CELLS; IN-VITRO; DIFFERENTIATION PATHWAY; HUMAN-FIBROBLASTS; CROSS-LINKING; INVITRO AB Prior studies have demonstrated the expression of a contractile actin isoform, a-smooth muscle actin, in bone marrow stromal cells. One objective of the current study was to correlate contractility with a-smooth muscle actin expression in human bone marrow stroma-derived mesenchymal stem cells. A second objective was to determine the effects of transforming growth factor-beta1, platelet derived growth factor-BB, and a microfilament-modifying agent on a-smooth muscle actin expression and a-smooth muscle actin-enabled contraction. Adult human bone marrow stromal cells were passaged in monolayer and their inducibility to chondrocytic, osteoblastic, and adipogenic phenotypes was demonstrated. Western blot analysis was employed along with densitometry to quantify the a-smooth muscle actin content of the cells and their contractility was evaluated by their contraction of a type I collagen-glycosaminoglycan sponge-like matrix into which they were seeded. Transforming growth factor-pi (I ng/ml) significantly increased and platelet-derived growth factor-BB (10 ng/ml) decreased a-smooth muscle actin expression and the contractility of the cells. Cytochalasin D also blocked cell contraction. There was a notably high correlation of cell-mediated contraction normalized to the DNA content of the matrices with a-smooth muscle actin content of the cells by linear regression analysis (R-2 = 0.88). These findings lay the groundwork for considering the role of a-smooth muscle actin-enabled contraction in mesenchymal stem cells and in their connective tissue cell progeny. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. RP Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, 75 Francis St,MRB 106, Boston, MA 02115 USA. NR 57 TC 161 Z9 172 U1 2 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 1 PY 2002 VL 278 IS 1 BP 72 EP 83 DI 10.1006/excr.2002.5561 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 577PT UT WOS:000177071000008 PM 12126959 ER PT J AU Jensen, DM Kovacs, TOG Jutabha, R Machicado, GA Gralnek, IM Savides, TJ Smith, J Jensen, ME Alofaituli, G Gornbein, J AF Jensen, DM Kovacs, TOG Jutabha, R Machicado, GA Gralnek, IM Savides, TJ Smith, J Jensen, ME Alofaituli, G Gornbein, J TI Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots SO GASTROENTEROLOGY LA English DT Article ID BLEEDING PEPTIC-ULCERS; ND-YAG LASER; HEATER PROBE AB Background & Aims: Treatment of high-risk patients with nonbleeding adherent clots on ulcers is controversial. In a previous randomized trial, there was no benefit to endoscopic therapies compared with medical therapy for prevention of ulcer rebleeding. Our purpose was to test the hypothesis that patients treated with combination endoscopic therapy would have significantly lower rebleeding rates than those treated with medical therapy. Methods: In this randomized, controlled trial, 32 high-risk patients with severe ulcer hemorrhage and nonbleeding adherent clots resistant to target irrigation were randomized to medical therapy or to combination endoscopic therapy (with epinephrine injection, shaving down the clot with cold guillotining, and bipolar coagulation on the underlying stigmata). Physicians blinded to the endoscopic therapy managed all patients. Results: Patients were similar at study entry, except for older age in the medical group and lower platelet count in the endoscopic group. By hospital discharge, significantly more medically treated patients (6/17; 35.3%) than endoscopically treated patients (0/15; 0%) rebled (P = 0.011). There were no complications of endoscopic treatment. Conclusions: Combination endoscopic therapy of nonbleeding adherent clots significantly reduced early ulcer rebleeding rates in high-risk patients compared with medical therapy alone. This endoscopic treatment was safe. C1 Univ Calif Los Angeles, Sch Med, Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst,CURE, Los Angeles, CA 90073 USA. Northridge Hosp Med Ctr, Van Nuys, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Oschner Fdn Clin, New Orleans, LA USA. RP Jensen, DM (reprint author), Univ Calif Los Angeles, Sch Med, Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst,CURE, Bldg 115,Room 318, Los Angeles, CA 90073 USA. RI smith, james/C-9922-2016 FU NIDDK NIH HHS [1K24DK 02650, DK 41301, R01 DK 33273] NR 20 TC 99 Z9 103 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2002 VL 123 IS 2 BP 407 EP 413 DI 10.1053/gast.2002.34782 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 577WK UT WOS:000177085400004 PM 12145792 ER PT J AU Yamaoka, Y Kikuchi, S El-Zimaity, HMT Gutierrez, O Osato, MS Graham, DY AF Yamaoka, Y Kikuchi, S El-Zimaity, HMT Gutierrez, O Osato, MS Graham, DY TI Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production SO GASTROENTEROLOGY LA English DT Article ID ANTIGEN-BINDING ADHESIN; EPITHELIAL-CELLS; INCREASED RISK; PATHOGENICITY ISLAND; CAGA STATUS; INFECTION; VACA; GENE; ICEA; GENOTYPES AB Background & Aims: Disease-associated virulence factors of Helicobacter pylori may not be independent of one another. The aim was to determine which H. pylori virulence factor(s) was the most important predictor of severity of gastric inflammation or clinical outcome. Metho : cag Pathogenicity island (PAI), vacA, babA2, and iceA status were determined by polymerase chain reaction (PCR). oipA functionality was based on switch status determined by PCR-based sequencing. A backward stepwise multiple regression analysis was performed to determine which factor(s) was the most discriminating for clinical outcome as well as the relationship to mucosal histology (H. pylori density, neutrophil infiltration, intestinal metaplasia, and gastric atrophy) and mucosal interleukin 8 (IL-8) production. Results: H. pylori were obtained from 247 patients (86 with gastritis, 86 with duodenal ulcer, and 75 with gastric carcinoma). Although oipA status was closely linked to specific cag PAI, vacA, and babA2 genotypes, only oipA status remained in the final model to discriminate duodenal ulcer from gastritis (adjusted odds ratio [OR] = 5 and 95% confidence interval [CI] = 2.1-11.9). Among the factors, only a functional oipA was significantly associated with high H. pylori density, severe neutrophil infiltration, and high mucosal IL-8 levels (P < 0.001). oipA status had no relationship to gastric atrophic changes. Conclusions: oipA functional status was related to clinical presentation, H. pylori density, and gastric inflammation. cag PAI, babA2, or vacA status appear important only as surrogate markers for a functional oipA gene. C1 Vet Affairs Med Ctr 111D, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Aichi Med Univ, Sch Med, Dept Publ Hlth, Aichi, Japan. Univ Nacl Colombia, Dept Med, Bogota, Colombia. RP Yamaoka, Y (reprint author), Vet Affairs Med Ctr 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [DK56338, DK53659] NR 40 TC 181 Z9 195 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2002 VL 123 IS 2 BP 414 EP 424 DI 10.1053/gast.2002.34781 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 577WK UT WOS:000177085400005 PM 12145793 ER PT J AU El-Serag, HB Kunik, M Richardson, P Rabeneck, L AF El-Serag, HB Kunik, M Richardson, P Rabeneck, L TI Psychiatric disorders among veterans with hepatitis C infection SO GASTROENTEROLOGY LA English DT Article ID INJECTION-DRUG USERS; VIRUS-INFECTION; MENTAL-DISORDERS; HIV-INFECTION; RISK; PREVALENCE; AFFAIRS; INTERFERON; DEPRESSION; RECORDS AB Background & Aims: The presence of psychiatric, drug-, and alcohol-use disorders in hepatitis C virus (HCV)-infected patients may influence their management and prognosis. The frequency and the risk for these disorders among HCV-infected patients are unknown. Methods: We identified all HCV-infected veteran patients who were hospitalized during 1992-1999 and searched the inpatient and outpatient computerized files for pre-defined psychiatric, drug-, and/or alcohol-use disorders. We then performed a case-control study among Vietnam veterans; controls without HCV were randomly chosen from hospitalized patients. Results: We identified 33,824 HCV-infected patients, in whom 86.4% had at least one past or present psychiatric, drug-, or alcohol-use disorder recorded. However, only 31% had active disorders as defined by hospitalization to psychiatric,or drug-detoxification bed sections. There were 22,341 HCV-infected patients from the Vietnam period of service (cases) who were compared with 43,267 patients without HCV (controls). Cases were more likely to have depressive disorders (49.5% vs. 39.1%), posttraumatic stress disorder (PTSD) (33.5% vs. 24.5%), psychosis (23.7% vs. 20.9%), bipolar disorder (16.0% vs. 12.6%), anxiety disorders (40.8% vs. 32.9%), alcohol (77.6% vs. 45.0%), and drug-use disorders (69.4% vs. 31.1%). In multivariable regression analyses that adjust for age, sex, and ethnicity, drug use, alcohol-use, depression, PTSD, and anxiety remained strongly associated with HCV. Conclusions: Several psychiatric, drug-, and alcohol-use disorders are commonly found among HCV-infected veterans compared with those who are not infected. At least one third of these patients have active disorders. A multidisciplinary approach to the management of HCV-infected patients is needed. C1 Houston Vet Affairs Med Ctr 152, Houston, TX 77030 USA. Houston Ctr Qual Care & Utilizat Studies, Gastroenterol Sect, Houston, TX 77030 USA. Houston Ctr Qual Care & Utilizat Studies, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [1 K24 DKK 59318-01] NR 33 TC 133 Z9 136 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2002 VL 123 IS 2 BP 476 EP 482 DI 10.1053/gast.2002.34750 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 577WK UT WOS:000177085400012 PM 12145801 ER PT J AU Mallery, JS Centeno, BA Hahn, PF Chang, YC Warshaw, AL Brugge, WR AF Mallery, JS Centeno, BA Hahn, PF Chang, YC Warshaw, AL Brugge, WR TI Pancreatic tissue sampling guided by EUS, CT/US, and surgery: a comparison of sensitivity and specificity SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID FINE-NEEDLE ASPIRATION; ENDOSCOPIC ULTRASOUND; PERCUTANEOUS BIOPSY; DIAGNOSTIC-ACCURACY; BRUSH CYTOLOGY; CANCER; CARCINOMA; MASSES; ENDOSONOGRAPHY; EXPERIENCE AB Background. Needle aspiration of the pancreas is performed to differentiate pancreatic malignancy, focal chronic pancreatitis, and metastasis to the pancreas. Biopsies may be directed by using EUS, CT, US, or surgery. This study retrospectively compared the accuracy of EUS-guided, CT/US-guided, and surgical tissue sampling of the pancreas over a 5-year period. Methods: The records of patients undergoing pancreatic tissue sampling were reviewed for a final clinical diagnosis based on the results of cytology, histology, and clinical history. The sensitivity, specificity, and accuracy of each technique were calculated. Results: One hundred forty-nine tissue samples (68 EUS-guided, 70 CT/US-guided, 11 surgical) from 128 patients were compared. There was no significant difference in accuracy rates for EUS (76.4%), CT/US (81.4%), and surgically guided (81.8%) specimens. EUS was used when masses were smaller (2.6 +/- 0.1 cm) as compared with CT/US (3.4 +/- 0.2 cm, p < 0.001) and surgery (2.9 +/- 0.4 cm, p = 0.49). In univariate analyses, factors associated with greater accuracy regardless of technique were as follows: (1) older age, (2) larger size of the mass, and (3) participation by a cytologist during the procedure. A subsequent multivariate logistic regression analysis, in which the examination of the effect of each factor controls for the effect of each of the other factors, found that only older age was a significant predictor of accuracy. Conclusion: EUS-guided tissue sampling of pancreatic masses is as accurate as CT/US-guided sampling and surgical biopsies. C1 Massachusetts Gen Hosp, GI Unit, Dept Med, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit, Dept Med, Blake 452C, Boston, MA 02114 USA. NR 40 TC 99 Z9 105 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 AUG PY 2002 VL 56 IS 2 BP 218 EP 224 AR UNSP 37/1/125826 DI 10.1067/mge.2002.125826 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 580YN UT WOS:000177264500010 PM 12145600 ER PT J AU Farley, KA Shuster, DL Burnett, DS Sisterson, J AF Farley, KA Shuster, DL Burnett, DS Sisterson, J TI Using proton-induced He-3 to study He diffusion kinetics and rock thermal histories SO GEOCHIMICA ET COSMOCHIMICA ACTA LA English DT Meeting Abstract C1 CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RI Shuster, David/A-4838-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0016-7037 J9 GEOCHIM COSMOCHIM AC JI Geochim. Cosmochim. Acta PD AUG PY 2002 VL 66 IS 15A SU 1 BP A224 EP A224 PG 1 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA 583RX UT WOS:000177423400435 ER PT J AU Tornatore, JB Grant, LA AF Tornatore, JB Grant, LA TI Burden among family caregivers of persons with Alzheimer's disease in nursing homes SO GERONTOLOGIST LA English DT Article DE dementia; family caregiver; stress; nursing home; special care unit ID SPECIAL CARE-UNITS; MULTILEVEL ANALYSIS; INFORMAL CAREGIVERS; DEMENTIA SUFFERERS; GENDER DIFFERENCES; PREDICTORS; OUTCOMES; PLACEMENT; HEALTH; POPULATION AB Purpose: This article examines family caregiver burden after placement of a relative with Alzheimer's disease or a related dementia in a nursing home. Design and Methods: A systems-oriented contextual approach was used to study burden in 276 family caregivers. Results: SAS PROC MIXED analysis showed burden to be associated with caregiver age, length of time involved in caregiving, custodial units, involvement in hands-on care, and expectations for care. Implications: The findings suggest that more services aimed at relieving caregiver burden after nursing home placement may be warranted, particularly so for caregivers who are older and for those who had a shorter length of involvement in direct caregiving before institutionalization. C1 VA Puget Sound Hlth Care Syst, Dept Hlth Serv, Seattle, WA USA. Carlson Sch Management, Dept Healthcare Management, Minneapolis, MN USA. RP Tornatore, JB (reprint author), Screen Inc, 8071-2 8th Ave S, Seattle, WA 98108 USA. EM j.tornatore@attbi.com FU NIA NIH HHS [RFA AG-91-06] NR 58 TC 52 Z9 53 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 2002 VL 42 IS 4 BP 497 EP 506 PG 10 WC Gerontology SC Geriatrics & Gerontology GA 580DE UT WOS:000177218800007 PM 12145377 ER PT J AU Locher, JL Burgio, KL Goode, PS Roth, DL Rodriguez, E AF Locher, JL Burgio, KL Goode, PS Roth, DL Rodriguez, E TI Effects of age and causal attribution to aging on health-related behaviors associated with urinary incontinence in older women SO GERONTOLOGIST LA English DT Article DE treatment-seeking; self-management; self-treatment ID TREATMENT-SEEKING; COMMUNITY; SYMPTOMS; CARE; PREVALENCE; PEOPLE; SERVICES; ADULTS; COHORT AB Purpose: The purpose of this study was to assess the effects of age and patients' attribution of incontinence to aging on health-related behaviors associated with incontinence. Design and Methods: Participants in this study were 74 women who either sought treatment for urinary incontinence at a multidisciplinary continence program or volunteered for a randomized clinical trial of behavioral and drug therapy for incontinence. As part of their clinical evaluation, women were interviewed about how they managed their incontinence and their perceptions of what had caused the condition. Self-management of incontinence was defined as behaviors used to cope with incontinence, rather than treat or cure incontinence. Self-treatment was defined as self-implementation of Kegel exercises, and formal treatment was defined as interaction with a health care provider. Results: Over half of the respondents attributed their incontinence to aging. In multivariate analyses, age was associated with self-management of incontinence, but not self-treatment or formal treatment. In contrast, attribution of incontinence to aging was associated with self-management and self-treatment of incontinence. There was also a trend for attribution of incontinence to aging to be associated with formal treatment for incontinence. Women who attributed their incontinence to aging were less likely to have engaged in self-management strategies and to have received a previous evaluation or treatment; but, they were more likely to have engaged in self-treatment for incontinence. When other relevant variables were added to the regression models, perception that incontinence restricted one's activities became the most significant predictor of performing self-management strategies and performing Kegel exercises. Implications: Attribution to aging may be an impediment to seeking treatment. Education to promote understanding of the actual causes and treatment of urinary incontinence may encourage people to seek appropriate intervention. Additionally, whereas attribution to aging is an important factor contributing to health-related behaviors, other factors, such as perception that one's activities are restricted, may play an important role. C1 Univ Alabama, Ctr Aging, Div Gerontol & Geriatr Med, Birmingham, AL USA. Univ Alabama, Dept Sociol, Birmingham, AL 35294 USA. Univ Alabama, Div Gerontol & Geriatr Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. RP Locher, JL (reprint author), CH19,Room 201 N,1530 3rd Ave S, Birmingham, AL 35294 USA. FU NIA NIH HHS [R01AG08010, K01AG00994, R01 AG008010-11, K01 AG000994] NR 44 TC 20 Z9 21 U1 2 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 2002 VL 42 IS 4 BP 515 EP 521 PG 7 WC Gerontology SC Geriatrics & Gerontology GA 580DE UT WOS:000177218800009 PM 12145379 ER PT J AU Zacks, DN Samson, CM Loewenstein, J Foster, CS AF Zacks, DN Samson, CM Loewenstein, J Foster, CS TI Electroretinograms as an indicator of disease activity in birdshot retinochoroidopathy SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID CHORIORETINOPATHY AB Purpose: To determine whether electroretinogram results can help predict the success in tapering of immunosuppressive medication in patients with birdshot retinochoroidopathy. Methods: Fifteen patients with birdshot retinochoroidopathy who had at least three serial electroretinograms (ERG) during the course of their disease were included in the study. Charts of patients seen at the Immunology and Uveitis Service at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts were retrospectively reviewed. Seven parameters of the ERGs were examined: dim scotopic amplitude, bright scotopic amplitude, bright scotopic implicit time, single-flash photopic amplitude, single-flash photopic implicit time, 30 Hz flicker amplitudes, and 30 Hz flicker implicit times. For each parameter the patients were divided into two groups, those with normal and those with abnormal responses at the time their immunosuppressive medication taper was initiated. The percentage of patients in each group who were able to successfully taper their immunosuppressive medication was calculated. A successful taper of medication was defined as no recurrence of disease signs or symptoms for at least 1 year after the medication was terminated. Results: Abnormalities in the bright scotopic response amplitudes and 30 Hz flicker implicit times were associated with recurrence of inflammation as immunosuppressive. therapy was tapered. Conclusion: ERG can serve as a useful adjunct in helping determine when to initiate tapering of immunosuppressive therapy in patients with birdshot retinochoroidopathy. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Serv Immunol, Boston, MA 02114 USA. New York Eye & Ear Infirm, Uveitis Serv, New York, NY 10003 USA. RP Zacks, DN (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, 243 Charles St, Boston, MA 02114 USA. RI Zacks, David/I-4394-2013; OI Zacks, David/0000-0001-8592-5165 NR 10 TC 30 Z9 34 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD AUG PY 2002 VL 240 IS 8 BP 601 EP 607 DI 10.1007/s00417-002-0506-7 PG 7 WC Ophthalmology SC Ophthalmology GA 594UG UT WOS:000178068900001 PM 12192452 ER PT J AU Nogueira, IP Biggs, PJ AF Nogueira, IP Biggs, PJ TI Measurement of TVLs in lead for 4, 6 and 10 MV Bremsstrahlung X-ray beams at scattering angles between 30 and 135 SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT 38th AAPM Annual Meeting CY JUL 21-25, 1996 CL PHILADELPHIA, PA SP AAPM DE photons; shielding; Monte Carlo; lead AB Measurements have been made of the transmission factors through lead for scattered radiation produced by 4, 6, and 10 MV bremsstrahlung x-ray beams incident on a polystyrene phantom; these measurements cover the range of scattering angles between 30degrees and 135degrees. The results show that the tenth value layer (TVL) for scattered radiation decreases sharply with increasing scattering angle and increases slightly with increasing beam energy, although at large scattering angles there is little energy dependence. TVLs range from 3.5 cm to 0.3 cm for 4 MV at scattering angles between 30degrees and 135degrees, from 3.8 cm to 0.6 cm for 6 MV, and from 4.2 cm to 0.7 cm for 10 MV, respectively, at scattering angles between 30degrees and 120degrees. Monte Carlo calculations, performed at 4 MV to simulate the transmission of scattered radiation, are in good agreement with the experimental measurements. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Biggs, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM pjbiggs@partners.org NR 16 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2002 VL 83 IS 2 BP 255 EP 260 DI 10.1097/00004032-200208000-00010 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 574JR UT WOS:000176886200010 PM 12132713 ER PT J AU Rubenstein, LV Parker, LE Meredith, LS Altschuler, A dePillis, E Hernandez, J Gordon, NP AF Rubenstein, LV Parker, LE Meredith, LS Altschuler, A dePillis, E Hernandez, J Gordon, NP TI Understanding team-based quality improvement for depression in primary care SO HEALTH SERVICES RESEARCH LA English DT Article DE quality improvement; depression; primary care; health care provider teams ID MANAGED PRIMARY-CARE; HEALTH-CARE; COLLABORATIVE MANAGEMENT; MAJOR DEPRESSION; IMPACT; OUTCOMES; ILLNESS; TRIAL AB Objective. To assess the impacts of the characteristics of quality improvement (QI) teams and their environments on team success in designing and implementing high quality, enduring depression care improvement programs in primary care (PC) practices. Study Setting/Data Sources. Two nonprofit managed care organizations sponsored five QI teams tasked with improving care for depression in large PC practices. Data on characteristics of the teams and their environments is from observer process notes, national expert ratings, administrative data, and interviews. Study Design. Comparative formative evaluation of the quality and duration of implementation of the depression improvement programs developed by Central Teams (CTs) emphasizing expert design and Local Teams (LTs) emphasizing participatory local clinician design, and of the effects of additional team and environmental factors on each type of team. Both types of teams depended upon local clinicians for implementation. Principal Findings. The CT intervention program designs were more evidence-based than those of LTs. Expert team leadership, support from local practice management, and support from local mental health specialists strongly influenced the development of successful team programs. The CTs and LTs were equally successful when these conditions could be met, but CTs were more successful than LTs in less supportive environments. Conclusions. The LT approach to QI for depression requires high local support and expertise from primary care and mental health clinicians. The CT approach is more likely to succeed than the LT approach when local practice conditions are not optimal. C1 RAND Corp, Hlth Program, Santa Monica, CA 90401 USA. Va Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Hawaii, Hilo, HI 96720 USA. Quintiles Transat Inc, E Business Prod & Serv, San Francisco, CA USA. RP Rubenstein, LV (reprint author), RAND Corp, Hlth Program, 1700 Main St, Santa Monica, CA 90401 USA. FU NIMH NIH HHS [U01-MH50732] NR 28 TC 58 Z9 58 U1 1 U2 6 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2002 VL 37 IS 4 BP 1009 EP 1029 DI 10.1034/j.1600-0560.2002.63.x PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 591PQ UT WOS:000177889800012 PM 12236381 ER PT J AU Cramer, SC Weisskoff, RM Schaechter, JD Nelles, G Foley, M Finklestein, SP Rosen, BR AF Cramer, SC Weisskoff, RM Schaechter, JD Nelles, G Foley, M Finklestein, SP Rosen, BR TI Motor cortex activation is related to force of squeezing SO HUMAN BRAIN MAPPING LA English DT Article DE functional MRI; grip force; human; dynamometer; motor cortex ID PRECISION-GRIP; FUNCTIONAL MRI; SOMATOSENSORY CORTEX; NEURONAL-ACTIVITY; MOVEMENT RATE; STROKE; MONKEY; BRAIN; SENSORIMOTOR; PERFORMANCE AB Primate studies have demonstrated that motor cortex neurons show increased activity with increased force of movement. In humans, this relationship has received little study during a power grip such as squeezing, and has previously only been evaluated across a narrow range of forces. Functional MRI was performed in eight healthy subjects who alternated between rest and right hand squeezing at one of three force levels. During scanning, motor performances were recorded using a dynamometer. At each force level, activation volume was measured within left sensorimotor cortex, right sensorimotor cortex, and a midline supplementary motor area. In left sensorimotor cortex, % signal change was also assessed. The range of force generated across the three force levels varied from 4.9 N to 276 N. In left sensorimotor cortex, activation volume increased significantly with greater force. The % signal change also increased with greater force and correlated closely with activation volume. In supplementary motor area, activation volume increased significantly with increasing force, but with greater intersubject variability. In right sensorimotor cortex, a trend for larger activation volumes with greater force did not reach significance. The laterality index, an expression of the relative degree of contralateral vs. ipsilateral sensorimotor cortex activation, did not change across the three force levels. Increased force of squeezing is associated with increased contralateral sensorimotor cortex and supplementary motor area activation. This relationship was found across the full spectrum of forces that the human hand is capable of generating. Use of a valid, reliable method for assessing motor behavior during functional MRI may be important to clinical applications. (C) 2002 Wiley-Liss, Inc. C1 Dept Radiol, MGH, NMR Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. RP Cramer, SC (reprint author), Univ Washington, 1959 NE Pacific St,Box 356465,Room RR-650, Seattle, WA 98195 USA. NR 49 TC 92 Z9 92 U1 2 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD AUG PY 2002 VL 16 IS 4 BP 197 EP 205 DI 10.1002/hbm.10040 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 579KJ UT WOS:000177176900001 PM 12112762 ER PT J AU Parhami-Seren, B Haberly, R Margolies, MN Haupert, GT AF Parhami-Seren, B Haberly, R Margolies, MN Haupert, GT TI Ouabain-binding protein(s) from human plasma SO HYPERTENSION LA English DT Article DE ouabain; digitalis-like factor; immunoglobulins; sodium pump ID AZOPHENYLARSONATE-SPECIFIC ANTIBODIES; DIGITALIS-LIKE COMPOUNDS; K+-ATPASE INHIBITOR; ENDOGENOUS OUABAIN; PEPTIDE LIBRARIES; ADRENAL-CELLS; NA+; RAT; PURIFICATION; GLYCOSIDES AB Conservation of the binding site on mammalian Na+,K+-ATPase for cardiac glycosides and the importance of the Na+ pump in mammalian cellular physiology has stimulated the search for a mammalian analog of these plant compounds. One candidate, isolated from brain and blood, appears to be ouabain itself or a closely related isomer, the ouabain-like compound. Little is known about the circulating form. Because human steroid hormones circulate with carrier proteins, we produced a ouabain-specific monoclonal antibody (mAb 1-10) and used it to probe normal human plasma for ouabain-protein carrier complex. Ouabain-like biological activity was isolated in association with protein bands of 80, 50, and 25 kDa. These proteins appear to be human immunoglobulins or immunoglobulin-like because they are recognized by anti-human immunoglobulin antibodies, but not by anti-mouse immunoglobulin antibodies. The protein-containing fractions inhibit the binding of mAb 1-10 to immobilized ouabain, and with further purification on protein A, the immunoglobulin-like protein binds radioactive ouabain with an IC50 of 200 to 600 nmol/L, but binds digoxin with 100-fold less affinity, suggesting specificity for ouabain or its isomer. Active protein fractions after purification on C-18 inhibit Na+ pump activity in human erythrocytes (IC(50approximate to)4 nmol/L, ouabain equivalents), and this chromatography appears to dissociate the ouabain-like compound from the immunoglobulin protein(s). These immunoglobulin-like molecules may represent a subset of immunoglobulins (less than or equal to0.5% of total protein A immunoglobulin) that function as a reservoir and delivery system for ouabain-like compounds in the modulation of human Na+,K+-ATPase in vivo. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Renal Unit, Boston, MA USA. RP Haupert, GT (reprint author), Massachusetts Gen Hosp, Renal Unit, CNY 8, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA24432]; NHLBI NIH HHS [R01 HL52282, HL47415]; NIAID NIH HHS [R29AI33175] NR 32 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD AUG PY 2002 VL 40 IS 2 BP 220 EP 228 DI 10.1161/01.HYP.0000027134.14160.1D PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 582BW UT WOS:000177330700019 PM 12154117 ER PT J AU Arnaout, MA AF Arnaout, MA TI Integrin structure: new twists and turns in dynamic cell adhesion SO IMMUNOLOGICAL REVIEWS LA English DT Review ID GLYCOPROTEIN-IIB-IIIA; FUNCTION-ASSOCIATED ANTIGEN-1; PHOTOAFFINITY CROSS-LINKING; CALCIUM-BINDING DOMAIN; AMINO-ACID-RESIDUES; MONOCLONAL-ANTIBODY EPITOPES; BETA-PROPELLER DOMAIN; CYSTEINE-RICH REGION; CD11B A-DOMAIN; LIGAND-BINDING AB The divalent-cation-dependent binding of alphabeta heterodimeric integrins to their ligands regulates most cellular processes. Integrin-ligand interactions are tightly controlled by inside-out activation signals. Ligand-bound integrins transduce outside-in signals typical of other receptors. Precise information of how ligands bind to integrins is restricted to that of a small vWF A-type domain present in some alpha-subunits (alphaA). Both inside-out and outside-in signals elicit tertiary and quaternary changes in integrins, but the precise nature and scope and of these changes are unknown. The recently solved structures of the extracellular segment of integrin alphaVbeta3 in its unliganded and liganded states are generating exciting new insights into the design, wiring, function and regulation of this protein family. The structures reveal a surprising degree of flexibility at defined regions in the structure that is potentially controlled by cations. The quaternary structure of the ligand-binding region bears a striking resemblance to the nucleotide-binding pocket of G-proteins, implying analogous signaling mechanisms. Structural links exist through which ligand-induced tertiary changes may be translated into quaternary changes and vice versa . The structures also raise the tantalizing hypothesis that alphaA is a regulated endogenous integrin ligand, so that no special regulatory features are needed in this integrin. These findings provide the framework for new investigations of structure-activity relationships in integrins, with important implications for targeting these receptors therapeutically. C1 Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu NR 138 TC 72 Z9 76 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2002 VL 186 BP 125 EP 140 DI 10.1034/j.1600-065X.2002.18612.x PG 16 WC Immunology SC Immunology GA 594HE UT WOS:000178043100012 PM 12234368 ER PT J AU Takagi, J Springer, TA AF Takagi, J Springer, TA TI Integrin activation and structural rearrangement SO IMMUNOLOGICAL REVIEWS LA English DT Review ID FUNCTION-ASSOCIATED ANTIGEN-1; BETA-PROPELLER DOMAIN; GLYCOPROTEIN-IIB-IIIA; I-LIKE DOMAIN; INTERCELLULAR-ADHESION MOLECULE-1; SUBUNIT CYTOPLASMIC DOMAIN; CYSTEINE-RICH REPEATS; P-ARYLTHIO CINNAMIDES; AMINO-ACID-RESIDUES; C-TERMINAL REGION AB Among adhesion receptor families, integrins are particularly important in biological processes that require rapid modulation of adhesion and de-adhesion. Activation on a timescale of < 1 s of beta2 integrins on leukocytes and beta3 integrins on platelets enables deposition of these cells at sites of inflammation or vessel wall injury. Recent crystal, nuclear magnetic resonance (NMR), and electron microscope (EM) structures of integrins and their domains lead to a unifying mechanism of activation for both integrins that contain and those that lack an inserted (I) domain. The I domain adopts two alternative conformations, termed open and closed. In striking similarity to signaling G-proteins, rearrangement of a Mg2+ -binding site is linked to large conformational movements in distant backbone regions. Mutations that stabilize a particular conformation show that the open conformation has high affinity for ligand, whereas the closed conformation has low affinity. Movement of the C-terminal alpha-helix 10 Angstrom down the side of the domain in the open conformation is sufficient to increase affinity at the distal ligand-binding site 9000-fold. This C-terminal "bell-rope" provides a mechanism for linkage to conformational movements in other domains. Recent structures and functional studies reveal interactions between beta-propeller, I, and I-like domains in the integrin headpiece, and a critical role for integrin epidermal growth factor (EGF) domains in the stalk region. The headpiece of the integrin faces down towards the membrane in the inactive conformation, and extends upward in a "switchblade"-like opening upon activation. These long-range structural rearrangements of the entire integrin molecule involving interdomain contacts appear closely linked to conformational changes within the I and I-like domains, which result in increased affinity and competence for ligand binding. C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Ctr Blood Res, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu FU NCI NIH HHS [CA31799, CA31798]; NHLBI NIH HHS [HL48675] NR 111 TC 257 Z9 266 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2002 VL 186 BP 141 EP 163 DI 10.1034/j.1600-065X.2002.18613.x PG 23 WC Immunology SC Immunology GA 594HE UT WOS:000178043100013 PM 12234369 ER PT J AU Weninger, W Manjunath, N von Andrian, UH AF Weninger, W Manjunath, N von Andrian, UH TI Migration and differentiation of CD8(+) T cells SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ACTIVATED KILLER-CELLS; PERIPHERAL LYMPH-NODES; CHEMOKINE RECEPTOR 9; COMMON GAMMA-CHAIN; IN-VIVO; BETA-CHAIN; CD4 GENE; INTERLEUKIN-2 RECEPTOR; MOLECULAR-MECHANISMS; HOMING POTENTIALS AB Antigen-specific responses by CD8(+) T cells require direct cell-cell interactions between T cells and antigen-presenting cells (APC). Initially, naive T cells must communicate with APC in lymphoid organs. Once stimulated, the resulting effector cells interact with APC in peripheral tissues. To this end, T cells must migrate to discrete sites throughout the body where antigen may be found. Recent progress in the field has revealed that the migratory abilities of T cells are critically dependent on their differentiation state, which is shaped by a multitude of factors. Thus, naive T cells are normally restricted to recirculate between the blood and secondary lymphoid tissues, although in some autoimmune diseases they may also accumulate in chronically inflamed tissues. When CD8(+) T cells encounter antigen and differentiate into short-lived effector CTL, they lose the ability to home to lymph nodes but gain access to peripheral tissues and sites of inflammation. Long-lived memory cells exist in (at least) two flavors: central memory cells that migrate to both lymphoid organs and peripheral sites of inflammation, and effector memory cells that are preferentially localized in non-lymphoid tissues. Our current understanding of the interplay of T cell differentiation and migration has been boosted by the development of T-GFP mice, in which transgenic green fluorescent protein is expressed selectively in naive and central memory T cells, but not in effector cytotoxic T cells (CTL). This review will focus on recent studies in which T-GFP mice were used to dissect the traffic signals for naive T cell homing to secondary lymphoid organs, the factors that influence the differentiation of naive CD8(+) T cells into cytotoxic and memory cells, as well as the in vivo trafficking routes of antigen-experienced subsets. 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 Pediat, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008; OI Weninger, Wolfgang/0000-0003-3133-8699 FU NHLBI NIH HHS [HL54936, HL56949, HL62524] NR 64 TC 85 Z9 87 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2002 VL 186 BP 221 EP 233 DI 10.1034/j.1600-065X.2002.18618.x PG 13 WC Immunology SC Immunology GA 594HE UT WOS:000178043100018 PM 12234374 ER PT J AU Bruss, JB Siber, GR AF Bruss, JB Siber, GR TI Quantitative priming with inactivated pertussis toxoid vaccine in the aerosol challenge model SO INFECTION AND IMMUNITY LA English DT Article ID CELL-MEDIATED-IMMUNITY; BORDETELLA-PERTUSSIS; WHOLE-CELL; RESPIRATORY-INFECTION; FILAMENTOUS HEMAGGLUTININ; CONTROLLED TRIAL; TH1 CELLS; MICE; CHILDREN; TOXIN AB Serum antibodies to pertussis toxin (PT) have been shown to be protective against severe pertussis disease, although a specific level of anti-PT antibody that correlates with protection has not been demonstrated. Current animal models such as the intracerebral challenge model have significant limitations in correlating protection to a specific level of anti-PT antibody. This study examines the protective effects of priming with tetranitromethane-inactivated pertussis toxoid (PTx) vaccine in the aerosol challenge model and whether a measurable response to a priming dose of PTx is enough to initiate a protective secondary response when challenged with infection. The correlation of priming with markers of illness such as leukocytosis, weight loss, bacterial proliferation, and mortality after established infection with Bordetella pertussis was explored. BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. Data were analyzed according to the primary immunologic response, differentiating responders (anti-PT immunoglobulin G [IgG] greater than or equal to1 mug/ml) from nonresponders (anti-PT IgG <1 mug/ml). Mice that showed evidence of priming on the day of aerosol challenge were able to mount a secondary response to the challenge with a greater than or equal to2-fold rise in anti-PT IgG antibody by day 7 and a greater than or equal to10-fold rise by day 14 post-aerosol challenge. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Bruss, JB (reprint author), Pharmacia Corp, Clin Res Infect Dis, 7000 Portage Rd, Kalamazoo, MI 49001 USA. NR 48 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2002 VL 70 IS 8 BP 4600 EP 4608 DI 10.1128/IAI.70.8.4600-4608.2002 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 574VC UT WOS:000176909400071 PM 12117973 ER PT J AU Mylonakis, E Engelbert, M Qin, X Sifri, CD Murray, BE Ausubel, FM Gilmore, MS Calderwood, SB AF Mylonakis, E Engelbert, M Qin, X Sifri, CD Murray, BE Ausubel, FM Gilmore, MS Calderwood, SB TI The Enterococcus faecalis fsrB gene, a key component of the fsr quorum-sensing system, is associated with virulence in the rabbit endophthalmitis model SO INFECTION AND IMMUNITY LA English DT Article ID STAPHYLOCOCCUS-AUREUS; RESISTANT ENTEROCOCCI; SERINE-PROTEASE; GELATINASE AB We used a rabbit endophthalmitis model to explore the role of fsrB, a gene required for the function of the fsr quorum-sensing system of Enterococcus faecalis, in pathogenicity. A nonpolar deletion mutant of fsrB had significantly reduced virulence compared to wild type. Complementation of mutation restored virulence. These data corroborate the role of fsrB in E. faecalis pathogenesis and suggest that the rabbit endophthalmitis model can be used to study the in vivo role of quorum sensing. C1 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. Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73190 USA. Univ Texas, Div Infect Dis, Houston, TX 77030 USA. Univ Texas, Ctr Study Emerging & Reemerging Pathogens, Houston, TX 77030 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NEI NIH HHS [EY08289, EY12190, R01 EY008289, P30 EY012190]; NIAID NIH HHS [AI41108, R01 AI047923, AI47923, R01 AI041108, R37 AI047923] NR 21 TC 57 Z9 62 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2002 VL 70 IS 8 BP 4678 EP 4681 DI 10.1128/IAI.70.8.4678-4681.2002 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 574VC UT WOS:000176909400080 PM 12117982 ER PT J AU Zahedi, K Prada, AE Mulligan, A Prada, JA Davis, AE AF Zahedi, K Prada, AE Mulligan, A Prada, JA Davis, AE TI Normal transcription of the C1 inhibitor gene is dependent upon a polypurine center dot polypyrimidine region within the promoter SO INFLAMMATION LA English DT Article DE complement; C1 inhibitor; transcription; promoter ID LIVER-SPECIFIC TRANSCRIPTION; ESCHERICHIA-COLI-CELLS; ZINC-FINGER PROTEIN; MYC GENE; STIMULATING FACTOR; INITIATOR ELEMENT; NUCLEAR FACTOR; TRIPLEX DNA; START SITE; IN-VIVO AB Analysis of the transcriptional activity of C1 inhibitor (C1INH) promoter reporter constructs with mutations in the R.Y region indicate that triplex formation by this region is not a predictor of transcriptional activity and that normal promoter function depends on the interaction of trans acting factors with specific elements within this region. Electrophoretic mobility shift assay (EMSA) of Hep3B nuclear extracts using the wild type promoter probe (nucleotides -98 to -9) yielded four major bands. Incubation of the same extracts with probes lacking the HNF-1 site resulted in the disappearance of one band. Supershift assays indicate that HNF-1alpha is the only previously identified protein that is present in the EMSA bands. Southwestern blot analysis detected four bands (M-r's similar to130, 75, 65 and 20 kDa). These data suggest that the -98 to -9 region of the C1INH promoter interacts with at least four proteins, one of which is HNF-1alpha. C1 Childrens Hosp Fdn, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Zahedi, K (reprint author), Childrens Hosp Fdn, Div Nephrol & Hypertens, 3333 Burnet Ave, Cincinnati, OH 45229 USA. FU NICHD NIH HHS [HD22082, HD33727] NR 42 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-3997 J9 INFLAMMATION JI Inflammation PD AUG PY 2002 VL 26 IS 4 BP 183 EP 191 AR UNSP 0360-3997/02/0800-0183/0 DI 10.1023/A:1016519813252 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 576YY UT WOS:000177035800006 PM 12184632 ER PT J AU Kacmarek, RM AF Kacmarek, RM TI A workable alternative to the problems with tracheal gas insufflation? SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS SYNDROME; INDUCED LUNG INJURY; PERMISSIVE HYPERCAPNIA; EXPIRATORY PHASE; PRESSURE CONTROL; VENTILATION; MORTALITY; ACIDOSIS; MODEL C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 17 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 AUG PY 2002 VL 28 IS 8 BP 1009 EP 1011 DI 10.1007/s00134-002-1343-1 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 641HK UT WOS:000180739200003 PM 12398089 ER PT J AU Ellisen, LW AF Ellisen, LW TI Regulation of gene expression by WT1 in development and tumorigenesis SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE WT1; Wilms tumor; tumor suppressor; transcription factor; hematopoiesis ID TUMOR-SUPPRESSOR GENE; DENYS-DRASH SYNDROME; WILMS-TUMOR; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; SUBNUCLEAR LOCALIZATION; MUTANT PROTEINS; TARGET GENE; PRODUCT; GROWTH AB WT1 encodes a zinc finger transcription factor implicated in normal development and tumorigenesis. Germline mutation or deletion of WT1 results in a spectrum of abnormal kidney development, male-to-female intersex disorders, and predisposition to pediatric nephroblastoma, Wilms tumor. Initially thought to encode a transcriptional repressor, WT1-dependent functions are now more clearly linked to its property as a transcriptional activator of genes involved in renal development and sex determination. WT1 is expressed in 4 isoforms as a result of 2 alternative messenger RNA splicing events, the more significant of which encodes the 3 amino acids lysine, threonine, and serine (KTS) between zinc fingers 3 and 4. Although WT1 isoforms lacking KTS act as sequence-specific DNA binding factors, a large body of evidence now implicates the KTS-containing isoforms in RNA processing. In keeping with distinct biochemical mechanisms for these isoforms, genetic data from humans and mice point to separate but partially overlapping roles for WT1 (+KTS) and (-KTS) during genitourinary development. Recently, a hematopoietic model system has been used to study functional properties of WT1 in vitro. WT1 expression in primary hematopoietic cells leads to stage-specific effects that may be relevant to WT1-mediated tumor suppression. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ-904,55 Fruit St, Boston, MA 02114 USA. NR 53 TC 18 Z9 23 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD AUG PY 2002 VL 76 IS 2 BP 110 EP 116 DI 10.1007/BF02982572 PG 7 WC Hematology SC Hematology GA 588FT UT WOS:000177692000002 PM 12215008 ER PT J AU Munshi, NC Hideshima, T Chauhan, D Richardson, P Anderson, KC AF Munshi, NC Hideshima, T Chauhan, D Richardson, P Anderson, KC TI Novel biologically based therapies for multiple myeloma SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article; Proceedings Paper CT 29th Wolrd Congress of the International-Society-of-Hematology CY 2002 CL SEOUL, SOUTH KOREA SP Int Soc Hematol ID DRUG-RESISTANCE; THALIDOMIDE; CELLS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. NR 12 TC 8 Z9 8 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD AUG PY 2002 VL 76 SU 1 BP 340 EP 341 PG 2 WC Hematology SC Hematology GA 611FM UT WOS:000179005800060 PM 12430878 ER PT J AU Troulis, MJ Everett, R Seldin, EB Kikinis, R Kaban, LB AF Troulis, MJ Everett, R Seldin, EB Kikinis, R Kaban, LB TI Development of a three-dimensional treatment planning system based on computed tomographic data SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the American-Cleft-Palate-Craniofacial-Association CY APR 26, 2001 CL MINNEAPOLIS, MINNESOTA SP Amer Cleft Palate Crainofacial Assoc DE treatment planning; 3D; CT data ID DISTRACTION DEVICE; MODEL AB Current surgical treatment planning systems predict three-dimensional (3D) corrections from two-dimensional (2d) data and are inadequate for complex movements. In this paper, we present a 3D planning system based on computed tomographic (CT) data. A three-dimensional CT scan of the craniofacial skeleton forms the database. Software developed in the Harvard Surgical Planning Laboratory was modified for the craniofacial skeleton. Reproducible skeletal landmarks are identified for superimposition. A 'cutting tool' is used to segment the mandible and segments are moved to their predicted positions. A 'collision tool', alerts the operator of skeletal interferences. An analysis of selected scans is used to demonstrate the system. Three-dimensional visualization of the facial skeleton, selection of landmarks, measurement of angles and distances, simulation of osteotomies, repositioning of bones, detection of collisions and super-imposition of scans were accomplished. In an illustrative case of HeMifacial Microsomia, predicted and actual 3D corrective movements of the entire mandible were documented. Analysis of scans indicated that 3D planning can prevent insufficient jaw lengthening or other surgical inaccuracies which occur with standard 2D methods. Software demonstrated here will allow the surgeon to accurately plan treatment and evaluate craniomaxillofacial surgery outcomes. Future applications may include surgical navigation. C1 Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Surg Treatment Planning Lab, Boston, MA USA. RP Troulis, MJ (reprint author), Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Dent Med, Massachusetts Gen Hosp, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. NR 24 TC 93 Z9 98 U1 2 U2 13 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD AUG PY 2002 VL 31 IS 4 BP 349 EP 357 DI 10.1054/ijom.2002.0278 PG 9 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 591TD UT WOS:000177895600002 PM 12361065 ER PT J AU Hurwitz, MD Schnieder, L Manola, J Beard, CJ Kaplan, ID D'Amico, AV AF Hurwitz, MD Schnieder, L Manola, J Beard, CJ Kaplan, ID D'Amico, AV TI Lack of radiation dose response for patients with low-risk clinically localized prostate cancer: A retrospective analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; radiation; dose ID ESCALATION; LESS-THAN-OR-EQUAL-TO-10; THERAPY AB Purpose: The need for dose escalation for patients with low-risk clinically localized prostate cancer remains controversial. In this study, we report our pooled institutional experience of low-risk patients treated with a range of "standard" radiation doses to assess outcome in regard to biochemical failure and to determine whether a dose-response relationship exists within this conventional dose range. Methods and Materials: Patients with low-risk clinically localized prostate cancer (T1 or T2a. Gleason grade less than or equal to6, and prostate-specific antigen less than or equal to10 ng/mL) treated at Joint Center for Radiation Therapy-affiliated institutions between October 1989 and September 1997 were retrospectively analyzed for freedom from biochemical failure. The dose was prescribed volumetrically with 95% normalization to between 5760 and 6900 cGy (6100 and 7300 cGy ICRU reference point dose). Patients were stratified into 3 groups with relatively equal numbers of patients (<6660, 6660, and >6660 cGy). To ensure that any differences in biochemical failure between patients at the lower and higher ends of the dose range used were not masked by analysis of the entire cohort, patients receiving less than or equal to6500 cGy or greater than or equal to6800 cGy were subsequently analyzed separately. Biochemical failure was defined per the ASTRO consensus definition. The log-rank test was used to assess for differences in follow-up and time to biochemical failure. A Kaplan-Meier plot of time to biochemical failure for the initial 3 subgroups was generated. Results: A total of 264 patients were identified. Sixteen patients whose dose was not recorded in the database were excluded from analysis. The median follow-up was 35 months. No significant differences were found in baseline prostate-specific antigen, Gleason grade, or clinical stage among the groups. The overall actuarial rate of 5-year freedom from biochemical failure was 80.2%. By dose level, the 5-year biochemical failure-free rate was 79.2%, 78.4%, and 84.5% for <6660 cGy, 6660 cGy, and >6660 cGy, respectively. These differences were not significant. Subsequently, 45 patients receiving less than or equal to6500 cGy were compared with 23 patients receiving greater than or equal to6800 cGy. The difference between these groups was not significant. The 5-year freedom from biochemical failure rate for the patients receiving less than or equal to6500 cGy was 89.9%. Conclusion: Within a range of doses considered standard for treatment of low-risk clinically localized prostate cancer during an 8-year period, no improvement in biochemical freedom from failure was noted with the higher doses. The overall 5-year rate of freedom from biochemical failure is consistent with that reported by others with standard and escalated external beam doses used in this low-risk population. A prospective randomized study is necessary to define the optimal dose in this patient population. (C) 2002 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Hurwitz, MD (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI,L2, Boston, MA 02115 USA. NR 12 TC 13 Z9 13 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 AUG 1 PY 2002 VL 53 IS 5 BP 1106 EP 1110 AR PII S0360-3016(02)02885-7 DI 10.1016/S0360-3016(02)02885-7 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 580CV UT WOS:000177217800002 PM 12128108 ER PT J AU Zietman, A Thakral, H Skowronski, U Shipley, W AF Zietman, A Thakral, H Skowronski, U Shipley, W TI Freedom from castration: An alternative end point for men with localized prostate cancer treated by external beam radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; radiotherapy; androgen deprivation; watchful waiting ID ANDROGEN DEPRIVATION THERAPY; CONSERVATIVE MANAGEMENT; RADICAL PROSTATECTOMY; NATURAL-HISTORY; PSA; PROGRESS; SURVIVAL AB Purpose: Androgen deprivation therapy (ADT) is frequently given to men with localized prostate cancer. This study was designed to determine what proportion of men require subsequent ADT if their localized prostate cancer is first treated by radiation. Methods and Materials: A retrospective review of the outcome of 768 men with T1-4NxM0 prostate cancer treated with external beam radiation at a single institution from 1988 to 1995. The median follow-up for the entire group was 5.8 years. The end points analyzed were biochemical failure (3 successive rises in prostate-specific antigen) and ADT (either medical or surgical castration). Results: A total of 322 biochemical failure events occurred among the 768 treated patients, and 187 began ADT during the period of observation. Fifty-four percent of men starting ADT did so without rebiopsy or radiographic evidence of persistent disease. The overall freedom from biochemical failure rate at 10 years was 43.3% and the 10-year freedom from ADT rate was 56.3%. The corresponding values for the most favorable subgroup (T1-2a, Gleason sum 6. prostate-specific antigen less than or equal to10 ng/mL) were 61.8% and 72.8%. Conclusions: Curative therapy Is often given to men with prostate cancer and a life expectancy of < 10 years, even when a survival gain is not expected. One new measure of its value, if any, may be its efficacy in preventing a subsequent, potentially more morbid, therapy such as ADT. The results of this study showed that most men with early-stage prostate cancer do avoid ADT in the 10 years after radiation therapy. This rate is less than that seen in the few contemporary watchful-waiting series. (C) 2002 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM azietman@partners.org NR 27 TC 3 Z9 3 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 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2002 VL 53 IS 5 BP 1152 EP 1159 AR PII S0360-3016(02)02858-4 DI 10.1016/S0360-3016(02)02858-4 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 580CV UT WOS:000177217800009 PM 12128115 ER PT J AU Chen, CC Chang, JH Lee, JB Javier, J Azar, DT AF Chen, CC Chang, JH Lee, JB Javier, J Azar, DT TI Human corneal epithelial cell viability and morphology after dilute alcohol exposure SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PHOTOREFRACTIVE KERATECTOMY; EXCIMER-LASER; MUCOSAL APOPTOSIS; PRIMARY CULTURES; FACTOR-ALPHA; IN-VITRO; ETHANOL; REMOVAL; DEATH; EXPRESSION AB PURPOSE. To determine the effect of dilute alcohol on human corneal epithelial Cellular morphology and viability. Dilute alcohol is used for epithelial removal during photorefractive keratectomy (PRK) and laser subepithelial keratomileusis (LASEK). METHODS. Corneal epithelial sheets harvested from human eyes after alcohol application during PRK were examined by light and electron microscopy (specimens I-IV). In addition, tissue cultures of human epithelial sheets were monitored for epithelial migration and attachment (specimens V-VII). To determine the effect of dilute alcohol on epithelial cell viability, simian virus (SV)40-immortalized human corneal epithelial cells were exposed to dilute alcohol in distilled water (EtOH-H2O) or to keratinocyte serum-free medium (EtOH-KSFM) for incubation periods of 20 to 45 seconds and concentrations of 10% to 70%. Cell membrane permeability and intracellular esterase activity were analyzed by calcein-acetoxymethyl ester (AM)/ethidium homodimer assay, TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect apoptotic cells at 0, 8,12,24, and 72 hours. RESULTS. Electron microscopy showed varying degrees of basement membrane alterations after alcohol application, including disruptions, discontinuities, irregularities, and duplication (specimens I-IV). Cellular destruction and vacuolization of basal epithelial cells associated with absent basement membrane were also observed (specimen III). One of three cultured epithelial sheets showed attachment and outgrowth in the tissue culture until day 15 (specimen V). Twenty-second exposure of cultured immortalized human cells to various concentrations of EtOH-H2O showed significant reduction of viable cells when EtOH-H2O concentration exceeded 25% (P = 0.005). Increasing the duration of application of 20% EtOH-H2O beyond 30 seconds resulted in a significant reduction in viable cells (69.69% +/- 16.34% at 30 seconds compared with 2.14% +/- 2.29%, 10.45% +/- 7.11%, and 11.09% +/- 15.73% at 35, 40, and 45 seconds, respectively; P = 0.01), TUNEL assay of cultured human corneal epithelial cells exposed to 20%. EtOH-H2O for 20 and 40 seconds showed maximal labeling at 24 hours (58.05% +/- 33.10%) and 8 hours (94.12% +/- 1.21%), respectively, Exposure to 20% EtOH-KSFM for 20 and 40 seconds resulted in substantially lower TUNEL positivity (3.51% +/- 0.20% at 24 hours and 7.11% +/- 0.49% at 8 hours). CONCLUSIONS. The viability and electron microscopic findings in the basement membrane zone showed significant variation after treatment of the epithelium in vivo with dilute alcohol. The application of dilute alcohol on the monolayer of cultured corneal epithelial cells resulted in increasing cell death in a dose- and time-dependent manner. C1 Massachusetts Eye & Ear Infirm, Corncal 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, Corncal External Dis & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY10101] NR 46 TC 83 Z9 98 U1 2 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2002 VL 43 IS 8 BP 2593 EP 2602 PG 10 WC Ophthalmology SC Ophthalmology GA 577ZZ UT WOS:000177094100013 PM 12147590 ER PT J AU Clancy, SA McNally, RJ Schacter, DL Lenzenweger, MF Pitman, RK AF Clancy, SA McNally, RJ Schacter, DL Lenzenweger, MF Pitman, RK TI Memory distortion in people reporting abduction by aliens SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID CHILDHOOD SEXUAL ABUSE; FALSE RECOGNITION; COGNITIVE NEUROSCIENCE; ILLUSIONS; SCHIZOTYPY; SCALE; WOMEN; SUSCEPTIBILITY; SCHIZOPHRENIA; DISSOCIATION AB False memory creation was examined in people who reported having recovered memories of traumatic events that are unlikely to have occurred: abduction by space aliens. A variant of the Deese/Roediger-McDermott paradigm (J. Deese, 1959; H. L. Roediger III & K. B. McDermott, 1995) was used to examine false recall and false recognition in 3 groups: people reporting recovered memories of alien abduction, people who believe they were abducted by aliens but have no memories, and people who deny having been abducted by aliens. Those reporting recovered and repressed memories of alien abduction were more prone than control participants to exhibit false recall and recognition. The groups did not differ in correct recall or recognition. Hypnotic suggestibility, depressive symptoms, and schizotypic features were significant predictors of false recall and false recognition. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Clancy, SA (reprint author), Harvard Univ, Dept Psychol, 1232 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [MH61268]; PHS HHS [NIA08441] NR 51 TC 70 Z9 70 U1 2 U2 30 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 2002 VL 111 IS 3 BP 455 EP 461 DI 10.1037//0021-843X.111.3.455 PG 7 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 575QX UT WOS:000176960100005 PM 12150421 ER PT J AU Seage, GR Losina, E Goldie, SJ Paltiel, AD Kimmel, AD Freedberg, KA AF Seage, GR Losina, E Goldie, SJ Paltiel, AD Kimmel, AD Freedberg, KA TI The relationship of preventable opportunistic infections, HIV-1 RNA, and CD4 cell counts to chronic mortality SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1 mortality; opportunistic infections; HIV-1 RNA; CD4 cell counts ID PNEUMOCYSTIS-CARINII PNEUMONIA; IMMUNODEFICIENCY-VIRUS DISEASE; COMBINATION ANTIRETROVIRAL THERAPY; MARGINAL STRUCTURAL MODELS; PLASMA VIRAL LOAD; BACTERIAL PNEUMONIA; COST-EFFECTIVENESS; IMMUNE ACTIVATION; T-CELLS; AIDS AB Background: Both HIV-1 RNA and absolute CD4 cell counts have been identified as important predictors of HIV-1 disease progression and mortality. The independent impact of opportunistic infections on the risk of chronic mortality, defined as death beyond 30 days of an opportunistic infection, has not been studied when controlling for HIV-1 RNA. Our objective was to determine the relationship between a history of any of five preventable opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex, toxoplasmosis, cytomegalovirus, and candida esophagitis) and chronic mortality. Methods: Using the Multicenter AIDS Cohort Study (MACS) public use data set of 2193 HIV-infected men in four U.S. cities, we employed a Cox regression model to estimate the impact of a history of preventable opportunistic infection on chronic mortality while controlling for maximum HIV-1 RNA, CD4 cell count, use of anti-retroviral drugs, and age. Findings: The chronic mortality rate among individuals with a history of preventable opportunistic infection was 66.7 per 100 person-years compared with 2.3 per 100 person-years for those without a history of preventable opportunistic infection (RR = 28.4, 95% CI: 24.7-32.8). In the adjusted analysis, the relative hazard of death for those with a history of preventable opportunistic infections was 7.0 (5.8-8.3), whereas antiretroviral therapy was associated with a decreased risk of death (0.37 [0.30-0.44]). We found no association between maximum HIV-1 RNA and chronic mortality. There was statistically significant effect modification between preventable opportunistic infections and CD4 cell count (P < .0001). Interpretation: Preventable opportunistic infections cause not only short-term mortality in HIV-1 disease but appear to have a major impact on chronic mortality. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Yale Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Seage, GR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. FU AHRQ HHS [HS07317]; NCRR NIH HHS [M01 RR000722, 5-M01-RR00722]; NIAID NIH HHS [R01 AI42006, P30 AI042851, IP30 AI42851, U01-AI-35039, U01 AI037613, U01-AI-37613, U01-AI-35042, U01-AI-35040, U01 AI035043, U01-AI-37948, R01 AI042006, U01 AI037984, U01-AI-35043, U01-AI-35041] NR 47 TC 29 Z9 29 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD AUG 1 PY 2002 VL 30 IS 4 BP 421 EP 428 DI 10.1097/01.QAI.0000021700.48448.69 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 578WV UT WOS:000177144800007 PM 12138349 ER PT J AU Quinn, DA Moufarrej, RK Volokhov, A Hales, CA AF Quinn, DA Moufarrej, RK Volokhov, A Hales, CA TI Interactions of lung stretch, hyperoxia, and MIP-2 production in ventilator-induced lung injury SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE neutrophils; cytokines; rat ventilation; macrophage inflammatory protein-2 ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; PEAK AIRWAY PRESSURES; MECHANICAL VENTILATION; PULMONARY-EDEMA; TRACHEAL INSUFFLATION; CYTOKINE RELEASE; RAT LUNGS; IN-VITRO; EXPRESSION AB The use of positive pressure mechanical ventilation can cause ventilator-induced lung injury (VILI). We hypothesized that hyperoxia in combination with large tidal volumes (VT) would accentuate noncardiogenic edema and neutrophil infiltration in VILI and be dependent on stretch-induced macrophage inflammatory protein-2 (MIP-2) production. In rats ventilated with VT 20 ml/kg, there was pulmonary edema formation that was significantly increased by hyperoxia. Total lung neutrophil infiltration and MIP-2 in bronchoalveolar lavage (BAL) fluid were significantly elevated, in animals exposed to high VT both on room air (RA) and with hyperoxia. Hyperoxia markedly augmented the migration of neutrophils into the alveoli. Anti-MIP-2 antibody blocked migration of neutrophils into the alveoli in RA by 51% and with hyperoxia by 65%. We concluded that neutrophil migration into the alveoli was dependent on stretch-induced MIP-2 production. Hyperoxia significantly increased edema formation and neutrophil migration into the alveoli with VT 20 ml/kg, although BAL MIP-2 levels were nearly identical to VT 20 ml/kg with RA, suggesting that other mechanisms may be involved in hyperoxia-augmented neutrophil alveolar content in VILI. C1 Massachusetts Gen Hosp, Pulm Crit Care Univ, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Quinn, DA (reprint author), Massachusetts Gen Hosp, Pulm Crit Care Univ, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. FU NHLBI NIH HHS [K08 HL-03920-01, HL-39150] NR 48 TC 111 Z9 122 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 2002 VL 93 IS 2 BP 517 EP 525 DI 10.1152/japplphysiol.00570.2001 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 575GY UT WOS:000176939600016 PM 12133859 ER PT J AU Zou, LL Yotnda, T Zhao, TJ Yuan, XQ Long, Y Zhou, HS Yang, KY AF Zou, LL Yotnda, T Zhao, TJ Yuan, XQ Long, Y Zhou, HS Yang, KY TI Reduced inflammatory reactions to the inoculation of helper-dependent adenoviral vectors in traumatically injured rat brain SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE adenovirus; helper-dependent; transgene; immune response; brain; trauma ID TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; LECITHINIZED SUPEROXIDE-DISMUTASE; CONTROLLED CORTICAL IMPACT; HUMORAL IMMUNE-RESPONSES; MEDIATED GENE-TRANSFER; LONG-TERM EXPRESSION; IN-VIVO; FACTOR-ALPHA; RECOMBINANT ADENOVIRUS AB Traumatic brain injury (TBI) causes delayed neuronal deficits that in principle could be prevented by timely intervention with therapeutic genes. However. appropriate vectors for gene transfer to the brain with TBI remain to be developed. First-generation adenoviruses (fgAd) are usually associated with inflammatory and toxic effects when inoculated into brains, despite their high efficiency of gene transfer to these tissues. In this study the authors attempted to determine whether a less immunogenic gene-transfer protocol can be established in the traumatically injured rat brain using helper-dependent adenoviruses (hdAd), a novel adenoviral construct with full deletion of viral coding sequences. Their results show that transgene expression from intrahippocampally inoculated hdAd is maintained for at least 2 months after TBI, in contrast to the much shorter duration of fgAd-mediated gene expression. There was only minimal secretion of proinflammatory IL-1beta and TNF-alpha after inoculation of hdAd. Furthermore, the hdAd-mediated gene expression was associated with less microglial proliferation. astrocytic activation, and macrophage infiltration than observed in fgAd-inoculated brains. There was no additional tissue loss after hdAd inoculation compared with PBS injection. Although both anti-adenoviral and neutralizing antibodies were found in serum after brain inoculation of hdAd, they did not appear to affect transgene expression. The results suggest that hdAd are less immunogenic vectors than conventional adenoviral vectors. and offer improved vehicles for long-term therapeutic transgene transfer to traumatically injured brains. C1 Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Neurol Care Line, Houston, TX USA. RP Yang, KY (reprint author), Baylor Coll Med, Dept Neurosurg, 1 Baylor Plaza, Houston, TX 77030 USA. FU NINDS NIH HHS [R01-NS35502-03] NR 67 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2002 VL 22 IS 8 BP 959 EP 970 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 579PL UT WOS:000177187000007 PM 12172381 ER PT J AU Misra, M MacLaughlin, DT Donahoe, PK Lee, MM AF Misra, M MacLaughlin, DT Donahoe, PK Lee, MM TI Measurement of Mullerian inhibiting substance facilitates management of boys with microphallus and cryptorchidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERUM LEVELS; PREPUBERTAL BOYS; SERTOLI CELLS; DUCT SYNDROME; LEYDIG-CELLS; HORMONE; TESTOSTERONE; CHILDREN; IMMUNOASSAY; STIMULATION AB Mullerian inhibiting substance (MIS) is a gonadal hormone expressed in a sexually dimorphic pattern. In males, serum MIS reflects Sertoli cell function and provides an estimate of seminiferous tubular integrity. We examined the role of MIS determination in the evaluation of boys with microphallus (n = 62) and/or cryptorchidism (n = 156). MIS was normal in 69.2% of boys with isolated microphallus compared with 38.1% of boys with microphallus and coexisting cryptorchidism (P < 0.05). In the cryptorchid group, MIS was normal in 46.8%, low in 24.4%, and absent in 28.8%. Normal values for age were associated with testicular tissue, whereas undetectable values were indicative of anorchia, except for two boys with MIS gene mutations (persistent Mullerian duct syndrome). These data demonstrated that a basal MIS measurement is more specific and has a higher positive predictive value than stimulated testosterone values for ascertaining the absence of testes (anorchia). In summary, a normal serum MIS concentration in the prepubertal child is a reliable determinant of testicular tissue, whereas an undetectable value is a highly sensitive initial screening test for anorchia. We conclude that preoperative measurement of MIS facilitates the management of children with cryptorchidism and intersex disorders and offers a measure of Sertoli cell function. C1 Duke Univ, Med Ctr, Pediat Enocrine Div, Durham, NC 27710 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee, MM (reprint author), Duke Univ, Med Ctr, Pediat Enocrine Div, Box 3080,Bell Bldg, Durham, NC 27710 USA. EM lee00140@mc.duke.edu OI Lee, Mary/0000-0002-7204-4884 FU NCI NIH HHS [CA-17393]; NICHD NIH HHS [HD-31223, HD-36768]; NIDDK NIH HHS [DK-07703]; PHS HHS [D-01367] NR 40 TC 34 Z9 39 U1 0 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 AUG PY 2002 VL 87 IS 8 BP 3598 EP 3602 DI 10.1210/jc.87.8.3598 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 581HG UT WOS:000177285400014 PM 12161481 ER PT J AU Mittan, D Lee, S Miller, E Perez, RC Basler, JW Bruder, JM AF Mittan, D Lee, S Miller, E Perez, RC Basler, JW Bruder, JM TI Bone loss following hypogonadism in men with prostate cancer treated with GnRH analogs SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; HORMONE REPLACEMENT THERAPY; MINERAL DENSITY; BIOCHEMICAL MARKERS; OSTEOPOROSIS; ORCHIECTOMY; CARCINOMA; TURNOVER; METASTASES; MENOPAUSE AB It is known that bone mineral density (BMD) is low in men who are hypogonadal. However, the rate and sites of bone loss following testosterone deficiency are not known. The resulting hypogonadism after GnRH analog therapy for the treatment of prostate cancer allows us to examine bone loss and bone resorption immediately after testosterone withdrawal. Therefore, we examined the effects of GnRH analog treatment on bone loss and bone resorption in men with prostate cancer. BMD and serum and urine concentrations of markers of bone turnover were determined in men with prostate cancer and in age-matched controls. Measurements were taken before GnRH therapy and 6 and 12 months after instituting therapy. After 12 months of GnRH therapy, the BMD of the total hip and ultra distal radius decreased significantly (P < 0.001) in men with prostate cancer compared with the controls. The mean bone loss was 3.3% and 5.3%, respectively. The observed reduction in BMD in the spine (2.8%) and the femoral neck (2.3%) did not reach statistical significance. No significant bone loss was observed in the control subjects. The concentration of the urine marker of bone resorption, N-telopeptide, was significantly increased from baseline and from controls at both 6 and 12 months in patients treated with GnRH analog therapy compared with control subjects (P < 0.05). The concentration of a serum marker of bone formation, bone-specific alkaline phosphatase, was not significantly different from baseline or from controls at 6 and 12 months. Thus, the decreased total hip and ultra distal radius BMI) and increased urinary N-telopeptide concentration after testosterone withdrawal demonstrate an increase in trabecular bone loss and enhanced bone resorption. These findings demonstrate a significant loss of bone in men with prostate cancer after receiving GnRH therapy and suggest that the total hip and radius are the preferred sites for monitoring bone loss in older men. In addition, markers of bone resorption may be helpful. C1 Univ Texas, Hlth Sci Ctr, Div Endocrinol, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. Vet Affairs Med Ctr, Dept Res & Dev, San Antonio, TX 78229 USA. RP Bruder, JM (reprint author), Univ Texas, Hlth Sci Ctr, Div Endocrinol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM bruder@uthscsa.edu NR 29 TC 150 Z9 157 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2002 VL 87 IS 8 BP 3656 EP 3661 DI 10.1210/jc.87.8.3656 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 581HG UT WOS:000177285400022 PM 12161491 ER PT J AU Layman, LC Porto, ALA Xie, J da Motta, LACR DA Motta, LDC da Motta, LDC Weiser, W Sluss, PM AF Layman, LC Porto, ALA Xie, J da Motta, LACR DA Motta, LDC da Motta, LDC Weiser, W Sluss, PM TI FSH beta gene mutations in a female with partial breast development and a male sibling with normal puberty and azoospermia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; SUBUNIT GENE; HYPOGONADISM; RECEPTOR; DEFICIENCY; BIOASSAY AB FSH is a dimeric pituitary glycoprotein hormone that regulates gonadal function. Human mutations in the FSHbeta gene have been shown to produce complete deficiency states in which pubertal development and reproductive capacity are inhibited. To date, no patients with partial or complete pubertal development due to FSHbeta mutations have been documented in humans. We describe and characterize affected siblings, a male and a female, with evidence of pubertal development due to homozygosity for a Tyr76X nonsense mutation in the FSHbeta gene. In vitro analysis of this mutant demonstrates unmeasurable FSH by immunoassay and by two different bioassays, using either cAMP (homologous FSH bioassay) or estradiol (rat granulosa. cell assay) as the endpoints. In additional in vitro analyses, mutants previously found in patients with a phenotype of complete FSH deficiency (Cys51Gly and Val61X) and the Tyr76X were compared in the same immuno- and bioassays. All mutations failed to produce measurable FSH by all assays. Unexpectedly, these siblings with isolated FSH deficiency due to a nonsense FSHbeta mutation had some evidence of puberty, suggesting that other factors might preserve gonadal steroidogenesis in the absence of FSH or that current bioassays cannot discriminate among very low FSH levels. C1 Med Coll Georgia, Sect Reprod Endocrinol Infertil & Genet, Dept Obstet & Gynecol, Augusta, GA 30912 USA. Med Coll Georgia, Neurobiol Program, Inst Mol Med & Genet, Augusta, GA 30912 USA. Univ Brasilia, Dept Med, Endocrinol Sect, BR-71525 Brasilia, DF, Brazil. Abbott Pharmaceut Co, Abbott Pk, IL 60664 USA. Univ Brasilia, Dept Obstet & Gynecol, Sect Reprod Endocrinol, Brasilia, DF, Brazil. Serono, Rockland, MA 02370 USA. Massachusetts Gen Hosp, Reprod Endocrine Lab Unit, Boston, MA 02114 USA. RP Layman, LC (reprint author), Med Coll Georgia, Sect Reprod Endocrinol Infertil & Genet, Dept Obstet & Gynecol, 1120 15th St, Augusta, GA 30912 USA. EM Llayman@mail.mcg.edu RI Lofrano Porto, Adriana/H-8348-2012 OI Lofrano Porto, Adriana/0000-0002-9590-1631 FU NICHD NIH HHS [HD29164, HD33004] NR 16 TC 69 Z9 73 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2002 VL 87 IS 8 BP 3702 EP 3707 DI 10.1210/jc.87.8.3702 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 581HG UT WOS:000177285400030 PM 12161499 ER PT J AU Egan, JM Meneilly, GS Habener, JF Elahi, D AF Egan, JM Meneilly, GS Habener, JF Elahi, D TI Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEPENDENT DIABETES-MELLITUS; RAT SKELETAL-MUSCLE; TURNOVER RATES; SENSITIVITY; RECEPTOR; AMIDE; GLP-1(7-36)AMIDE; SECRETION; KINETICS; HORMONE AB The insulinotropic hormone, glucagon-like peptide-1 (GLP-1), is being examined as a potential new agent for treatment in type 2 diabetic patients. Whereas the insulinotropic properties of this peptide are well established, another property of the hormone, an insulinomimetic effect per se, is controversial. In the normal glucose-tolerant lean state, it is difficult to demonstrate an insulinomimetic effect. The current study was conducted to examine whether GLP-1 has insulinomimetic effect in the obese state. Ten obese volunteers (body mass index, 34.6 +/- 0.8 kg/m(2)), whose ages were 32.5 +/- 3.0 yr, participated in two euglycemic clamp studies (n = 20 clamps) for 120 min. Five of the volunteers were females. The initial clamp was performed with a primed (0-10)-constant (10-60) infusion of GLP-1 at a final rate of 1.5 pmol (.) kg(-1) (.) min(-1). At 60 min, the GLP-1 infusion was terminated, and euglycemic was maintained from 60-120 min. After the GLP-1 study, each individual's plasma insulin level was measured. A second study was performed that was identical to the first, with the infusion of regular insulin in place of GLP-1. Insulin infusion rates were regulated in each individual to simulate plasma insulin levels produced during the GLP-1 infusion. The rate of disappearance of glucose was calculated for each subject. Fasting plasma insulin levels were similar between studies. In response to the GLP-1 infusion, with maintenance of plasma glucose level clamped at fasting level, significant increases in plasma insulin occurred in all subjects (P < 0.001). The insulin levels during the insulin infusion study were similar to that induced by GLP-1. The rate of disappearance of glucose (insulin-mediated glucose uptake) progressively increased in response to both the GLP-1 and insulin infusion. However, the rate of disappearance of glucose during the GLP-1 study was significantly higher (P = 0.033) than during the insulin study. We conclude that in insulin-resistant states, GLP-1 has insulinomimetic properties per se. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Geriatr Res Lab,Dept Med, Boston, MA 02114 USA. NIA, Diabet Sect, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. Univ British Columbia, Dept Med, Vancouver, BC V6T 1Z3, Canada. Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Elahi, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Geriatr Res Lab,Dept Med, Gray Bigelow Sub Basement 0015,55 Fruit St, Boston, MA 02114 USA. EM delahi@partners.org FU NCRR NIH HHS [M01-RR-02719]; NIA NIH HHS [AG-00599] NR 37 TC 79 Z9 82 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2002 VL 87 IS 8 BP 3768 EP 3773 DI 10.1210/jc.87.8.3768 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 581HG UT WOS:000177285400039 PM 12161508 ER PT J AU Lupien, SJ Wilkinson, CW Briere, S Kin, NMKNY Meaney, MJ Nair, NPV AF Lupien, SJ Wilkinson, CW Briere, S Kin, NMKNY Meaney, MJ Nair, NPV TI Acute modulation of aged human memory by pharmacological manipulation of glucocorticoids SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; CA1 PYRAMIDAL NEURONS; MINERALOCORTICOID RECEPTOR; HIPPOCAMPAL ATROPHY; CORTISOL-LEVELS; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; IN-VIVO; BRAIN; STRESS AB In a previous longitudinal study of basal cortisol levels and cognitive function in humans, we showed that elderly humans with 4- to 7-yr cumulative exposure to high levels of cortisol present memory impairments, compared with elderly humans with moderate cortisol levels over years. Here, we measured whether memory performance in two groups of elderly humans separated on the basis of their cortisol history over a 5-yr period could be modulated by a hormone-replacement protocol in which we inhibited cortisol secretion by the administration of metyrapone and then restored baseline cortisol levels by infusion of hydrocortisone. We showed that in elderly subjects with a 5-yr history of moderate cortisol levels (n = 8), metyrapone treatment significantly impaired memory performance, a deficit that was reversed following hydrocortisone replacement. In the elderly subjects with a 5-yr history of high cortisol levels and current memory deficits (n = 9), metyrapone treatment did not have any significant effect on memory performance, but hydrocortisone treatment significantly decreased delayed memory. These results suggest that memory function in elderly humans can be intensely modulated by pharmacological manipulation of glucocorticoids, although the direction of these effects depends on the cortisol history of each individual. C1 McGill Univ, Douglas Hosp, Res Ctr,Dept Psychiat, Lab Human Psychoneuroendocrine Res, Verdun, PQ H4H 1R3, Canada. Montreal Geriatr Inst, Montreal, PQ H3W 1W5, Canada. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Lupien, SJ (reprint author), McGill Univ, Douglas Hosp, Res Ctr,Dept Psychiat, Lab Human Psychoneuroendocrine Res, 6875 Lasalle Blvd, Verdun, PQ H4H 1R3, Canada. EM lupson@douglas.mcgill.ca NR 56 TC 61 Z9 65 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2002 VL 87 IS 8 BP 3798 EP 3807 DI 10.1210/jc.87.8.3798 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 581HG UT WOS:000177285400044 PM 12161513 ER PT J AU Shattuck, TM Costa, J Bernstein, M Jensen, RT Chung, DC Arnold, A AF Shattuck, TM Costa, J Bernstein, M Jensen, RT Chung, DC Arnold, A TI Mutational analysis of Smad3, a candidate tumor suppressor implicated in TGF-beta and menin pathways, in parathyroid adenomas and enteropancreatic endocrine tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-BETA; COMPARATIVE GENOMIC HYBRIDIZATION; NEOPLASIA TYPE-1 GENE; TARGETED DISRUPTION; COLORECTAL-CANCER; LOCI; CHROMOSOME-16; TUMORIGENESIS; PROLIFERATION; LOCALIZATION AB Based upon molecular allelotyping and comparative genomic hybridization studies, chromosome 15q is the likely location of a tumor suppressor gene important in the pathogeneses of sporadic enteropancreatic endocrine tumors and parathyroid adenomas. Interest has focused on Smad3 as a candidate endocrine tumor suppressor gene because 1) it is localized to 15q and 2) it encodes a TGFbeta signaling molecule that has been identified as a binding partner of the multiple endocrine neoplasm type 1 gene product menin, itself involved in enteropancreatic and parathyroid neoplasia. To determine whether Smad3 plays a primary role in development of these tumors, 20 enteropancreatic tumors and 67 parathyroid adenomas were investigated for loss of heterozygosity at DNA markers surrounding Smad3. Twenty percent of enteropancreatic tumors and 24% of parathyroid adenomas showed loss. All 9 coding exons and intron-exon boundaries of the Smad3 gene were then sequenced in genomic DNA from all 20 enteropancreatic and 25 parathyroid tumors, including every case with loss of heterozygosity. No acquired clonal mutations, insertions, or microdeletions in Smad3 were detected in any tumors. Because inactivating somatic mutation is the hallmark of an authentic tumor suppressor, Smad3 is unlikely to function as a classical tumor suppressor gene in the pathogenesis of sporadic parathyroid or enteropancreatic endocrine tumors., C1 Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA. Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT 06030 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Arnold, A (reprint author), Univ Connecticut, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. EM aarnold@nso2.uchc.edu NR 32 TC 30 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2002 VL 87 IS 8 BP 3911 EP 3914 DI 10.1210/jc.87.8.3911 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 581HG UT WOS:000177285400061 PM 12161532 ER PT J AU Park, JO Lopez, CA Gupta, VK Brown, CK Mauceri, HJ Darga, TE Manan, A Hellman, S Posner, MC Kufe, DW Weichselbaum, RR AF Park, JO Lopez, CA Gupta, VK Brown, CK Mauceri, HJ Darga, TE Manan, A Hellman, S Posner, MC Kufe, DW Weichselbaum, RR TI Transcriptional control of viral gene therapy by cisplatin SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; ISOLATED HEPATIC PERFUSION; PHASE-I; IONIZING-RADIATION; INDUCED APOPTOSIS; INTERFERON-GAMMA; CELL-DEATH; FACTOR TNF; CANCER; TOXICITY AB Ionizing radiation (IR) and radical oxygen intermediates (ROIs) activate the early growth response-1 (Egr1) promoter through specific cis-acting sequences termed CArG elements. Ad.Egr.TNF.11D, a replication-deficient adenoviral vector containing CArG elements cloned upstream of the cDNA for human recombinant TNF-alpha was used to treat human esophageal adenocarcinoma and rat colon adenocarcinoma cells in culture and as xenografts in athymic nude mice. Cisplatin, a commonly used chemotherapeutic agent, causes tumor cell death by producing DNA damage and generating ROIs. The present studies demonstrate induction of TNF-alpha production in tumor cells and xenografts treated with the combination of Ad.Egr.TNF.11D and cisplatin. The results show that the Egr1 promoter is induced by cisplatin and that this induction is mediated in part through the CArG elements. These studies also demonstrate an enhanced antitumor response without an increase in toxicity following treatment with Ad.Egr.TNF.11D and cisplatin, compared with either agent alone. Chemo-inducible cancer gene therapy thus provides a means to control transgene expression while enhancing the effectiveness of commonly used chemotherapeutic agents. C1 Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago Hosp, Ctr Adv Med, Dept Radiat & Cellular Oncol, Room 1329,Mail Code 9006,5758 S Maryland Ave, Chicago, IL 60637 USA. OI Darga, Thomas/0000-0002-8968-6701 NR 40 TC 40 Z9 47 U1 0 U2 0 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 AUG PY 2002 VL 110 IS 3 BP 403 EP 410 DI 10.1172/JCI200215548 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 581TH UT WOS:000177308900017 PM 12163460 ER PT J AU Lanone, S Zheng, T Zhu, Z Liu, W Lee, CG Ma, B Chen, QS Homer, RJ Wang, JM Rabach, LA Rabach, ME Shipley, JM Shapiro, SD Senior, RM Elias, JA AF Lanone, S Zheng, T Zhu, Z Liu, W Lee, CG Ma, B Chen, QS Homer, RJ Wang, JM Rabach, LA Rabach, ME Shipley, JM Shapiro, SD Senior, RM Elias, JA TI Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and-12 in IL-13-induced inflammation and remodeling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; ASTHMATIC AIRWAY INFLAMMATION; BRONCHOALVEOLAR LAVAGE FLUID; CHRONIC-BRONCHITIS; GELATINASE-B; ALVEOLAR MACROPHAGES; IN-VIVO; LUNG; INTERLEUKIN-13; IL-13 AB IL-13 potently stimulates eosinophilic and lymphocytic inflammation and alveolar remodeling in the lung, effects that depend on the induction of various matrix metalloproteinases (MMPs). Here, we compared the remodeling and inflammatory effects of an IL-13 transgene in lungs of wild-type, MMP-9-deficient, or MMP-12-deficient mice. IL-13-induced alveolar enlargement, lung enlargement, compliance alterations, and respiratory failure and death were markedly decreased in the absence of MMP-9 or MMP-12. Moreover, IL-13 potently induced MMPs-2, -12, -13, and -14 in the absence of MMP-9, while induction of MMPs-2, -9, -13, and -14 by IL-13 was diminished in the absence of MMP-12. A deficiency in MMP-9 did not alter eosinophil, macrophage, or lymphocyte recovery, but increased the recovery of total leukocytes and neutrophils in bronchoalveolar lavage (BAL) fluids from IL-13 transgenic mice. In contrast, a deficiency in MMP-12 decreased the recovery of leukocytes, eosinophils, and macrophages, but not lymphocytes or neutrophils. These studies demonstrate that IL-13 acts via MMPs-9 and - 12 to induce alveolar remodeling, respiratory failure, and death and that IL-13 induction of MMPs-2, -9,43, and -14 is mediated at least partially by an MMP-12-dependent pathway. The also demonstrate that MMPs-9 and -12 play different roles in the generation of IL-13-induced inflammation, with MMP-9 inhibiting neutrophil accumulation and MMP-12 contributing to the accumulation of eosinophils and macrophages. C1 Yale Univ, Sch Med, Dept Internal Med, Pulm & Crit Care Med Sect, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. Vet Adm Connecticut Healthcare Syst, Pathol & Lab Med Serv, West Haven, CT USA. Washington Univ, Barnes Jewish Hosp, Dept Med, St Louis, MO USA. Brigham & Womens Hosp, Pulm & Crit Care Med Sect, Boston, MA 02115 USA. RP Elias, JA (reprint author), Yale Univ, Sch Med, Dept Internal Med, Pulm & Crit Care Med Sect, 333 Cedar St,105 LCI,POB 208057, New Haven, CT 06520 USA. RI Lanone, Sophie/I-4042-2016 OI Lanone, Sophie/0000-0003-2509-8799 FU NHLBI NIH HHS [HL-29594, HL-47328, HL-56389, HL-61904, HL-64242, HL-70321, P01 HL029594, P01 HL056389, P50 HL056389, R01 HL047328, R01 HL064242, R01 HL070321] NR 60 TC 222 Z9 231 U1 0 U2 8 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 AUG PY 2002 VL 110 IS 4 BP 463 EP 474 DI 10.1172/JCI200214136 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 585ZL UT WOS:000177557400008 PM 12189240 ER PT J AU Songy, WB Ruoff, KL Facklam, RR Ferraro, MJ Falkow, S AF Songy, WB Ruoff, KL Facklam, RR Ferraro, MJ Falkow, S TI Identification of Streptococcus bovis biotype I strains among S-bovis clinical isolates by PCR SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SURFACE PROTEIN ANTIGEN; PHOSPHOTRANSFERASE SYSTEM; INFECTIVE ENDOCARDITIS; SALIVARY AGGLUTININ; GENE; MUTANS; CLONING; BACTEREMIA; SEQUENCE; REGION AB Streptococcus bovis causes 24% of all streptococcal infective endocarditis cases. There are many reports linking both S. bovis bacteremia and endocarditis with various forms of gastrointestinal disease (primarily colonic cancers). S. bovis is divided into two biotypes: I and II. The biotype I strain is much more frequently isolated from patients with endocarditis, gastrointestinal disease, or both. We describe here the isolation of biotype I-specific DNA sequences and the development of a PCR test which can identify S. bovis biotype I strains among S. bovis clinical isolates. C1 Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Prot Design Labs Inc, Fremont, CA 94555 USA. Massachusetts Gen Hosp, Clin Microbiol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Ctr Dis Control, Atlanta, GA 30333 USA. RP Falkow, S (reprint author), Stanford Univ, Sch Med, Dept Microbiol & Immunol, Sherman Fairchild Sci Bldg,Rm D039,299 Campus Dr, Stanford, CA 94305 USA. EM swfisher@stanford.edu NR 45 TC 10 Z9 10 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 2002 VL 40 IS 8 BP 2913 EP 2918 DI 10.1128/JCM.40.8.2913-2918.2002 PG 6 WC Microbiology SC Microbiology GA 580VA UT WOS:000177255900034 PM 12149351 ER PT J AU D'Amico, AV AF D'Amico, AV TI Predicting prostate-specific antigen recurrence established: Now, who will survive? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RADICAL RETROPUBIC PROSTATECTOMY; BEAM RADIATION-THERAPY; DEFINITIVE RADIOTHERAPY; PATHOLOGICAL STAGE; ADJUVANT THERAPY; CLINICAL UTILITY; NEURAL NETWORKS; GLEASON SCORE; CANCER; CARCINOMA C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 32 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2002 VL 20 IS 15 BP 3188 EP 3190 PG 3 WC Oncology SC Oncology GA 581HP UT WOS:000177286100003 PM 12149288 ER PT J AU Coen, JJ Zietman, AL Thakral, H Shipley, WU AF Coen, JJ Zietman, AL Thakral, H Shipley, WU TI Radical radiation for localized prostate cancer: Local persistence of disease results in a late wave of metastases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED COMPARATIVE TRIAL; DOSE-ESCALATION; THERAPY; RADIOTHERAPY; ADENOCARCINOMA; DISSEMINATION; CARCINOMA; SURVIVAL AB Purpose: To assess whether failure to maintain local control (LC) of prostate cancer after radiation therapy results in a higher incidence of distant metastasis (DM). Patients and Methods: From 1972 to 1999, 1,469 patients with clinically localized prostate cancer were treated with radical radiation therapy. Disease outcome was retrospectively reviewed for all patients with more than 2 years of follow-up. Results: The actuarial 10-year LC rate was 79%. Gleason score greater than or equal to 7, prostate-specific antigen (PSA) more than 15, and T3 to T4 tumors predicted a higher incidence of local failure (LF) (palpable recurrence or positive rebiopsy). The 10-year distant metastasis-free survival (DMFS) was 74%. Gleason score greater than or equal to 7, PSA more than 15, and T3 to T4 tumors predicted a higher incidence of distant failure. LF was the strongest predictor for DM in a multivariate model. The 10-year DMFS for LC and LF patients was 77% and 61%, respectively. Median time to distant failure was prolonged in patients with LF compared with patients with locally controlled disease (54 v 34 months). Hazard rate analysis of the time to DM revealed that patients who maintain LC have a lower rate of DM, which remains constant over time. Patients who ultimately develop LF have a higher initial rate of DM, which increases with time.. Conclusion: Patients with locally persistent prostate cancer are at greater risk of DM. The higher initial hazard of DM is consistent either with an increased likelihood of subclinical micrometastases before treatment or with posttreatment tumor embolization. The prolonged time to appearance of DM in locally failing patients and the increasing hazard of DM over time is most consistent with a late wave of metastases from a locally persistent tumor. (C) 2002 by American Society of Clinical Oncology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Coen, JJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Bloosom St,Cox 3, Boston, MA 02114 USA. NR 16 TC 141 Z9 148 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2002 VL 20 IS 15 BP 3199 EP 3205 DI 10.1200/JCO.2002.01.086 PG 7 WC Oncology SC Oncology GA 581HP UT WOS:000177286100006 PM 12149291 ER PT J AU Berlin, JD Catalano, P Thomas, JP Kugler, JW Haller, DG Benson, AB AF Berlin, JD Catalano, P Thomas, JP Kugler, JW Haller, DG Benson, AB TI Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FIRST-LINE THERAPY; CONTINUOUS-INFUSION; RANDOMIZED TRIAL; CLINICAL BENEFIT; CANCER; 5-FLUOROURACIL; LEUCOVORIN AB Purpose : Gemcitabine is generally considered to constitute first-line therapy for pancreatic cancer. To determine whether the addition of fluorouracil (5-FU) improves on the results from single-agent gemcitabine, the Eastern Cooperative Oncology Group (ECOG) compared gemcitabine plus bolus 5-FU with gemcitabine alone for patients with advanced pancreatic carcinoma. Patients and Methods: This trial involved patients with biopsy-proven, advanced carcinoma of the pancreas not amenable to surgical resection. Patients were randomized to receive either gemcitabine alone (1,000 mg/m(2)/wk) weekly for 3 weeks of every 4 or to receive gemcitabine (1,000 mg/m(2)/wk) followed by 5-FU (600 mg/m(2)/wk) weekly on the same schedule. The primary end point of the trial was survival, with secondary end points of time to progression and response rate. Results: Of 327 patients enrolled over 18 months, 322 were eligible. Overall, the median survival was 5.4 months for gemcitabine alone and 6.7 months for gemcitabine plus 5-FU (P = .09). Progression-free survival for gemcitabine alone was 2.2 months, compared with 3.4 months for gemcitabine plus 5-FU (P = .022). Objective responses were uncommon and were observed in only 5.6% of patients treated with gemcitabine and 6.9% of patients treated with gemcitabine plus 5-FU. Most toxicities were hematologic or gastrointestinal; no significant differences were noted between the two treatment arms. Conclusion: 5-FU, administered in conjunction with gemcitabine, did not improve the median survival of patients with advanced pancreatic carcinoma compared with single-agent gemcitabine. Further studies with other combinations of gemcitabine and 5-FU are not compelling, and clinical trial resources should address other combinations and novel agents. (C) 2002 by American Society of Clinical Oncology. C1 Vanderbilt Univ, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA USA. Univ Wisconsin, Madison, WI USA. Illinois Oncol Res Assoc, Peoria, IL USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Berlin, JD (reprint author), 777 Preston Res Bldg, Nashville, TN 37232 USA. FU NCI NIH HHS [CA 21076, CA 13650, CA 15488, CA 17145, CA 21115, CA 23318, CA 66636] NR 21 TC 494 Z9 516 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2002 VL 20 IS 15 BP 3270 EP 3275 DI 10.1200/JCO.2002.11.149 PG 6 WC Oncology SC Oncology GA 581HP UT WOS:000177286100016 PM 12149301 ER PT J AU Feres, M Haffajee, AD Allard, K Som, S Goodson, JM Socransky, SS AF Feres, M Haffajee, AD Allard, K Som, S Goodson, JM Socransky, SS TI Antibiotic resistance of subgingival species during and after antibiotic therapy SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE amoxicillin; antibiotics; bacteria; metronidazole; microbiology; periodontal diseases; periodontitis; resistance; subgingival plaque ID ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; RAPIDLY PROGRESSIVE PERIODONTITIS; ADULT PERIODONTITIS; REFRACTORY PERIODONTITIS; METRONIDAZOLE THERAPY; NONSURGICAL TREATMENT; ANTIMICROBIAL AGENTS; ANAEROBIC-BACTERIA; SUSCEPTIBILITY; DISEASE AB Aim: The purpose of the present investigation was to determine the percentage and identity of antibiotic-resistant species in subgingival plaque and saliva samples from chronic periodontitis patients treated by scaling and root planing followed by orally administered amoxicillin or metronidazole. Method: In all, 20 chronic periodontitis patients were selected for study. After clinical and microbiological monitoring, subjects were randomly assigned to receive either orally administered amoxicillin at the dosage of 500 mg, 3 times daily for 14 days or orally administered metronidazole at the dosage of 250 mg, 3 times daily for 14 days. For the antibiotic resistance determinations, subgingival plaque samples were taken from six posterior teeth at baseline, and 90 days; and from two randomly selected teeth at 3, 7 and 14 days during and after antibiotic administration. Samples were plated on enriched blood agar plates with or without either 2 mug/mL metronidazole or 2 mug/mL amoxicillin. Colonies were counted at 7 days. Significant differences in percentage of resistant organisms over time were determined by the Quade test. Microbial growth was washed from antibiotic-containing media and the identity of species determined using checkerboard DNA-DNA hybridization. Data were compared with those obtained in a previous study from subjects receiving SRP only or SRP followed by 14 days of orally administered doxycycline. The level of doxycycline used to determine antibiotic resistance in that study was 4 mug/mL. Results: The mean percentage of resistant isolates increased during antibiotic administration and returned to baseline levels by 90 days post therapy. The mean percentages (+/-SEM) of isolates resistant to 2 mug/mL metronidazole were 53+/-9, 65 +/- 9, 79 +/- 4 and 69 +/- 7 at baseline, 3, 7 and 14 days during antibiotic administration, and 57 +/- 4, 64 +/- 5, 62 +/- 7 and 47 +/- 6 at 3, 7, 14 and 90 days after antibiotic administration. At the same time points, the percentage of resistant isolates to amoxicillin was 0.5 +/- 0.2, 22 +/- 12, 14 +/- 5 and 37 +/- 11 during, and 31 +/- 11, 8 +/- 3, 3 +/- 2 and 3 +/- 0.6 after, administration. Antibiotic-resistant isolates of resistant species detected during or after therapy were also detected prior to therapy. The most prevalent resistant species in the metronidazole-treated group were: A. naeslundii 1, S. constellatus, A. naeslundii 2, S. mitis, S. oralis, A. odontolyticus, S. sanguis, and in the amoxicillin-treated group: S. constellatus, P. nigrescens, E. saburreum, A. naeslundii 1, S. oralis, P. melaninogenica and P. intermedia. Conclusions: Systemic antibiotic administration transiently increased the percentage of resistant subgingival species, but a major component of subgingival plaque remained sensitive to the agents during their administration. Antibiotic-resistant isolates of resistant species could be detected in samples both prior to and after therapy. However, % antibiotic-resistant isolates returned to baseline levels 90 days after antibiotic administration. C1 Guarulhos Univ, Dept Periodontol, Sao Paulo, Brazil. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Feres, M (reprint author), Guarulhos Univ, Dept Periodontol, Sao Paulo, Brazil. RI Feres, Magda/H-7964-2012 FU NIDCR NIH HHS [DE-12108, DE-11814, DE-13232, DE 12861] NR 50 TC 63 Z9 65 U1 0 U2 6 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 AUG PY 2002 VL 29 IS 8 BP 724 EP 735 DI 10.1034/j.1600-051X.2002.290809.x PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 607KQ UT WOS:000178791100009 PM 12390569 ER PT J AU Montgomery, SA Bech, P Blier, P Moller, HJ Nierenberg, AA Pinder, RM Quitkin, FM Reimitz, PE Rosenbaum, JF Rush, AJ Stassen, HH Thase, ME AF Montgomery, SA Bech, P Blier, P Moller, HJ Nierenberg, AA Pinder, RM Quitkin, FM Reimitz, PE Rosenbaum, JF Rush, AJ Stassen, HH Thase, ME TI Selecting methodologies for the evaluation of differences in time to response between antidepressants SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MAJOR DEPRESSION; PATTERN-ANALYSIS; CLINICAL-TRIALS; DOUBLE-BLIND; FLUOXETINE; PINDOLOL; ONSET; METAANALYSIS; VENLAFAXINE AB Background: The delay in the therapeutic effect of antidepressants is a considerable impediment to their successful clinical use, and attention has recently been focused on antidepressant drugs that may have a faster onset of action. Data Synthesis: Several methodologies exist for evaluating differences in time to response between antidepressants including the identification of the timepoint at which statistically or clinically significant differences between treatment groups emerge, pattern analysis, and survival analytical approaches. All have conceptual as well as practical advantages and disadvantages. Conclusion: The survival analytical approach is generally considered to be the most rigorous and sensitive in detecting differences in the speed of response of antidepressants, but the other methodologies provide useful information. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Zurich, Dept Psychiat, Zurich, Switzerland. Univ Texas, SW Med Ctr, Dallas, TX USA. NV Organon, NL-5340 BH Oss, Netherlands. Columbia Univ, Dept Psychiat, New York, NY USA. Organon Inc, W Orange, NJ USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Munich, Psychiat Clin, Munich, Germany. Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. Frederiksborg Cent Cty Hosp, Psychiat Res Unit, Hillerod, Denmark. Univ London Imperial Coll Sci Technol & Med, Sch Med, London, England. RP Montgomery, SA (reprint author), POB 8751, London W13 8WH, England. OI Rush, Augustus/0000-0003-2004-2382 NR 22 TC 34 Z9 35 U1 0 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 AUG PY 2002 VL 63 IS 8 BP 694 EP 699 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 585EC UT WOS:000177510300006 PM 12197449 ER PT J AU Foy, DW Ruzek, JI Glynn, SM Riney, SJ Gusman, FD AF Foy, DW Ruzek, JI Glynn, SM Riney, SJ Gusman, FD TI Trauma focus group therapy for combat-related PTSD: An update SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE combat-related PTSD; exposure therapy manualized treatment; group therapy; relapse prevention; cognitive restructuring; coping skills ID POSTTRAUMATIC-STRESS-DISORDER; EXPOSURE AB Individual cognitive-behavioral therapy involving directed exposure to memories of traumatic events has been found to be effective in treating post-traumatic stress disorder. In this article, we present updated information on an alternative group form of exposure therapy: manualized trauma-focus group therapy (TFGT), designed as an efficient means of conducting directed exposure, We describe the cognitive-behavioral and developmental models from which the approach was derived, present an overview of session topics and a case illustration, provide guidelines for referring individuals to TFGT, and offer suggestions for future research, (C) 2002 Wiley Periodicals, Inc. C1 Pepperdine Univ, Grad Sch Educ & Psychol, Encino, CA 91436 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Foy, DW (reprint author), Pepperdine Univ, Grad Sch Educ & Psychol, 16830 Ventura Blvd,Suite 200, Encino, CA 91436 USA. NR 12 TC 9 Z9 9 U1 1 U2 5 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 AUG PY 2002 VL 58 IS 8 BP 907 EP 918 DI 10.1002/jclp.10066 PG 12 WC Psychology, Clinical SC Psychology GA 576QX UT WOS:000177017400004 PM 12115714 ER PT J AU Fava, M Alpert, J Nierenberg, A Lagomasino, I Sonawalla, S Tedlow, J Worthington, J Baer, L Rosenbaum, JF AF Fava, M Alpert, J Nierenberg, A Lagomasino, I Sonawalla, S Tedlow, J Worthington, J Baer, L Rosenbaum, JF TI Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID TREATMENT-RESISTANT-DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; REFRACTORY DEPRESSION; MAJOR DEPRESSION; COMBINATION TREATMENT; ANTIDEPRESSANT; METAANALYSIS; CLOMIPRAMINE; FLUVOXAMINE AB In a previous study, of 41 depressed patients who had not responded to fluoxetine 20 mg/day, 53% were treated with high-dose fluoxetine (40-60 mg/day) and responded (i.e., their 17-item Hamilton Rating Scale for Depression [HAM-D-17] score was <7) versus 29% and 25% of patients treated with fluoxetine plus lithium (300-600 mg/day) or fluoxetine plus desipramine (25-50 mg/day), respectively. We wanted to assess whether these findings could be replicated in a larger sample of depressed outpatients. We identified 101 outpatients with major depressive disorder (52 men and 49 women; mean age, 41.6 + 10.6 years) who were either partial responders (n = 49) or nonresponders (n = 52) to 8 weeks of treatment with fluoxetine 20 mg/day. These patients were randomized to 4 weeks of double-blind treatment with high-dose fluoxetine (40-60 mg/day), fluoxetine plus lithium (300-600 mg/day), or fluoxetine plus desipramine (25-50 mg/day). In the overall group of patients (N = 101), there was no significant difference in response rates across the three treatment groups (high-dose fluoxetine, 42.4%; fluoxetine plus desipramine, 29.4%; fluoxetine plus lithium, 23.5%). Dropout rates were also comparable, ranging from 9.1% (high-dose fluoxetine) to 14.7% (fluoxetine plus desipramine and fluoxetine plus lithium). There were also no significant differences in response rates across the three treatment groups among partial responders (high-dose fluoxetine, 50.0%; fluoxetine plus desipramine, 33.3%; fluoxetine plus lithium, 33.3%) and nonresponders (high-dose fluoxetine, 35.3%; fluoxetine plus desiprandne, 26.3%; fluoxetine plus lithium, 12.5%). At the end of the study, the mean lithium level was 0.37 + 0.15 mEq/L (n = 27; range, 0.1-0.8 mEq/L) among lithium-treated patients, and the mean desipramine level was 104.7 + 58.8 ng/ml, (n = 22; range, 25-257 ng/mL). There were no significant relationships between lithium or desipramine blood levels and degree of improvement (as measured by the change in HAM-D-17 score). We found no significant differences in efficacy among these three treatment strategies among patients who had failed to respond adequately to 8 weeks of treatment with fluoxetine 20 mg/day, although the high-fluoxetine group was associated with nonsignificantly higher response rates in both partial responders and nonresponders. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01MH48483-05] NR 49 TC 91 Z9 96 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2002 VL 22 IS 4 BP 379 EP 387 DI 10.1097/01.jcp.0000022670.39890.6c PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 578EH UT WOS:000177104100007 PM 12172337 ER PT J AU Niaura, R Spring, B Borrelli, B Hedeker, D Goldstein, MG Keuthen, N DePue, J Kristeller, J Ockene, J Prochazka, A Chiles, JA Abrams, DB AF Niaura, R Spring, B Borrelli, B Hedeker, D Goldstein, MG Keuthen, N DePue, J Kristeller, J Ockene, J Prochazka, A Chiles, JA Abrams, DB TI Multicenter trial of fluoxetine as an adjunct to behavioral smoking cessation treatment SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED-TRIAL; WITHDRAWAL SYMPTOMS; CIGARETTE-SMOKING; MAJOR DEPRESSION; BULIMIA-NERVOSA; RATING-SCALE; MISSING DATA; DOUBLE-BLIND; WEIGHT-GAIN AB The authors evaluated the efficacy of fluoxetine hydrochloride (Prozac; Eli Lilly and Company, Indianapolis, IN) as an adjunct to behavioral treatment for smoking cessation. Sixteen sites randomized 989 smokers to 3 dose conditions: 10 weeks of placebo, 30 mg, or 60 mg fluoxetine per day. Smokers received 9 sessions of individualized cognitive-behavioral therapy, and biologically verified 7-day self-reported abstinence follow-ups were conducted at 1, 3, and 6 months posttreatment. Analyses assuming missing data counted as smoking observed no treatment difference in outcomes. Pattern-mixture analysis that estimates treatment effects in the presence of missing data observed enhanced quit rates associated with both the 60-mg and 30-mg doses. Results support a modest, short-term effect of fluoxetine on smoking cessation and consideration of alternative models for handling missing data. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Univ Illinois, Prevent Res Ctr, Chicago, IL 60680 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Indiana State Univ, Dept Psychol, Terre Haute, IN 47809 USA. Vet Affairs Med Ctr, Denver, CO USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. RP Niaura, R (reprint author), Miriam Hosp, Ctr Behav Med, Coro Bldg,Suite 500,1 Hoppin St, Providence, RI 02903 USA. EM raymond_niaura@brown.edu OI Borrelli, Belinda/0000-0002-0859-796X FU NCI NIH HHS [P50 CA084719, CA84719]; NHLBI NIH HHS [HL32318, R01 HL032318] NR 50 TC 58 Z9 59 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2002 VL 70 IS 4 BP 887 EP 896 DI 10.1037//0022-006X.70.4.887 PG 10 WC Psychology, Clinical SC Psychology GA 582JP UT WOS:000177347400003 PM 12182272 ER PT J AU Chuang, SK Wei, LJ Douglass, CW Dodson, TB AF Chuang, SK Wei, LJ Douglass, CW Dodson, TB TI Risk factors for dental implant failure: A strategy for the analysis of clustered failure-time observations SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE survival analysis; dental implants; risk factors; follow-up study; correlation and dependence; Cox regression analysis; clustered survival data; marginal approach ID PARTIALLY EDENTULOUS JAWS; PROSPECTIVE MULTICENTER; ENDOSSEOUS IMPLANTS; REGRESSION-ANALYSIS; ITI-IMPLANTS; COMPLICATIONS; SURVIVAL; SUCCESS; MODELS AB This study's objective was to identify, in a statistically valid and efficient manner, the risk factors associated with dental implant failure. We hypothesize that factors exist which can be modified by clinicians to enhance outcome. A retrospective cohort study design was used. Cohort members had greater than or equal to one implant placed. Risk factors were classified as demographic, health status, implant-, anatomic-, or prosthetic-specific, and reconstructive variables. The outcome variable was implant failure. The cohort was composed of 677 patients who had 2349 implants placed. Based on the adjusted multivariate model, factors associated with implant failure were tobacco use, implant length, staging, well size, and immediate implants (p less than or equal to 0.05). In the setting of correlated survival observations, we recommend adjusting for the correlation of the observations to provide statistically valid and efficient results. Three of the identified factors-tobacco use, immediate implants, and implant staging-potentially may be modified to enhance implant survival. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. RP Chuang, SK (reprint author), Chestnut Hill Stn, POB 67376, Chestnut Hill, MA 02467 USA. EM schuang@hsph.harvard.edu FU NCI NIH HHS [R01 CA56844]; NIDCR NIH HHS [K24 DE000448, K16 DE000275] NR 30 TC 117 Z9 120 U1 0 U2 8 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 AUG PY 2002 VL 81 IS 8 BP 572 EP 577 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 579WL UT WOS:000177201300016 PM 12147750 ER PT J AU Bair, AE Filbin, MR Kulkarni, RG Walls, RM AF Bair, AE Filbin, MR Kulkarni, RG Walls, RM TI The failed intubation attempt in the Emergency Department: Analysis of prevalence, rescue techniques, and personnel SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE airway; intubation; rescue airway management; rapid sequence intubation; RSI; NEAR ID RAPID-SEQUENCE INTUBATION; LARYNGEAL MASK AIRWAY; DIFFICULT AIRWAY; FIBEROPTIC INTUBATION; MANAGEMENT; CRICOTHYROTOMY; PATIENT AB The aims of this study were: To describe the prevalence of Emergency Department (ED) airway management failures requiring rescue maneuvers, to describe successful rescue methods used when the primary method chosen is unsuccessful, and to characterize the roles of emergency physicians and other specialists in rescue airway management. A prospective observational study was conducted of ED airway management in 30 hospitals in the USA, Canada, and Singapore participating in the National Emergency Airway Registry (NEAR) database project. Patients were entered in the study if they underwent ED airway management, the first method chosen was not successful in achieving intubation, and a rescue technique was required. Data were collected on a structured data form for entry into a relational database with subsequent search for subjects fulfilling inclusion and exclusion criteria. Descriptive statistics were used for analysis of these data. There were 7,712 patients identified who underwent emergency intubation during the study period from January 1998 to February 2001. A total of 207 (2.7%) patient intubations met the inclusion criteria. Of these, 102 (49%) patients underwent rescue rapid sequence intubation (RSI). RSI was used after failure of oral intubation with sedation alone (n = 29), oral intubation without medications (n = 37), or blind nasotracheal intubation (n 36). Forty-three (21%) patients underwent rescue cricothyrotomy after failure of RSI (n = 26) or other intubation methods (n = 17). Seventy-nine percent of rescue RSIs and 53% of rescue surgical airways were performed by emergency physicians. In conclusion, a total of 2.7% of emergency intubations required rescue. RSI is the most commonly used first line technique for ED airway management and is also the principal back-up technique when other oral or nasal intubation methods fail. Emergency physicians manage the majority of ED intubations, including those requiring rescue techniques. (C) 2002 Elsevier Science Inc. C1 Univ Calif Davis, Med Ctr, Div Emergency Med, Dept Internal Med, Sacramento, CA 95817 USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Train, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Emergency Med,Div Emergency, Boston, MA 02115 USA. RP Bair, AE (reprint author), Univ Calif Davis, Med Ctr, Div Emergency Med, Dept Internal Med, 2315 Stockton Blvd,PSSB 2100, Sacramento, CA 95817 USA. NR 26 TC 75 Z9 78 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2002 VL 23 IS 2 BP 131 EP 140 AR PII S0736-4679(02)00501-2 DI 10.1016/S0736-4679(02)00501-2 PG 10 WC Emergency Medicine SC Emergency Medicine GA 599ZN UT WOS:000178365700004 PM 12359280 ER PT J AU Evans, AJ Nadel, ES Brown, DFM Biddinger, P Peters, J Finkel, M Bontempo, L Peak, D Nagurney, T AF Evans, AJ Nadel, ES Brown, DFM Biddinger, P Peters, J Finkel, M Bontempo, L Peak, D Nagurney, T TI Altered mental status and agitation SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID SUPPURATIVE OTITIS-MEDIA; BACTERIAL-MENINGITIS; UNITED-STATES; INTRACRANIAL COMPLICATIONS; STREPTOCOCCUS-PNEUMONIAE; ACUTE MASTOIDITIS; ECHOCARDIOGRAPHY; ENDOCARDITIS; ANTIBIOTICS; DIAGNOSIS C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Div Emergency Med, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2002 VL 23 IS 2 BP 199 EP 202 AR PII S0736-4679(02)00507-3 DI 10.1016/S0736-4679(02)00507-3 PG 4 WC Emergency Medicine SC Emergency Medicine GA 599ZN UT WOS:000178365700015 PM 12359291 ER PT J AU Shirakami, A Toyonaga, T Tsuruzoe, K Shirotani, T Matsumoto, K Yoshizato, K Kawashima, J Hirashima, Y Miyamura, N Kahn, CR Araki, E AF Shirakami, A Toyonaga, T Tsuruzoe, K Shirotani, T Matsumoto, K Yoshizato, K Kawashima, J Hirashima, Y Miyamura, N Kahn, CR Araki, E TI Heterozygous knockout of the IRS-1 gene in mice enhances obesity-linked insulin resistance: a possible model for the development of type 2 diabetes SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; PROTEIN-KINASE-C; BETA-CELL GROWTH; RECEPTOR SUBSTRATE-1; GLUCOSE-TRANSPORT; SKELETAL-MUSCLE; FACTOR-I; MELLITUS; NIDDM; LIVER AB Insulin receptor substrate 1 (IRS-1) gene polymorphisms have been identified in type 2 diabetic patients; however, it is unclear how such polymorphisms contribute to the development of diabetes. Here we introduced obesity in heterozygous IRS-1 knockout (IRS-1(+/-)) mice by gold-thioglucose (GTG) injection and studied the impact of reduced IRS-1 expression on obesity-linked insulin resistance. GTG injection resulted in similar to30% weight gain in IRS-1(+/-) and wild type (WT) mice, compared with saline-injected controls. There was no difference in insulin sensitivity between lean IRS-1(+/-) and lean WT. Elevated fasting insulin levels but no change in fasting glucose were noted in obese IRS-1(+/-) and WT compared with the respective lean controls. Importantly, fasting insulin in obese IRS-1(+/-) was 1.5-fold higher (P<0.05) than in obese WT, and an insulin tolerance test showed a profound insulin resistance in obese IRS-1(+/-) compared with obese WT. The islets of obese IRS-1(+/-) were 1.4-fold larger than those of obese WT. The expression of insulin receptor and IRS-1 and IRS-2 was decreased in obese IRS-1(+/-), which could in part explain the profound insulin resistance in these mice. Our results suggest that IRS-1 is the suspected gene for type 2 diabetes and its polymorphisms could worsen insulin resistance in the presence of other additional factors, such as obesity. C1 Kumamoto Univ, Dept Metab Med, Sch Med, Kumamoto 8608556, Japan. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Araki, E (reprint author), Kumamoto Univ, Dept Metab Med, Sch Med, 1-1-1 Honjo, Kumamoto 8608556, Japan. NR 44 TC 32 Z9 34 U1 0 U2 3 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD AUG PY 2002 VL 174 IS 2 AR UNSP 0022-0795/02/0174-309 DI 10.1677/joe.0.1740309 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 587CV UT WOS:000177623700017 PM 12176670 ER PT J AU Gill-Leertouwer, TC Gussenhoven, EJ Bosch, JL Deinum, J van Overhagen, H Derkx, FHM Pattynama, PMT AF Gill-Leertouwer, TC Gussenhoven, EJ Bosch, JL Deinum, J van Overhagen, H Derkx, FHM Pattynama, PMT TI Predictors for clinical success at one year following renal artery stent placement SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE renal artery stenosis; atherosclerosis; stents; hypertension; intravascular ultrasound ID BALLOON ANGIOPLASTY; INTRAVASCULAR ULTRASOUND; RENIN SECRETION; STENOSIS; HYPERTENSION; CAPTOPRIL; FLOW AB Purpose: To determine pretreatment variables that may predict 1-year clinical outcome of stent placement for renal artery stenosis. Methods: In a prospective study, 40 consecutive patients (29 men; mean age 60 +/- 9.1 years) with angiographically proven atherosclerotic renal artery stenosis were treated with stent placement because of drug resistant hypertension (n=14), renal function impairment (n=14), or both (n=12). Clinical success at 1 year was defined as a decrease of diastolic blood pressure greater than or equal to10 mmHg or a decrease in serum creatinine greater than or equal to20%, depending on the indication for treatment. Regression analysis was performed using anatomical parameters from angiography and intravascular ultrasound, estimates of renal blood flow from renal scintigraphy, and single-kidney renal function measurements. Results: Patients treated for hypertension had better outcome than those treated for renal function impairment, with clinical success rates of 85% and 35%, respectively. Preserved renal function, with low serum creatinine and high 2-kidney glomerular filtration rate at baseline, was associated with clinical success in the entire patient group at follow-up (p=0.02 and p=0.03, respectively). An elevated vein-to-artery renin ratio on the affected side was borderline predictive (p=0.06). In patients treated for renal impairment, lateralization to the affected kidney (affected kidney-to-2-kidney count ratio less than or equal to0.45) on the scintigram emerged as a significant predictor for clinical success, with an odds ratio of 15 (p=0.048). Conclusions: Clinical success of renal artery stent placement is better for the treatment of hypertension than for preserving renal function. In patients with renal function impairment, lateralization to the affected kidney on the scintigram appears to be a predictor of clinical success. C1 Erasmus Univ, Ctr Med, Dept Radiol, NL-3015 GD Rotterdam, Netherlands. Erasmus Univ, Ctr Med, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands. Erasmus Univ, Ctr Med, Dept Cardiol, NL-3015 GD Rotterdam, Netherlands. Interuniv Cardiol Inst Netherlands, Rotterdam, Netherlands. Ziekenhis Leyenburg, Dept Radiol, The Hague, Netherlands. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pattynama, PMT (reprint author), Erasmus Univ, Ctr Med, Dept Radiol, Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands. RI Deinum, Jacob/D-3613-2009 NR 19 TC 15 Z9 17 U1 0 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD AUG PY 2002 VL 9 IS 4 BP 495 EP 502 DI 10.1583/1545-1550(2002)009<0495:PFCSAO>2.0.CO;2 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 599CW UT WOS:000178317400019 PM 12223011 ER PT J AU Casarett, D Karlawish, J Asch, DA AF Casarett, D Karlawish, J Asch, DA TI Paying hypertension research subjects - Fair compensation or undue inducement? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE research ethics; informed consent; inducement; hypertension AB CONTEXT: Cash payments are often used to compensate subjects who participate in research. However, ethicists have argued that these payments might constitute an undue inducement. OBJECTIVES: To determine whether potential subjects agree with theoretical arguments that a payment could be an undue inducement. DESIGN/SETTING/PARTICIPANTS: Survey of 350 prospective jurors. MAIN OUTCOME MEASURES: Belief that a $500 payment for research participation would Impair their own, and others' ability to think carefully about the risks and benefits of a clinical trial. RESULTS: Two hundred sixty-one jurors (74.6%) believed that a $500 payment would impair subjects' ability to think carefully about the risks and benefits of research. Ninety-six of 120 (80%) expressed this concern about subjects with a low Income (<$20,000) compared to 92/117 (79%) of those with a middle income ($20,000 to $50,000). and 73/113 (65%) with a high Income (>$50,000). In contrast, only 69 (19.7%) of jurors believed that a $500 payment would influence them. Jurors who believed that this payment would Influence them reported lower Incomes and less education. CONCLUSION: Members of the general public share ethical concerns about the Influence of payments for research, although they believe that these concerns are more applicable to others than to themselves. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Ctr Bioeth, Dept Med, Div Geriatr,Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Casarett, D (reprint author), Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 4 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2002 VL 17 IS 8 BP 650 EP 652 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 587YX UT WOS:000177672900011 PM 12213148 ER PT J AU Stone, RM AF Stone, RM TI New therapies in leukemia: Renewed hope SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; SOUTHWEST-ONCOLOGY-GROUP; ARSENIC TRIOXIDE; RESISTANCE; MUTATIONS; CYTARABINE; INHIBITOR; EFFICACY; CANCER C1 Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Adult Leukemia Program, 44 Binney St,D840, Boston, MA 02115 USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. Hematother. Stem Cell Res. PD AUG PY 2002 VL 11 IS 4 BP 583 EP 587 DI 10.1089/15258160260194730 PG 5 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 583ED UT WOS:000177392900003 PM 12201947 ER PT J AU Zhao, DXM Hu, YY Miller, GG Luster, AD Mitchell, RN Libby, P AF Zhao, DXM Hu, YY Miller, GG Luster, AD Mitchell, RN Libby, P TI Differential expression of the IFN-gamma-inducible CXCR3-binding chemokines, IFN-inducible protein 10, monokine induced by IFN, and IFN-inducible T cell alpha chemoattractant in human cardiac allografts: Association with cardiac allograft vasculopathy and acute rejection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; INTERFERON-GAMMA; CXC CHEMOKINES; CORONARY ARTERIOSCLEROSIS; RECEPTOR CXCR3; IP-10; TRANSPLANTATION; ANGIOGENESIS; LEUKOCYTES; DISEASE AB CXCR3 chemokines exert potent biological effects on both immune and vascular cells. The dual targets suggest their important roles in cardiac allograft vasculopathy (CAV) and rejection. Therefore, we investigated expression of IFN-inducible protein 10 (IP-10), IFN-inducible T cell a chemoattractant (1-TAC), monokine induced by IFN (Mig), and their receptor CXCR3 in consecutive endomyocardial biopsies (n = 133) from human cardiac allografts and corresponding normal donor hearts (n = 11) before transplantation. Allografts, but not normal hearts, contained IP-10, Mig, and I-TAC mRNA. Persistent elevation of IP-10 and I-TAC was associated with CAV. Allografts with CAV had an IP-10-GAPDH ratio 3.7 +/- 0.8 compared with 0.8 +/- 0.2 in those without CAV (p = 0.004). Similarly, I-TAC mRNA levels were persistently elevated in allografts with CAV (6.7 +/- 1.9 in allografts with vs 1.5 +/- 0.3 in those without CAV, p = 0.01). In contrast, Mig mRNA was induced only during rejection (2.4 +/- 0.9 with vs 0.6 +/- 0.2 without rejection, p = 0.015). In addition, IP-10 mRNA increased above baseline during rejection (4.1 +/- 2.3 in rejecting vs 1.8 +/- 1.2 in nonrejecting biopsies, p = 0.038). I-TAC did not defer significantly with rejection. CXCR3 mRNA persistently elevated after cardiac transplantation. Double immunohistochemistry revealed differential cellular distribution of CXCR3 chemokines. Intragraft vascular cells expressed high levels of IP-10 and I-TAC, while Mig localized predominantly in infiltrating macrophages. CXCR3 was localized in vascular and infiltrating cells. CXCR3 chemokines are induced in cardiac allografts and differentially associated with CAV and rejection. Differential cellular distribution of these chemokines in allografts indicates their central roles in multiple pathways involving CAV and rejection. This chemokine pathway may serve as a monitor and target for novel therapies to prevent CAV and rejection. C1 Vanderbilt Univ, Med Ctr, Dept Cardiac Surg, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Cardiovasc Med, Boston, MA 02115 USA. RP Zhao, DXM (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, 2311 Pierce Ave,PCHI Room 2229, Nashville, TN 37232 USA. FU NCI NIH HHS [CA69212]; NHLBI NIH HHS [HL53771, HL 43364, T32HL07604] NR 27 TC 143 Z9 155 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2002 VL 169 IS 3 BP 1556 EP 1560 PG 5 WC Immunology SC Immunology GA 576UV UT WOS:000177025100052 PM 12133984 ER PT J AU Caselli, A Bedi, DS O'Connor, C Shah, C Veves, A AF Caselli, A Bedi, DS O'Connor, C Shah, C Veves, A TI Assessment of laser Doppler perfusion imager's in vivo reliability: Can it be used for a prospective analysis? SO JOURNAL OF LASER APPLICATIONS LA English DT Article DE laser Doppler; biological zero; microcirculation; endothelial function ID SKIN BLOOD-FLOW; BIOLOGICAL ZERO; ENDOTHELIAL FUNCTION; SODIUM-NITROPRUSSIDE; FOREARM SKIN; MICROCIRCULATION; REACTIVITY; MACROCIRCULATION; ACETYLCHOLINE; VASODILATION AB The aim of this study was to assess the reliability of the laser Doppler perfusion imager (Lisca PIM 1.0; Lisca development, Linkoping, Sweden) for longitudinal analysis. We measured the skin blood flow under a biological zero condition at the forearm level in 84 patients enrolled in a 12 week prospective interventional trial. Since the biological zero is the background reading registered by the laser when blood flow has been occluded, any fluctuation of the measurements obtained under this condition can be attributable to the laser scanner's variability rather than biological variation. After the blood flow of the arm was occluded and arrested by a pressure cuff, blood perfusion readings were taken before and after the iontophoresis of a 1% acetylcholine chloride solution and a 1% sodium nitroprusside solution at the beginning of the study and during the two follow-up visits. A total of 927 biological zero readings were recorded throughout the study. The coefficient of variation of these measurements was 15.7% +/- 8.5%. We conclude that laser Doppler perfusion imaging is a reliable and reproducible technique to assess the skin blood flow for prospective study since the variability of the measurements depending on the instrument itself is low. (C) 2002 Laser Institute of America. C1 Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. Univ Roma Tor Vergata, Dept Internal Med, I-00173 Rome, Italy. RP Veves, A (reprint author), Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Dept Surg, Boston, MA 02215 USA. NR 21 TC 4 Z9 4 U1 1 U2 1 PU LASER INST AMER PI ORLANDO PA 13501 INGENUITY DR, SUITE 128, ORLANDO, FL 32826 USA SN 1042-346X J9 J LASER APPL JI J. Laser Appl. PD AUG PY 2002 VL 14 IS 3 BP 198 EP 202 DI 10.2351/1.1494084 PG 5 WC Materials Science, Multidisciplinary; Optics; Physics, Applied SC Materials Science; Optics; Physics GA 585TJ UT WOS:000177540400010 ER PT J AU Blanton, SH Liang, CY Cai, MW Pandya, A Du, LL Landa, B Mummalanni, S Li, KS Chen, ZY Qin, XN Liu, YF Balkany, T Nance, WE Liu, XZ AF Blanton, SH Liang, CY Cai, MW Pandya, A Du, LL Landa, B Mummalanni, S Li, KS Chen, ZY Qin, XN Liu, YF Balkany, T Nance, WE Liu, XZ TI A novel locus for autosomal dominant non-syndromic deafness (DFNA41) maps to chromosome 12q24-qter SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID LINKAGE ANALYSIS; GENE AB We have studied 36 subjects in a large multigenerational Chinese family that, is segregating for an autosomal dominant adult onset form of progressive non-syndromic hearing loss. All affected subjects had bilateral sensorineural hearing loss involving all frequencies with some significant gender differences in initial presentation. After excluding linkage to known loci for non-syndromic deafness, we used the Center for Inherited Disease Research (CIDR) to test for 351 polymorphic markers distributed at approximately 10 cM intervals throughout the genome. Analysis of the resulting data provided evidence that the locus designated DFNA41 maps to a 15 cM region on chromosome 12q24.32-qter, proximal to the marker D12S1609. A maximum two point lod score of 6.56 at theta=0.0 was obtained for D12S343. This gene is distal to DFNA25, a previously identified locus for dominant adult onset hearing loss that maps to 12q21-24. Positional/functional candidate genes in this region include frizzled 10, epimorphin, RAN, and ZFOC1. C1 Univ Miami, Dept Otolaryngol D48, Miami, FL 33136 USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23284 USA. W China Univ Med Sci, Dept Otolaryngol, Chengdu 610041, Peoples R China. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Dept Neurobiol, Sch Med, Boston, MA 02115 USA. Univ Virginia, Dept Pediat, Charlottesville, VA 22903 USA. RP Liu, XZ (reprint author), Univ Miami, Dept Otolaryngol D48, 1666 NW 12th Ave, Miami, FL 33136 USA. FU NIDCD NIH HHS [DC 004293, DC 05575] NR 13 TC 18 Z9 20 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2002 VL 39 IS 8 BP 567 EP 570 DI 10.1136/jmg.39.8.567 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 584GK UT WOS:000177458700005 PM 12161595 ER PT J AU Greco, JB Sakaie, KE Aminipour, S Lee, PL Chang, LL He, J Westmoreland, S Lackner, AA Gonzalez, RG AF Greco, JB Sakaie, KE Aminipour, S Lee, PL Chang, LL He, J Westmoreland, S Lackner, AA Gonzalez, RG TI Magnetic resonance spectroscopy: an in vivo tool for monitoring cerebral injury in SIV-infected macaques SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Symposium on Nonhuman Primate Models for AIDS CY NOV 07-10, 2001 CL SAN JUAN, PUERTO RICO SP BD Biosci Pharmingen, Glaxo, Res Ctr Minor Inst Program, Univ Puerto Rico, Med Sci Campus, Off Chancellor, Unit Comparat Med, Virol Lab, Dept Microl DE choline; juvenile; N-acetyl-aspartate ID SIMIAN IMMUNODEFICIENCY VIRUS; AIDS DEMENTIA COMPLEX; PROTON MR SPECTROSCOPY; HIV-SEROPOSITIVE INDIVIDUALS; COGNITIVE MOTOR COMPLEX; METABOLITE ABNORMALITIES; NEURONAL INJURY; ANTIRETROVIRAL THERAPY; N-ACETYLASPARTATE; POSITIVE PATIENTS AB The purpose of our study was to demonstrate the feasibility of using in vivo proton Magnetic Resonance Spectroscopy (MRS) to monitor the brain manifestations of SIV infection in the macaque model of AIDS. Previous spectroscopy work on macaque brain tissue and in vivo work in humans is reviewed to provide the motivation and context for this study. We collected 34 MRS data sets on 14 uninfected rhesus macaques. From this data, we demonstrate that we are capable of detecting changes similar to those observed in human MRS studies for most metabolites using less than 10 animals. The juvenile macaques utilized in this study demonstrate age-related changes in the levels of N-acetyl aspartate (NAA), a neuronal marker. The quantity and distribution of neurocheMicals in the macaque are found to be slightly, but significantly, different than in the human. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Dept Neuroradiol, Charlestown, MA USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Gonzalez, RG (reprint author), Gray 2 Room B 285,55 Fruit St, Boston, MA 02114 USA. OI SAKAIE, KEN/0000-0002-5633-4494 FU NCRR NIH HHS [R01-RR13213, P51RR00168-39]; NINDS NIH HHS [R01-NS34626] NR 59 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2002 VL 31 IS 4-5 BP 228 EP 236 DI 10.1034/j.1600-0684.2002.02009.x PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 594AT UT WOS:000178027200010 PM 12390545 ER PT J AU Small, GW AF Small, GW TI Brain-imaging surrogate markers for detection and prevention of age-related memory loss SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Alzheimer's disease; apolipoprotein E; positron emission tomography; cerebral glucose metabolism; functional magnetic resonance imaging; genetic risk ID CEREBRAL BLOOD-FLOW; E TYPE-4 ALLELE; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; SENSORY STIMULATION; RISK; ACTIVATION; METABOLISM; SIZE AB Recent evidence points to the importance of neuropathological and cognitive changes preceding Alzheimer's disease (AD), and clinical trials have begun to focus on preventive treatments designed to slow age-related cognitive decline and delay the onset of AD in people with age-associated memory impairment (AAMI). Studying subjects with few deficits leads to diagnostic heterogeneity and a need for larger samples in order to detect active drug effects. In this report, I review results of recent studies designed to address such issues. Middle-aged and older adults with mild memory complaints were studied using brain imaging and measures of the major known genetic risk for AD, the apolipoprotein E-4 (APOE-4) allele. In a study of positron emission tomography during mental rest, glucose metabolic rates were significantly lower in APOE-4 carriers in brain regions affected by AD. Another study using functional magnetic resonance imaging showed increased brain activation during memory tasks in APOE-4 carriers in similar brain regions. Longitudinal follow-up after 2 yr indicated the potential utility of such brain-imaging measures, combined with genetic-risk information, as surrogate markers in treatment trials for AAMI to prevent further cognitive decline. Current development focuses on novel technologies using positron emission tomography to directly image the neuritic plaques and neurofibrillary tangles of AD in order to provide more specific measures of disease progression in future clinical trials. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, 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, Inst Neuropsychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIA NIH HHS [AG10123, AG13308]; NIMH NIH HHS [MH52453] NR 28 TC 10 Z9 11 U1 3 U2 7 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 AUG-OCT PY 2002 VL 19 IS 1-2 BP 17 EP 21 DI 10.1007/s12031-002-0005-7 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 590AJ UT WOS:000177794700004 PM 12212776 ER PT J AU Goto, JJ Tanzi, RE AF Goto, JJ Tanzi, RE TI The role of the low-density lipoprotein receptor-related protein (LRP1) in Alzheimer's A beta generation SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE low-density lipoprotein receptor-related protein (LRP1); receptor-associated protein (RAP); A beta clearance ID AMYLOID PRECURSOR PROTEIN; DISEASE AB The clearance and degradation of extracellular Abeta is critical for regulating beta-amyloid deposition, a major hallmark of brains of patients with Abeta in Alzheimer's Disease. The low-density lipoprotein receptor-related protein, LRP1, is a large endocytic receptor that significantly contributes to the balance between degradation and production of Abeta. An extracellular portion of the LRP, known as the cluster II region can bind to the secreted form of APP (sAPP-KPI). We show here that a GST fusion protein containing the cluster II region of LRP can be used as a 'mini-receptor' that specifically binds to sAPP-KPI from conditioned cultured medium. The binding between the GST-LRP-cluster II fusion protein and sAPP-KPI can be inhibited with the strong binding ligand of LRP1, called receptor-associated protein (RAP). Furthermore, a cell-based in vitro assay system has been developed to monitor the production of total Abeta and Abeta(1-42) in the presence and absence of RAP in Chinese hamster ovary (CHO) cell lines both deficient in LRP and expressing LRP. A 3-day treatment of the L2 (CHO cells deficient in LRP and overexpressing APP751) and L3 (CHO cells expressing LRP and overexpressing APP751) cell lines with RAP showed a decrease in total AD and, interestingly, also a decrease in the ratio of Abeta(42)/Abeta(total) This cell-based model system and LRP-cluster II mini-receptor will be very useful for screening novel compounds that can reduce Abeta accumulation by inhibiting binding of APP-KPI to LRP1. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Aging Genet & Neurodengenerat, Dept Neurol,Genet & Aging Res Unit, Boston, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Aging Genet & Neurodengenerat, Dept Neurol,Genet & Aging Res Unit, 114 16th St, Boston, MA 02129 USA. NR 5 TC 20 Z9 20 U1 0 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 AUG-OCT PY 2002 VL 19 IS 1-2 BP 37 EP 41 DI 10.1007/s12031-002-0008-4 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 590AJ UT WOS:000177794700007 PM 12212791 ER PT J AU Rogers, JT Randall, JD Eder, PS Huang, XD Bush, AI Tanzi, RE Venti, A Payton, SM Giordano, T Nagano, S Cahill, CM Moir, R Lahiri, DK Greig, N Sarang, SS Gullans, SR AF Rogers, JT Randall, JD Eder, PS Huang, XD Bush, AI Tanzi, RE Venti, A Payton, SM Giordano, T Nagano, S Cahill, CM Moir, R Lahiri, DK Greig, N Sarang, SS Gullans, SR TI Alzheimer's disease drug discovery targeted to the APP mRNA 5 ' untranslated region SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Alzheimer's disease; APP mRNA 5 ' untranslated region; RNA-targeting; FDA-2000 Drug library; drug screen; translation ID AMYLOID PRECURSOR PROTEIN; MESSENGER-RNA; INTERLEUKIN-1; TRANSLATION; SEQUENCES; GENES; MODEL AB We performed a screen for drugs that specifically interact with the 5' untranslated region of the mRNA coding for the Alzheimer's Amyloid Precursor Protein (APP). Using a transfection based assay, in which APP 5'UTR sequences drive the translation of a downstream luciferase reporter gene, we have been screening for new therapeutic compounds that already have FDA approval and are pharmacologically and clinically well-characterized. Several classes of FDA-pre-approved drugs (16 hits) reduced APP 5'UTR-directed luciferase expression (> 95% inhibition of translation). The classes of drugs include known blockers of receptor ligand interactions, bacterial antibiotics, drugs involed in lipid metabolism, and metal chelators. These APP 5'UTR directed drugs exemplify a new strategy to identify RNA-directed agents to lower APP translation and Abeta peptide output for Alzheimer's disease therapeutics. C1 Harvard Univ, Massachusetts Gen Hosp E, Sch Med,Ctr Neurosci, Dept Psychiat Neurosci,Genet & Aging Unit, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02115 USA. Message Pharmaceut, Malvern, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Res Unit, Boston, MA USA. Indiana Univ, Sch Med, Inst Psychiat Res, Indianapolis, IN 46202 USA. RP Rogers, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp E, Sch Med,Ctr Neurosci, Dept Psychiat Neurosci,Genet & Aging Unit, Bldg 114,16th St,3850, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIMH NIH HHS [5KO1 MH02001-02] NR 16 TC 38 Z9 39 U1 0 U2 1 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 AUG-OCT PY 2002 VL 19 IS 1-2 BP 77 EP 82 DI 10.1007/s12031-002-0014-6 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 590AJ UT WOS:000177794700013 PM 12212798 ER PT J AU Guenette, SY Chang, Y Hyman, BT Tanzi, RE Rebeck, GW AF Guenette, SY Chang, Y Hyman, BT Tanzi, RE Rebeck, GW TI Low-density lipoprotein receptor-related protein levels and endocytic function are reduced by overexpression of the FE65 adaptor protein, FE65L1 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amyloid precursor protein; degradation; FE65; FE65L1; low density lipoprotein receptor-related protein (LRP); secreted LRP ID AMYLOID PRECURSOR PROTEIN; PHOSPHOTYROSINE-BINDING DOMAIN; CYTOPLASMIC DOMAIN; ALZHEIMERS-DISEASE; ALPHA-2-MACROGLOBULIN RECEPTOR; INTRACELLULAR DOMAIN; APOLIPOPROTEIN-E; BETA-PROTEIN; LRP; SECRETION AB The FE65 adaptor protein family was identified in two-hybrid screens as proteins that bind the cytoplasmic domain of the amyloid precursor protein (APP). Studies have shown that FE65 binding to APP modulates APP processing. Increased levels of alpha-secretase derived secreted APP (APPsalpha) and beta-amyloid (Abeta) were recovered from conditioned media upon FE65L1 or FE65 overexpression. These effects were associated with an increase in the ratio of mature/immature APP and increased cell-surface APP. FE65 has also been reported to bind low-density lipoprotein receptor-related protein (LRP). Here we show that FE65L1 overexpression results in decreased LRP steady state levels, LRPs, and LRP endocytic receptor function. These changes in LRP protein levels are not due to decreased transcription of LRP. Furthermore, pulse/chase experiments demonstrate that changes in LRP protein only occurred 12-18 h after translation. We conclude that the decreases in LRP levels likely reflect routing of LRP away from the cell surface into a degradative pathway. Previous studies suggested that LRP plays an important role for Abeta production of Kunitz protease inhibitor forms of APP in the endocytic pathway. These data show that FE65L1 can differentially affect the metabolic fate of APP and LRP. In addition, these data suggest that the LRP decrease observed in FE65L1 overexpressing cells may in part contribute to altered APP processing. C1 Harvard Univ, Massachusetts Gen Hosp,Dept Neurol, Genet & Aging Res Unit, Ctr Aging Genet & Neurodegenerat,Sch Med, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp,Dept Neurol, Alzheimers Res Unit, Ctr Aging Genet & Neurodegenerat,Sch Med, Charlestown, MA USA. RP Guenette, SY (reprint author), Massachusetts Gen Hosp E, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG15903, AG12406] NR 52 TC 21 Z9 22 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2002 VL 82 IS 4 BP 755 EP 762 DI 10.1046/j.1471-4159.2002.01009.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 582UJ UT WOS:000177369300003 PM 12358780 ER PT J AU Kinoshita, A Whelan, CM Smith, CJ Berezovska, O Hyman, BT AF Kinoshita, A Whelan, CM Smith, CJ Berezovska, O Hyman, BT TI Direct visualization of the gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein: association with Fe65 and translocation to the nucleus SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE adapter protein; amyloid precursor protein; Fe65; FRET; gamma cleavage; intracellular domain ID PHOSPHOTYROSINE-BINDING DOMAIN; RESONANCE ENERGY-TRANSFER; INTRACELLULAR DOMAIN; CYTOPLASMIC DOMAIN; NOTCH; PRESENILIN; PROTEOLYSIS; MUTATIONS; CLEAVAGE; DISEASE AB Amyloid-beta, the peptide that deposits as senile plaques in Alzheimer's disease, is derived from the amyloid precursor protein (APP) by a gamma secretase-mediated intramembranous cleavage. In addition to amyloid-beta, this cleavage produces a carboxyl-terminal intracellular fragment which has an unknown function. The carboxyl-terminal domain of APP interacts in the cytoplasm with an adapter protein, Fe65. We demonstrate by laser scanning confocal microscopy that a gamma secretase generated APP carboxyl-terminal domain, tagged with green fluorescent protein (GFP), translocates to the nucleus in a manner dependent upon stabilization by the adapter protein Fe65; APP which has been mutated to block interactions with Fe65 cannot be detected in the nucleus. The APP-CT domain continues to interact with Fe65 in the nucleus, as determined by both colocalization and fluorescence resonance energy transfer (FRET). Visualization of the APP-CT-Fe65 complex in the nucleus may serve as a readout for processes that modify gamma secretase release of APP-CT. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Alzheimer Unit,Alzheimer Dis Res Lab, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Alzheimer Unit,Alzheimer Dis Res Lab, 114 16th St,CAGN 2009, Charlestown, MA 02129 USA. FU NIA NIH HHS [P01 AG15379, AG12406] NR 35 TC 74 Z9 77 U1 0 U2 0 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 AUG PY 2002 VL 82 IS 4 BP 839 EP 847 DI 10.1046/j.1471-4159.2002.01016.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 582UJ UT WOS:000177369300012 PM 12358789 ER PT J AU Davachi, L Wagner, AD AF Davachi, L Wagner, AD TI Hippocampal contributions to episodic encoding: Insights from relational and item-based learning SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MEDIAL TEMPORAL-LOBE; HUMAN-MEMORY FORMATION; PREFRONTAL CONTRIBUTIONS; COGNITIVE NEUROSCIENCE; RECOGNITION MEMORY; WORKING-MEMORY; BRAIN ACTIVITY; FMRI; RETRIEVAL; CORTEX AB The integrity of the hippocampus and surrounding medial-temporal cortices is critical for episodic memory, with the hippocampus being posited to support relational or configural associative learning. The present event-related functional magnetic resonance imaging (fMRI) study investigated the role of specific medial-temporal lobe structures in learning during relational and item-based processing, as well as the extent to which these structures are engaged during item-based maintenance of stimuli in working memory. fMRI indexed involvement of the hippocampus and underlying cortical regions during performance of two verbal encoding conditions, one that required item-based maintenance of word triplets in working memory and the other that entailed the formation of inter-item associations across the words in each triplet. Sixteen subjects were scanned using a rapid event-related fMRI design while they encountered the item-based and relational processing trials. To examine the correlation between fMRI signal in medial-temporal structures during learning and the subject's subsequent ability to remember the stimuli (a measure of effective memory formation), subjects were administered a yes-no recognition memory test following completion of the encoding scans. Results revealed that the hippocampus proper was engaged during both relational and item-based processing, with relational processing resulting in a greater hippocampal response. By contrast, entorhinal and parahippocampal gyri were differentially engaged during item-based processing, providing strong evidence for a functional neuroanatomic distinction between hippocampal and parahippocampal structures. Analysis of the neural correlates of subsequent memory revealed that activation in the bilateral hippocampus was reliably correlated with behavioral measures of effective memory formation only for those stimuli that were encoded in a relational manner. Taken together, these data provide evidence that the hippocampus, while engaged during item-based working memory maintenance, differentially subserves the relational binding of items into an integrated memory trace so that the experience can be later remembered. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Ctr Learning & Memory, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,MIT, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Davachi, L (reprint author), MIT, Dept Brain & Cognit Sci, NE-20,Rm 343, Cambridge, MA 02139 USA. FU NIMH NIH HHS [MH-12793, MH-60941] NR 67 TC 290 Z9 293 U1 1 U2 25 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2002 VL 88 IS 2 BP 982 EP 990 DI 10.1152/jn00046.2002 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 581DP UT WOS:000177276100039 PM 12163547 ER PT J AU Stasheff, SF Masland, RH AF Stasheff, SF Masland, RH TI Functional inhibition in direction-selective retinal ganglion cells: Spatiotemporal extent and intralaminar interactions SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID STARBURST AMACRINE CELLS; COMPLEX RECEPTIVE-FIELDS; RABBIT RETINA; VERTEBRATE RETINA; GABA(C) RECEPTORS; ACETYLCHOLINE-RELEASE; GLUTAMATE RECEPTORS; CHOLINERGIC NEURONS; ACTION-POTENTIALS; MAMMALIAN RETINA AB We recorded from ON-OFF direction-selective ganglion cells (DS cells) in the rabbit retina to investigate in detail the inhibition that contributes to direction selectivity in these cells. Using paired stimuli moving sequentially across the cells' receptive fields in the preferred direction, we directly confirmed the prediction of Wyatt and Daw (1975) that a wave of inhibition accompanies any moving excitatory stimulus on its null side, at a fixed spatial offset. Varying the interstimulus distance, stimulus size, luminance, and speed yielded a spatiotemporal map of the strength of inhibition within this region. This "null" inhibition was maximal at an intermediate distance behind a moving stimulus: 1/2 to 1 1/2 times the width of the receptive field. The strength of inhibition depended more on the distance behind the stimulus than on stimulus speed, and the inhibition often lasted 1-2 s. These spatial and temporal parameters appear to account for the known spatial frequency and velocity tuning of ON-OFF DS cells to drifting contrast gratings. Stimuli that elicit distinct ON and OFF responses to leading and trailing edges revealed that an excitatory response of either polarity could inhibit a subsequent response of either polarity. For example, an OFF response inhibited either an ON or OFF response of a subsequent stimulus. This inhibition apparently is conferred by a neural element or network spanning the ON and OFF sublayers of the inner plexiform layer, such as a multistratified amacrine cell. Trials using a stationary flashing spot as a probe demonstrated that the total amount of inhibition conferred on the DS cell was equivalent for stimuli moving in either the null or preferred direction. Apparently the cell does not act as a classic "integrate and fire" neuron, summing all inputs at the soma. Rather, computation of stimulus direction likely involves interactions between excitatory and inhibitory inputs in local regions of the dendrites. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Stasheff, SF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, 429 Wellman Bldg,50 Blossom St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS-01701-09] NR 66 TC 17 Z9 18 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 AUG PY 2002 VL 88 IS 2 BP 1026 EP 1039 DI 10.1152/jn01033.2001 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 581DP UT WOS:000177276100043 PM 12163551 ER PT J AU Kotilinek, LA Bacskai, B Westerman, M Kawarabayashi, T Younkin, L Hyman, BT Younkin, S Ashe, KH AF Kotilinek, LA Bacskai, B Westerman, M Kawarabayashi, T Younkin, L Hyman, BT Younkin, S Ashe, KH TI Reversible memory loss in a mouse transgenic model of Alzheimer's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; transgenic; behavior; A beta; monoclonal antibodies; memory ID BETA; IMMUNIZATION; PATHOLOGY; PLAQUES; BRAIN; MICE AB Alzheimer's disease (AD) is a neurodegenerative condition, believed to be irreversible, characterized by inexorable deterioration of memory and intellect, with neuronal loss accompanying amyloid plaques and neurofibrillary tangles. In an amyloid precursor protein transgenic mouse model, Tg2576, little or no neuronal loss accompanies age-related memory impairment or the accumulation of Abeta, a 40-42 aa polypeptide found in plaques. Recently, we have shown inverse correlations between brain Abeta and memory in Tg2576 mice stratified by age (Westerman et al., 2002). Broadening the age range examined obscured this relationship, leading us to propose that small, soluble assemblies of Abeta disrupt cognitive function in these mice. Here we show that memory loss can be fully reversed in Tg2576 mice using intraperitoneally administered BAM-10, a monoclonal antibody recognizing the N terminus of Abeta. The beneficial effect of BAM-10 was not associated with a significant Abeta reduction, but instead eliminated the inverse relationship between brain Abeta and memory. We postulate that BAM-10 acts by neutralizing Abeta assemblies in the brain that impair cognitive function. Our results indicate that a substantial portion of memory loss in Tg2576 mice is not permanent. If these Abeta assemblies contribute significantly to memory loss in AD, then successfully targeting them might improve memory in some AD patients. C1 Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp East, Dept Neurol, Charlestown, MA 02129 USA. Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. RP Ashe, KH (reprint author), Univ Minnesota, Dept Neurol, Mayo Mail Code 295,420 Delaware St SE, Minneapolis, MN 55455 USA. FU NIA NIH HHS [AG08687, AG15453]; NIMH NIH HHS [MH65465]; NINDS NIH HHS [NS33249] NR 13 TC 320 Z9 336 U1 1 U2 19 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 AUG 1 PY 2002 VL 22 IS 15 BP 6331 EP 6335 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 579MV UT WOS:000177182700006 PM 12151510 ER PT J AU Moore, KA Kohno, T Karchewski, LA Scholz, J Baba, H Woolf, CJ AF Moore, KA Kohno, T Karchewski, LA Scholz, J Baba, H Woolf, CJ TI Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuropathic pain; GAD; CCI; SNI; cell death; disinhibition ID ADULT-RAT; SUBSTANTIA-GELATINOSA; NEUROPATHIC PAIN; GLUTAMATE-DECARBOXYLASE; GABA-IMMUNOREACTIVITY; EVOKED ALLODYNIA; CELL-DEATH; RECEPTOR; NEURONS; TRANSMISSION AB To clarify whether inhibitory transmission in the superficial dorsal horn of the spinal cord is reduced after peripheral nerve injury, we have studied synaptic transmission in lamina II neurons of an isolated adult rat spinal cord slice preparation after complete sciatic nerve transection (SNT), chronic constriction injury (CCI), or spared nerve injury (SNI). Fast excitatory transmission remains intact after all three types of nerve injury. In contrast, primary afferent-evoked IPSCs are substantially reduced in incidence, magnitude, and duration after the two partial nerve injuries, CCI and SNI, but not SNT. Pharmacologically isolated GABA(A) receptor-mediated IPSCs are decreased in the two partial nerve injury models compared with naive animals. An analysis of unitary IPSCs suggests that presynaptic GABA release is reduced after CCI and SNI. Partial nerve injury also decreases dorsal horn levels of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) 65 kDa ipsilateral to the injury and induces neuronal apoptosis, detected by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining in identified neurons. Both of these mechanisms could reduce presynaptic GABA levels and promote a functional loss of GABAergic transmission in the superficial dorsal horn. C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Moore, KA (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA. EM Kohno@helix.mgh.harvard.edu FU NINDS NIH HHS [NS11076-01, R01 NS38253-01] NR 30 TC 458 Z9 483 U1 5 U2 36 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 AUG 1 PY 2002 VL 22 IS 15 BP 6724 EP 6731 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 579MV UT WOS:000177182700047 PM 12151551 ER PT J AU Benmansour, S Owens, WA Cecchi, M Morilak, DA Frazer, A AF Benmansour, S Owens, WA Cecchi, M Morilak, DA Frazer, A TI Serotonin clearance in vivo is altered to a greater extent by antidepressant-induced downregulation of the serotonin transporter than by acute blockade of this transporter SO JOURNAL OF NEUROSCIENCE LA English DT Article DE serotonin transporter; antidepressant; sertraline; chronoamperometry; downregulation; mRNA ID EXTRACELLULAR SEROTONIN; RAT-BRAIN; IN-VIVO; REUPTAKE INHIBITORS; MESSENGER-RNA; DOPAMINE; FLUOXETINE; RELEASE; 5-HYDROXYTRYPTAMINE; DESENSITIZATION AB Serotonin uptake, mediated by the serotonin transporter (SERT), is blocked acutely by antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), but such blockade does not correlate temporally with the onset of therapeutic improvement. Treatment with SSRIs for 21 d induced downregulation of the SERT (Benmansour et al., 1999). The time course of SERT downregulation as well as the time course for its recovery after cessation of treatment with the SSRI sertraline were investigated using tritiated cyanoimipramine to measure SERT binding sites. To determine if there was a temporal correlation between the time when sertraline induced downregulation of the SERT and when marked alteration in SERT function occurred, clearance of locally applied 5-HT into the CA3 region of hippocampus was achieved using in vivo electrochemistry. After 4 or 10 d treatment with sertraline, SERT binding sites decreased very little (15-30%), and the chronoamperometric signals for serotonin in sertraline-treated rats were comparable with ones obtained in control animals. By contrast, after 15 d of treatment, when SERT binding sites were markedly reduced by 80%, there was robust decrease in the clearance of 5-HT. Moreover, the functional consequences of SERT downregulation as measured by chronoamperometry were significantly greater than those seen after acute blockade of the SERT by SSRIs. SERT binding sites decreases are not a consequence of reduced SERT gene expression, as revealed by in situ hybridization measurements. SSRI-induced downregulation of the SERT may be a key component for the clinical response to SSRIs. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Benmansour, S (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIMH NIH HHS [MH53851, MH57001] NR 42 TC 123 Z9 123 U1 0 U2 6 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 AUG 1 PY 2002 VL 22 IS 15 BP 6766 EP 6772 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 579MV UT WOS:000177182700052 PM 12151556 ER PT J AU Starr, PA Christine, CW Theodosopoulos, PV Lindsey, N Byrd, D Mosley, A Marks, WJ AF Starr, PA Christine, CW Theodosopoulos, PV Lindsey, N Byrd, D Mosley, A Marks, WJ TI Implantation of deep brain stimulators into the subthalamic nucleus: technical approach and magnetic resonance imaging-verified lead locations SO JOURNAL OF NEUROSURGERY LA English DT Article DE subthalamic nucleus; deep brain stimulation; Parkinson disease; microelectrode recording; magnetic resonance imaging; surgical approach ID ADVANCED PARKINSONS-DISEASE; CHRONIC ELECTRICAL-STIMULATION; VENTRALIS INTERMEDIUS NUCLEUS; GLOBUS-PALLIDUS; MOVEMENT-DISORDERS; SUBSTANTIA-NIGRA; LOCALIZATION; THALAMUS; PRIMATE; ELECTRODES AB Object. Chronic deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a procedure that is rapidly gaining acceptance for the treatment of symptoms in patients with Parkinson disease (PD), but there are few detailed descriptions of the surgical procedure itself. The authors present the technical approach used to implant 76 stimulators into the STNS of patients with PD and the lead locations, which were verified on postoperative magnetic resonance (MR) images. Methods. Implantation procedures were performed with the aid of stereotactic MR imaging, microelectrode recording (MER) in the region of the stereotactic target to define the motor area of the STN, and intraoperative test stimulation to assess the thresholds for stimulation-induced adverse effects. All patients underwent postoperative MR imaging, which was performed using volumetric gradient-echo and T-2-weighted fast-spin echo techniques, computational reformatting of the MR image into standard anatomical planes, and quantitative measurements of lead location with respect to the midcommissural point and the red nucleus. Lead locations were statistically correlated with physiological data obtained during MER and intraoperative test stimulation. Conclusions. The authors' approach to implantation of DBS leads into the STN was associated with consistent lead placement in the dorsolateral STN, a low rate of morbidity, efficient use of operating room time, and robust improvement in motor function. The mean coordinates of the middle of the electrode array, measured on postoperative MR images, were 11.6 mm lateral, 2.9 mm posterior, and 4.7 mm inferior to the midcommissural point, and 6.5 mm lateral and 3.5 mm anterior to the center of the red nucleus. Voltage thresholds for several types of stimulation-induced adverse effects were predictive of lead location. Technical nuances of the surgery are described in detail. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Nursing, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Dept Neurol, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, Dept Nursing, San Francisco, CA USA. RP Starr, PA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, Moffitt Hosp 779, 505 Parnassus Ave, San Francisco, CA 94143 USA. NR 57 TC 278 Z9 286 U1 2 U2 12 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2002 VL 97 IS 2 BP 370 EP 387 DI 10.3171/jns.2002.97.2.0370 PG 18 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 582LP UT WOS:000177352700019 PM 12186466 ER PT J AU Okano, M Li, E AF Okano, M Li, E TI Genetic analyses of DNA methyltransferase genes in mouse model system SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Trans-HHS Workshop on Diet, DNA Methylation Processes and Health CY AUG 06-08, 2001 CL BETHESDA, MARYLAND SP Natl Ctr Toxicol Res, Food & Durg Adm, Ctr Canc Res, Div Canc Prevent, NHLBI, NICHHD, NIDDK, NIEHS, Div Nutrit Res Coordinat, Off Dietary Supplements, Amer Soc Nutrit Sci, Int Life Sci Inst N Amer DE DNA methylation; Dnmt1; Dnmt3a; Dnmt3b; ES cells; knockout mouse ID EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; CYTOSINE-5 METHYLTRANSFERASES; IMMUNODEFICIENCY SYNDROME; MAMMALIAN DEVELOPMENT; IN-VIVO; DNMT3A; CANCER; (CYTOSINE-5)-METHYLTRANSFERASE; TRANSCRIPTION AB DNA methylation regulates important biological processes and is involved in tumorigenesis and several human diseases, such as Rett and immunodeficiency, centromeric instability and facial anomalies (ICF). The major objective of our research is to investigate the roles of DNA methylation in mammals through genetic analysis of DNA methyltransferase genes in mouse and human. Previously, we found that Dnmt1 knockout embryonic stem (ES) cells are capable of methylating retroviral DNA de novo. In search of enzymes responsible for de novo methylation, we have cloned a novel family of mammalian DNA methyltransferase genes, Dnmt3a and Dnmt3b. Although extensive sequence similarity was found between Dnmt3a and Dnmt3b, little homology was observed between Dnmt1 and Dnmt3a/3b in the catalytic domain as well as in the N-terminal domain. Additionally, biochemical analysis revealed that, unlike Dnmt1, neither Dnmt3a nor Dnmt3b had a strong preference to hemimethylated DNA substrates. Genetic analysis demonstrated that Dnmt3a and Dnmt3b were required for de novo methylation activities in ES cells and during early embryogenesis and were essential for early development. Interestingly, phenotype analyses of single homozygous mice for either Dnmt3a or Dnmt3b suggested that the functions of Dnmt3a and Dnmt3b also were required at the late developmental stage and even at the adult stage. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. RIKEN, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan. RP Okano, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA82389]; NIGMS NIH HHS [GM52106] NR 39 TC 20 Z9 25 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2002 VL 132 IS 8 SU S BP 2462S EP 2465S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 583GH UT WOS:000177398500027 PM 12163712 ER PT J AU John, DS Mulliken, JB Kaban, LB Padwa, BL AF John, DS Mulliken, JB Kaban, LB Padwa, BL TI Anthropometric analysis of mandibular asymmetry in infants with deformational posterior plagiocephaly SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DIFFERENTIAL-DIAGNOSIS; ORTHOTIC CRANIOPLASTY; SYNOSTOSIS AB Purpose: The incidence of deformational posterior plagiocephaly has increased dramatically since 1992. We tested the hypothesis that mandibular asymmetry, associated with this condition, is secondary to anterior displacement of the ipsilateral temporomandibular joint. The response to molding helmet therapy was also evaluated. Patients and Methods: A caliper was used to measure mandibular dimensions in 27 infants (16 boys and 11 girls) with deformational posterior plagiocephaly; the mean age was 6.2 months (range, 3 to 12 months). Anthropometric measures included ramal height (condylion-gonion), body length (gonion-gnathion), and condylion-gnathion. Gonial angle was calculated from the law of cosines: C-2 = A(2) + B-2 - 2AB cos c. The position of the temporomandibular joint was accepted as corresponding to auricular position and measured from tragion to subnasal. Cranial asymmetry was measured, in the horizontal plane, from orbitale superius to the contralateral parieto-occipital point at the level of inion. Ten of 27 patients were remeasured 5 months after beginning helmet therapy to evaluate change in mandibular dimensions. Results: Two thirds of infants (67%) had right-sided and one third (33%) had left-sided deformational posterior plagiocephaly. The mean auricular anterior displacement was 79.7 mm on the affected side and 83.4 mm on the unaffected side. The mean difference of 3.8 mm between the sides was statistically significant (P < .001). Transverse cranial dimension averaged 136.0 mm on the affected side and 146.8 mm on the unaffected side; this was also significant (P < .001). There was a significant positive correlation between auricular displacement and cranial asymmetry [R(23) = .59, P < .01). Auricular (temporomandibular joint) displacement also resulted in an apparent mandibular asymmetry with rotation of the jaw to the affected side. Mean mandibular measurements on the affected and unaffected sides were ramus height of 35.2 and 36.4 mm, body length of 59.0 and 60.3 mm, and gonial angle of 127.1degrees and 126.8degrees, respectively. Comparison of the affected with the unaffected sides, using a paired-samples t test, was not statistically significant. Improvement in cranial asymmetry occurred with helmet therapy, but there was no correction of auricular and temporomandibular joint position. Conclusions: This study supports the clinical observation that the mandibular asymmetry in deformational posterior plagiocephaly is secondary to rotation of the cranial base and anterior displacement of the temporomandibular joint (quantified by anterior auricular position) and not the result of primary mandibular deformity. (C) 2002 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Childrens Hosp, Div Oral & Maxillofacial Surg, Craniofacial Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Padwa, BL (reprint author), Childrens Hosp, Div Oral & Maxillofacial Surg, Craniofacial Ctr, 300 Longwood Ave, Boston, MA 02115 USA. NR 18 TC 3 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2002 VL 60 IS 8 BP 873 EP 877 DI 10.1053/jams.2002.33855 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 582BF UT WOS:000177329300007 ER PT J AU Todd, R AF Todd, R TI Effects of exogenous nitric oxide on oral squamous cell carcinoma: An in vitro study SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID APOPTOSIS; BIOLOGY; CANCER C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Todd, R (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, 188 Longwood Ave, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2002 VL 60 IS 8 BP 910 EP 911 DI 10.1053/jams.2002.33861 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 582BF UT WOS:000177329300014 ER PT J AU Kim, Y Donoff, RB Wong, DTW Todd, R AF Kim, Y Donoff, RB Wong, DTW Todd, R TI The nucleotide: DNA sequencing and its clinical application SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID CELL CARCINOMA SYNDROME; GORLIN SYNDROME; GENE; POLYMORPHISM; CHROMOSOME; MUTATIONS; CANCER AB Information determining cellular structure and function is contained in chromosomal DNA. Genes, regions of DNA encoding this information, are composed of specific sequences of nucleotides. DNA sequencing methods have been developed to identify these sequences. Even subtle alteration (or mutation) of these sequences can lead to many human syndromes and diseases. This article reviews 1) the structure of the nucleotide, 2) the methods of DNA sequencing, and 3) its recent clinical application in analysis of the nevoid basal cell carcinoma syndrome. (C) 2002 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Dent, Dept Oral Pathol, Los Angeles, CA 90024 USA. RP Todd, R (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, 188 Longwood Ave, Boston, MA 02115 USA. NR 26 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 2002 VL 60 IS 8 BP 924 EP 930 DI 10.1053/jams.2002.33864 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 582BF UT WOS:000177329300017 PM 12149740 ER PT J AU Bovasso, GB Alterman, AI Cacciola, JS Rutherford, MJ AF Bovasso, GB Alterman, AI Cacciola, JS Rutherford, MJ TI The prediction of violent and nonviolent criminal behavior in a methadone maintenance population SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID ANTISOCIAL PERSONALITY-DISORDER; OBJECT RELATIONS; GENDER-DIFFERENCES; SUBSTANCE-ABUSE; DSM-IV; EMPATHY; SCHIZOPHRENIA; RECIDIVISM; VALIDITY AB The utility of traits associated with Antisocial Personality Disorder in making risk assessments of violent and nonviolent crimes was examined in 254 subjects sampled from a methadone maintenance population. A factor analysis of a number of baseline measures resulted in five factors measuring hostility, insecure attachment, impaired reality testing, antisocial personality, and empathy. These factors were used in logistic regression analysis to predict charges for violent and nonviolent crimes over a 2-year period. Individuals with high scores on the antisocial personality factor had an increased risk of both violent and nonviolent criminal charges. Individuals with low scores on the empathy factor were at high risk for violent crimes. In an analysis using the factor components rather than the factors, the measures of perspective-taking and asocialization were associated with violent criminal charges, and the measure of psychopathy, but not antisocial behavior, was associated with nonviolent criminal charges. The results support the use of measures of personality traits in addition to measures of a history of antisocial behavior in making violence risk assessments in substance-dependent patients. The DSM construct and diagnosis of Antisocial Personality Disorder may be enhanced by greater emphasis on personality traits associated with antisocial behavior. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Washington, Seattle, WA 98195 USA. RP Bovasso, GB (reprint author), 850 W Church Rd, Elkins Pk, PA 19027 USA. EM g.bovasso@worldnet.att.net FU NIDA NIH HHS [DA05186]; PHS HHS [D-05858] NR 42 TC 19 Z9 20 U1 2 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD AUG PY 2002 VL 16 IS 4 BP 360 EP 373 DI 10.1521/pedi.16.4.360.24124 PG 14 WC Psychiatry SC Psychiatry GA 589JG UT WOS:000177754700006 PM 12224128 ER PT J AU Butterfield, RM Lewis, MA AF Butterfield, RM Lewis, MA TI Health-related social influence: A social ecological perspective on tactic use SO JOURNAL OF SOCIAL AND PERSONAL RELATIONSHIPS LA English DT Article DE health behaviors; influence tactics; marriage ID POWER STRATEGIES; PERSONAL RELATIONSHIPS; INTIMATE-RELATIONSHIPS; MARITAL SATISFACTION; PERSUASION SCHEMA; GENDER; BEHAVIOR; IMPACT; SCALE; GOALS AB The present study investigated predictors of health-related social influence tactic use in close relationships. According to the social ecological perspective, predictors were classified as reflecting characteristics of the agent of social influence, characteristics of the target of social influence, characteristics of the agent and target's relationship, and characteristics of the social influence situation. One hundred and nine married couples reported on situations in which each partner was attempting to influence his or her spouse to change a health-related behavior. Using the actor-partner interdependence analysis approach, results revealed only actor effects for characteristics of the agent, primarily partner effects for characteristics of the target, and both actor and partner effects for characteristics of the situation when predicting health-related tactic use. Effects for relationship characteristics only emerged in interactions with respondent sex. These results indicate that social influence in marriage involves reciprocity and interdependence. The importance of examining the dyadic nature of health-related social influence in close relationships is also highlighted. C1 Univ Colorado, Boulder, CO 80309 USA. Univ N Carolina, Chapel Hill, NC USA. RP Butterfield, RM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. NR 39 TC 48 Z9 48 U1 2 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0265-4075 J9 J SOC PERS RELAT JI J. Soc. Pers. Relatsh. PD AUG PY 2002 VL 19 IS 4 BP 505 EP 526 DI 10.1177/0265407502019004050 PG 22 WC Communication; Family Studies; Psychology, Social SC Communication; Family Studies; Psychology GA 588JQ UT WOS:000177698700004 ER PT J AU Fisher, JC Kling, DE Kinane, TB Schnitzer, JJ AF Fisher, JC Kling, DE Kinane, TB Schnitzer, JJ TI Oxidation-reduction (redox) controls fetal hypoplastic lung growth SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Association-for-Academic-Surgery CY NOV 15-17, 2001 CL MILWAUKEE, WISCONSIN SP Assoc Acad Surg DE pulmonary hypoplasia; antioxidants; congenital diaphragmatic hernia; fetal lung growth ID CONGENITAL DIAPHRAGMATIC-HERNIA; BIOCHEMICAL IMMATURITY; PULMONARY IMMATURITY; THERAPY IMPROVES; SHEEP; RATS AB Introduction. The persistent morbidity and mortality of congenital diaphragmatic hernia are largely due to associated pulmonary hypoplasia. We have shown previously that three antioxidants (vitamin C, glutathione, and vitamin E) could accelerate the growth of fetal hypoplastic lungs grown in culture. We hypothesize that this occurs via a reductant mechanism. Methods. Timed-pregnant rats were gavage-fed nitrofen (100 mg) on day 9.5 of gestation (term = day 22). Fetal lungs were harvested on day 13.5 and placed in organ culture containing serum-free BGJb medium with antibiotics. After randomization, the lung organ cultures were divided into a control group (n = 31) and an experimental group that received the antioxidant N-acetylcysteine (NAC, 100 muM, n = 31). The fetal lung organ cultures were grown for 4 days at 37degreesC with 5% CO. Computer-assisted digital tracings of the airways were performed daily on live, unstained specimens, and lung bud count, perimeter, and area were measured. After 4 days, lungs were pooled, homogenized, and assayed for reduced and oxidized glutathione, normalized to protein, as an estimate of the tissue redox potential. Data were expressed as means +/- SEM, and statistical comparisons were performed using Student's unpaired t test, with P < 0.05 considered significant. Results. Area, perimeter, lung bud count, and complexity (as measured by the perimeter/square root of area) were all significantly increased with NAC treatment from day 2 onward. Reduced glutathione levels were significantly increased following NAC administration (67.1 +/- 5.8 versus 37.5 +/- 4.2 μmol/mg, P = 0.0004). The ratio of reduced to oxidized glutathione was 2.23. Conclusions. N-Acetylcysteine stimulates nitrofeninduced hypoplastic fetal lung growth in organ culture and increases the ratio of reduced to oxidized glutathione. These data support the concept that oxidation-reduction (redox) may be an important control mechanism for fetal lung growth. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Dept Surg,Pediat Surg Res Labs, Boston, MA 02114 USA. RP Fisher, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Dept Surg,Pediat Surg Res Labs, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03132] NR 22 TC 25 Z9 26 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2002 VL 106 IS 2 BP 287 EP 291 DI 10.1006/jsre.2002.6461 PG 5 WC Surgery SC Surgery GA 592BY UT WOS:000177917900010 PM 12175980 ER PT J AU Saliba, D Schnelle, JF AF Saliba, D Schnelle, JF TI Indicators of the quality of nursing home residential care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 17-21, 2000 CL NASHVILLE, TENNESSEE SP Amer Geriatr Soc DE quality; nursing home; care processes; staff; activities of daily living; preferences ID LONG-TERM-CARE; ASSESSMENT INSTRUMENT; OF-LIFE; CAROTID ENDARTERECTOMY; CORONARY-ANGIOGRAPHY; URINARY-INCONTINENCE; THERAPEUTIC DESIGN; SOCIAL ENGAGEMENT; PHYSICAL-ACTIVITY; RANDOMIZED TRIAL AB OBJECTIVES: To identify quality indicators (QIs) that can be used to measure nursing home (NH) residential care processes. DESIGN: Modified-delphi panel process to rate potential QIs that were identified through reported interviews with residents and families and through a review of the scientific literature. SETTING: Meetings of panel of experts. PARTICIPANTS: A national panel of nine experts in NH care rated potential QIs. A content expert and a clinical oversight committee performed external reviews. MEASUREMENTS: Panelists' median validity and importance ratings for each QI choice. RESULTS: The panel considered 64 choices for QI content and rated 28 of these as valid and important for measuring residential care quality. These 28 choices translated into 18 QIs. The external review process resulted in the addition of one QI that was not considered by the NH panel. The 19 indicators address areas identified as important by residents and proxies. Ten of these QIs were rated feasible to implement with current resources in average community NHs, and nine were rated feasible only in better NHs. The panelists identified nine as being measured most reliably by direct observations of care. CONCLUSION: Experts identified 19 specific care processes as valid and important measures of the quality of NH residential care. Nine of these QIs may be measured best by direct observation of NH care, rather than by interviews or review of existing NH records. Almost half of the QIs were viewed as discriminating between better and average NHs. The panel deemed that only well-staffed nursing homes could consistently implement nine of the QIs. C1 RAND Corp, Santa Monica, CA 90401 USA. VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Univ Calif Los Angeles, Multicampus Program Geriatr, Los Angeles, CA USA. Univ Calif Los Angeles, Borun Ctr Gerontol Res, Los Angeles, CA USA. RP Saliba, D (reprint author), RAND Corp, 1700 Main St, Santa Monica, CA 90401 USA. FU NIA NIH HHS [AG10415] NR 86 TC 36 Z9 36 U1 1 U2 7 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 AUG PY 2002 VL 50 IS 8 BP 1421 EP 1430 DI 10.1046/j.1532-5415.2002.50366.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 580VD UT WOS:000177256200016 PM 12165001 ER PT J AU Miyamoto, MI Picard, MH AF Miyamoto, MI Picard, MH TI Left atrial mass caused by metastatic renal cell carcinoma: An unusual site of tumor involvement mimicking myxoma SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article AB We report a case of a left atrial mass echocardiographically mimicking myxoma, in a patient with renal cell carcinoma. The mass was pathologically confirmed to be metastatic carcinoma, which had entered the left atrium from a mediastinal lymph node, via direct invasion of a pulmonary vein, illustrating the potential for unusual routes of tumor spread into the heart and the importance of obtaining a tissue diagnosis in such cases. C1 Mission Internal Med Grp, Mission Cardiol Heart Failure Program, Mission Viejo, CA USA. Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Miyamoto, MI (reprint author), 26732 Crown Valley Pkwy,Suite 161, Mission Viejo, CA 92691 USA. OI Picard, Michael/0000-0002-9264-3243 NR 3 TC 3 Z9 3 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 AUG PY 2002 VL 15 IS 8 BP 847 EP 848 DI 10.1067/mje.2002.120508 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 583VT UT WOS:000177431800016 PM 12174358 ER PT J AU Moses, AV Jarvis, MA Raggo, C Bell, YC Ruhl, R Luukkonen, BGM Griffith, DJ Wait, CL Druker, BJ Heinrich, MC Nelson, JA Fruh, K AF Moses, AV Jarvis, MA Raggo, C Bell, YC Ruhl, R Luukkonen, BGM Griffith, DJ Wait, CL Druker, BJ Heinrich, MC Nelson, JA Fruh, K TI Kaposi's sarcoma-associated herpesvirus-induced upregulation of the c-kit proto-oncogene, as identified by gene expression profiling, is essential for the transformation of endothelial cells SO JOURNAL OF VIROLOGY LA English DT Review ID TYROSINE KINASE INHIBITOR; GASTROINTESTINAL STROMAL TUMORS; PRIMARY-EFFUSION LYMPHOMA; MULTICENTRIC CASTLEMANS-DISEASE; HEMATOPOIETIC PROGENITOR CELLS; EPSTEIN-BARR-VIRUS; GROWTH-FACTOR; SPINDLE CELLS; HUMAN CYTOMEGALOVIRUS; COUPLED RECEPTOR AB Kaposi's sarcoma (KS), the most frequent malignancy afflicting AIDS patients, is characterized by spindle cell formation and vascularization. Infection with KS-associated herpesvirus (KSHV) is consistently observed in all forms of KS. Spindle cell formation can be replicated in vitro by infection of dermal microvascular endothelial cells (DMVEC) with KSHV. To study the molecular mechanism of this transformation, we compared RNA expression profiles of KSHV-infected and mock-infected DMVEC. Induction of several protooncogenes was observed, particularly the receptor tyrosine kinase c-kit. Consistent with increased c-Kit expression, KHSV-infected DMVEC displayed enhanced proliferation in response to the c-Kit ligand, stem cell factor (SCF). Inhibition of e-Kit activity with either a pharmacological inhibitor of c-Kit (STI 571) or a dominant-negative c-Kit protein reversed SCF-dependent proliferation. Importantly, inhibition of c-Kit signal transduction reversed the KSHV-induced morphological transformation of DMVEC. Furthermore, overexpression studies showed that c-Kit was sufficient to induce spindle cell formation. Together, these data demonstrate an essential role for c-Kit in KS tumorigenesis and reveal a target for pharmacological intervention. C1 Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RW Johnson Pharmaceut Res Inst, San Diego, CA 92121 USA. RP Moses, AV (reprint author), 505 NW 185th Ave, Beaverton, OR 97006 USA. FU NCRR NIH HHS [K01 RR000163, P51 RR000163] NR 116 TC 98 Z9 102 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 AUG PY 2002 VL 76 IS 16 BP 8383 EP 8399 DI 10.1128/JVI.76.16.8383.8399.2002 PG 17 WC Virology SC Virology GA 577EX UT WOS:000177049500047 PM 12134042 ER PT J AU O'Brien, MM Gonzales, R Shroyer, AL Grunwald, GK Daley, J Henderson, WG Khuri, SF Anderson, RJ AF O'Brien, MM Gonzales, R Shroyer, AL Grunwald, GK Daley, J Henderson, WG Khuri, SF Anderson, RJ TI Modest serum creatinine elevation affects adverse outcome after general surgery SO KIDNEY INTERNATIONAL LA English DT Article DE creatinine; postoperative mortality; morbidity; surgery risk factors; preoperative assessment ID MAJOR NONCARDIAC SURGERY; AFFAIRS SURGICAL RISK; RENAL-FAILURE; CARDIAC RISK; QUALITY; CARE; ADJUSTMENT; PREDICTION; INSUFFICIENCY; POPULATION AB Background. Modest preoperative serum creatinine elevation (1.5 to 3.0 mg/dL) has been recently shown to be independently associated with morbidity and mortality after cardiac surgery. It is important to know if this association can be applied more broadly to general surgery cases. Methods. Multivariable logistic regression analyses of 46 risk variables in 49,081 cases from the Veterans Affairs National Surgical Quality Improvement Program, undergoing major general surgery from 10/1/96 through 9/30/98. Results. Thirty day mortality and several cardiac, respiratory, infectious and hemorrhagic morbidities were significantly (P < 0.001) higher in patients with a serum creatinine>1.5 mg/dL. With multivariable analysis, the adjusted odds ratio for mortality for patients with a serum creatinine of 1.5 to 3.0 mg/dL was 1.44 [95% confidence interval (95% CI) 1.22 to 1.71] and for creatinine>3.0 mg/dL was 1.93 (95% CI 1.51 to 2.46). The adjusted odds ratio for morbidity (one or more postoperative complications) for patients with a serum creatinine of 1.5 to 3.0 mg/dL was 1.18 (95% CI 1.06 to 1.32) and for creatinine>3.0 mg/dL was 1.19 (95% CI 0.99 to 1.43). Further stratification and recursive partitioning of creatinine levels revealed that a serum creatinine level>1.5 mg/dL was the approximate threshold for both increased morbidity and mortality. Conclusions. Modest preoperative serum creatinine elevation (>1.5 mg/dL) is a significant predictor of risk-adjusted morbidity and mortality after general surgery. A preoperative serum creatinine of 1.5 mg/dL or higher is a readily available marker for potential adverse outcomes after general surgery. C1 Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Div Cardiac Res, Denver, CO USA. RP Anderson, RJ (reprint author), Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Campus Box B180,4200 E 9th Ave, Denver, CO 80262 USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 31 TC 55 Z9 56 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 2002 VL 62 IS 2 BP 585 EP 592 DI 10.1046/j.1523-1755.2002.00486.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 571YK UT WOS:000176746600026 PM 12110022 ER PT J AU Busaba, NY Kieff, D AF Busaba, NY Kieff, D TI Endoscopic sinus surgery for inflammatory maxillary sinus disease SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Annual Meeting of the Eastern Section of the Triological-Society CY JAN 25-27, 2001 CL PHILADELPHIA, PENNSYLVANIA DE maxillary sinus mucocele; retention cyst; antrochoanal polyp; Caldwell Luc; endoscopic sinus surgery ID SURGICAL-TREATMENT; NASAL; MUCOCELES AB Objective/Hypothesis: The role of endoscopic sinus surgery for treating chronic maxillary sinusitis is well established. The purpose of the study is to determine the efficacy of endoscopic sinus surgery in the treatment of maxillary sinus inflammatory disease that includes mucoceles, retention cysts, and antrochoanal polyps. Study Design: This is a retrospective review of 32 consecutive patients who underwent endoscopic sinus surgery for mucoceles (n = 21), retention cysts (n = 5), or antrochoanal polyps (n = 6). Methods: The medical records were reviewed for patient demographics, presenting symptoms, and type of operation. Surgical outcome was determined by resolution of symptoms, recurrence of disease, and need for revision or additional surgery. Results: Ethmoidectomy with middle meatal antrostomy was performed in all patients; 28 patients had additional middle turbinectomy. Postoperative follow-up ranged from 6 months to 4 years. The operation resulted in resolution of symptoms and a patent antrostomy on long-term follow-up in all cases of mucoceles. No case required revision surgery. On the other hand, the disease recurred in three patients (60%) with retention cysts and three patients (50%) with antrochoanal polyps despite patent antrostomies. The recurrences occurred 3 to 6 months after the surgery. The recurrent cases of antrochoanal polyps required Caldwell Luc procedures. The three failures in cases of retention cysts were successfully managed with repeated office endoscopic marsupialization through a patent antrostomy. Conclusions: Endoscopic sinus surgery is an effective treatment for mucoceles, with favorable long-term outcome. Maxillary retention cysts commonly recur after endoscopic sinus surgery. However, the recurrence can be managed in the office through a patent antrostomy. Endoscopic sinus surgery may be offered as initial surgical treatment for antrochoanal polyps, but a Caldwell Luc operation may be needed for recurrent disease. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Vet Affairs Boston Hlth Care Syst, Div Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 16 TC 19 Z9 23 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 AUG PY 2002 VL 112 IS 8 BP 1378 EP 1383 DI 10.1097/00005537-200208000-00010 PN 1 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 581JU UT WOS:000177289300010 PM 12172248 ER EF